Publications by authors named "Jason Jungsik Song"

116 Publications

Clinical significance of large unstained cell count in estimating the current activity of ANCA-associated vasculitis.

Int J Clin Pract 2021 Jun 12:e14512. Epub 2021 Jun 12.

Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.

Background: We investigated whether large unstained cell (LUC) count could estimate the current high activity according to Birmingham vasculitis activity score (BVAS) in patients with antineutrophil cytoplasmic antibody (ANCA) positive ANCA-associated vasculitis (AAV).

Methods: We retrospectively reviewed the medical records of 176 immunosuppressive drug-naïve patients with ANCA positive AAV. Clinical and laboratory data at diagnosis, including LUC count, were collected. High BVAS was defined as the highest tertile of BVAS (BVAS ≥ 15) in this study.

Results: The median age was 61.0 years and 64.8% were female. The median LUC count was 60.0/mm and LUC was detected in 106 patients. LUC count was significantly correlated with BVAS, age, white blood cell count, haemoglobin, platelet count, serum albumin, erythrocyte sedimentation rate and C-reactive protein. Overall, the median BVAS in AAV patients with LUC positivity was significantly higher than that in those without (14.0 vs. 10.0). When the cut-off of LUC count for the current high BVAS was set as BVAS ≥ 15/mm , AAV patients with LUC count ≥ 15/mm had a significantly higher risk for the current high BVAS than those with LUC count < 15/mm (relative risk 2.596). However, in the multivariable linear and logistic regression analyses, LUC did not seem to estimate the current BVAS independently among clinical and laboratory variables.

Conclusion: LUC count was significantly correlated with the current BVAS and LUC count ≥ 15/mm could estimate the current high BVAS in patients with ANCA positive AAV.
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http://dx.doi.org/10.1111/ijcp.14512DOI Listing
June 2021

The Efficacy of Mycophenolate Mofetil in Remission Maintenance Therapy for Microscopic Polyangiitis and Granulomatosis with Polyangiitis.

Yonsei Med J 2021 Jun;62(6):494-502

Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.

Purpose: The present study compared the efficacy of mycophenolate mofetil (MMF) with that of azathioprine (AZA) in Korean patients with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA).

Materials And Methods: The medical records of 69 patients with MPA and GPA who received cyclophosphamide and subsequently received AZA or MMF for remission maintenance therapy were reviewed. All-cause mortality, relapse, end-stage renal disease (ESRD), cerebrovascular accident, and cardiovascular disease were evaluated as poor outcomes. Having a lower Birmingham Vasculitis Activity Score (BVAS) was defined as the lowest tertile of BVAS (BVAS ≤11 in this study).

Results: In comparative analysis of the occurrence of poor outcomes among patients taking AZA only, MMF only, and MMF after AZA, patients taking MMF only exhibited a significantly lower cumulative ESRD-free survival rate than patients taking AZA only (=0.028). In terms of ESRD occurrence between the groups based on BVAS at diagnosis, among patients with MPA and GPA with higher BVAS at diagnosis, patients taking MMF only exhibited a significantly lower cumulative ESRD-free survival rate than those taking AZA only (=0.047). Among patients with MPA and GPA with the lowest tertile of BVAS at diagnosis, cumulative ESRD-free survival rates did not differ.

Conclusion: With regard to ESRD occurrence, the efficacy of MMF in remission maintenance therapy was less effective than AZA in patients with MPA and GPA. However, among patients with lower BVAS, there was no difference in the occurrence of poor outcomes between patients taking MMF and those taking AZA.
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http://dx.doi.org/10.3349/ymj.2021.62.6.494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8149928PMC
June 2021

Association between follistatin-related protein 1 and the functional status of patients with anti-neutrophil cytoplasmic antibody-associated vasculitis.

Chin Med J (Engl) 2021 Apr 14;134(10):1168-1174. Epub 2021 Apr 14.

Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.

Background: Follistatin-like 1 (FSTL1) plays both pro-inflammatory and anti-inflammatory roles in the inflammatory processes. We investigated whether serum FSTL1 could predict the current anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV)-specific indices.

Methods: We randomly selected 74 patients with AAV from a prospective and observational cohort of Korean patients with AAV. Clinical and laboratory data and AAV-specific indices were recorded. FSTL1 concentration was determined using the stored sera. The lowest tertile of the short-form 36-item health survey (SF-36) was defined as the current low SF-36. The cutoffs of serum FSTL1 for the current low SF-36 physical component summary (PCS) and SF-36 mental component summary (MCS) were extrapolated by the receiver operator characteristic curve.

Results: The median age was 62.5 years (55.4% were women). Serum FSTL1 was significantly correlated with SF-36 PCS (r =  - 0.374), SF-36 MCS (r = -0.377), and C-reactive protein (CRP) (r = 0.307), but not with Birmingham vasculitis activity score (BVAS). In the multivariable linear regression analyses, BVAS, CRP, and serum FSTL1 were independently associated with the current SF-36 PCS (β = -0.255, β = -0.430, and β = -0.266, respectively) and the current SF-36 MCS (β = -0.234, β =-0.229, and β = -0.296, respectively). Patients with serum FSTL1 ≥779.8 pg/mL and those with serum FSTL1 ≥841.6 pg/mL exhibited a significantly higher risk of having the current low SF-36 PCS and SF-36 MCS than those without (relative risk 7.583 and 6.200, respectively).

Conclusion: Serum FSTL1 could predict the current functional status in AAV patients.
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http://dx.doi.org/10.1097/CM9.0000000000001454DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8143737PMC
April 2021

Serum galectin-9 could be a potential biomarker in assessing the disease activity of antineutrophil cytoplasmic antibody-associated vasculitis.

Clin Exp Rheumatol 2021 May 10. Epub 2021 May 10.

Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, and Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul, Republic of Korea.

Objectives: Serum galectin levels have been reported to be associated with the activity in autoimmune diseases. This study investigated whether serum levels of galectin (Gal)-1, Gal-3, and Gal-9 could be used as biomarkers in assessing the disease activity of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).

Methods: Eighty AAV patients were selected for inclusion in our AAV cohort. AAV-specific indices and clinical and laboratory data were assessed on the same day when blood samples were obtained from the patient and serum levels of Gal-1, Gal-3, and Gal-9 were measured by ELISA from obtained sera. High disease activity was defined as Birmingham vasculitis activity score (BVAS) ≥ 12. The optimal cut-off value of galectins was extrapolated by receiver operator characteristic analysis and linear and logistic regression analyses were performed to evaluate the association between Gal-3, Gal-9, and BVAS.

Results: The median values of BVAS, Gal-1, Gal-3, and Gal-9 were 8.0, 38.1 ng/mL, 12.4 ng/mL, and 1017.7 ng/mL, respectively. Serum Gal-3 and Gal-9 levels were correlated with BVAS (r=0.375 and r=0.462), while only serum Gal-9 levels were independently associated with BVAS (β=0.250) in linear regression analyses. Serum Gal-9 ≥10.28 ng/mL was also associated with high activity of AAV (odds ratio 5.303) in multivariable logistic regression analysis. In addition, serum Gal-1, Gal-3, and Gal-9 levels were found to differ according to ANCA positivity status and the presence of renal manifestations.

Conclusions: These results suggest the potential possibility of serum Gal-9 levels in assessing AAV disease activity.
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May 2021

Detection of intracellular monosodium urate crystals in gout synovial fluid using optical diffraction tomography.

Sci Rep 2021 May 11;11(1):10019. Epub 2021 May 11.

Division of Aging Research, Gwangju Center, Korea Basic Science Institute (KBSI), 49 Dosicheomdansaneop-ro, Nam-gu, Gwangju, 61751, South Korea.

Optical diffraction tomography (ODT) enables imaging of unlabeled intracellular components by measuring the three-dimensional (3D) refractive index (RI). We aimed to detect intracellular monosodium urate (MSU) crystals in synovial leukocytes derived from gout patients using ODT. The 3D RI values of the synthetic MSU crystals, measured by ODT, ranged between 1.383 and 1.440. After adding synthetic MSU crystals to a macrophage, RI tomograms were reconstructed using ODT, and the reconstructed RI tomograms discerned intracellular and extracellular MSU crystals. We observed unlabeled synthetic MSU crystal entry into the cytoplasm of a macrophage through time-lapse imaging. Furthermore, using gout patient-derived synovial leukocytes, we successfully obtained RI tomogram images of intracellular MSU crystals. The 3D RI identification of MSU crystals was verified with birefringence through polarization-sensitive ODT measurements. Together, our results provide evidence that this novel ODT can identify birefringent MSU crystals in synovial leukocytes of patients with gout.
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http://dx.doi.org/10.1038/s41598-021-89337-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113554PMC
May 2021

Male Sex Is a Significant Predictor of All-cause Mortality in Patients with Antineutrophil Cytoplasmic Antibody-associated Vasculitis.

J Korean Med Sci 2021 May 10;36(18):e120. Epub 2021 May 10.

Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.

Background: We investigated and compared the initial clinical features at diagnosis and the poor outcomes during follow-up in Korean patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) based on sex.

Methods: The medical records of 223 immunosuppressive drug-naïve patients with AAV were reviewed. Age, body mass index (BMI), smoking history, AAV subtypes, ANCA positivity, clinical manifestations, Birmingham vasculitis activity score (BVAS), five-factor score (FFS), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) at diagnosis were collected. All-cause mortality, end-stage renal disease (ESRD), cerebrovascular accident (CVA) and cardiovascular disease (CVD) were assessed as the poor outcomes of AAV during follow-up.

Results: The median age was 59.0 years and 74 of 223 AAV patients (33.2%) were men. Among variables at diagnosis, male patients exhibited higher BMI than female. However, there were no differences in other demographic data, AAV subtypes, ANCA positivity, BVAS, FFS, ESR and CRP between the two groups. Male patients received cyclophosphamide more frequently, but there were no significant differences in the frequencies of the poor outcomes of AAV between the two groups. Male patients exhibited a significantly lower cumulative patients' survival rate than female patients during the follow-up period based on all-cause mortality ( = 0.037). In the multivariable analysis, both male sex (hazard ratio [HR], 2.378) and FFS (HR, 1.693) at diagnosis were significantly and independently associated with all-cause mortality during follow-up.

Conclusion: Male sex is a significant and independent predictor of all-cause mortality in AAV patients.
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http://dx.doi.org/10.3346/jkms.2021.36.e120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8111045PMC
May 2021

Association Between Serum Alarmin Levels and Disease-specific Indices in Patients With Anti-neutrophil Cytoplasmic Antibody-associated Vasculitis.

In Vivo 2021 May-Jun;35(3):1761-1768

Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea;

Background/aim: We evaluated the relationship between serum alarmin levels and disease-specific indices in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).

Patients And Methods: Sera and data from 79 patients were utilized. For AAV-specific indices, Birmingham vasculitis activity score (BVAS), five-factor score (FFS), and vasculitis damage index (VDI) were collected and serum levels of four alarmins (hepatoma-derived growth factor, high mobility group box protein 1, S100A9, and S100A12) were measured using enzyme-linked immunosorbent assay. Associations between alarmin levels, AAV-specific indices, and inflammatory laboratory markers were assessed.

Results: S100A9 levels were significantly correlated with C-reactive protein levels (r=0.316, p=0.005) and S100A12 levels correlated with VDI (r=0.232, p=0.040), which was consistent in a subgroup of patients with myeloperoxidase (perinuclear)-ANCA positivity. No other associations were found between alarmin levels and BVAS, FFS, and VDI.

Conclusion: The serum S100A12 level was associated with organ damage in AAV, especially in myeloperoxidase (perinuclear)-ANCA-positive patients.
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http://dx.doi.org/10.21873/invivo.12435DOI Listing
June 2021

The novel fibrosis index at diagnosis may predict all-cause mortality in patients with antineutrophil cytoplasmic antibody-associated vasculitis without substantial liver diseases.

Clinics (Sao Paulo) 2021 9;76:e2501. Epub 2021 Apr 9.

Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.

Objectives: Antineutrophil cyto plasmic antibody-associated vasculitis (AAV) is a fatal disease. Currently, predictors of mortality due to AAV are based on the distribution of organ involvement. The novel fibrosis index (NFI) is an index composed of laboratory results that reflect the degree of liver fibrosis. This study aimed to evaluate whether NFI can predict poor outcomes in patients with AAV without substantial liver disease.

Methods: A total of 210 patients with immunosuppressive drug-naïve AAV were retrospectively reviewed. NFI was calculated as follows: NFI=(serum bilirubin × (alkaline phosphatase)2)/(platelet count×(serum albumin)2). NFI cut-off was set at 1.24 (the highest quartile). Poor outcomes were defined as all-cause mortality, relapse, and end-stage renal disease (ESRD).

Results: During the median 34.5 months of follow-up, 21 patients (10%) died, 72 patients (34.3%) relapsed, and 38 patients (18.1%) had ESRD due to AAV progression. The median calculated NFI was 0.61, and it was higher in AAV patients with all-cause mortality than in those without mortality, but the difference was not statistically significant (1.26 vs. 0.59). AAV patients with NFI at diagnosis ≥1.24 exhibited a significantly lower cumulative patient survival rate than those with NFI at diagnosis <1.24 (p=0.002). Multivariate Cox hazard model analysis showed that NFI at diagnosis ≥1.24 was an independent predictor of all-cause mortality in AAV (hazard ratios [HR] 2.850, 95% confidence interval [CI] 1.026, 7.910).

Conclusions: NFI ≥1.24, which may be an independent predictive marker for all-cause mortality in AAV patients without substantial liver disease.
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http://dx.doi.org/10.6061/clinics/2021/e2501DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8009064PMC
April 2021

Correlation between serum cysteine-rich protein 61 and disease activity of antineutrophil cytoplasmic antibody-associated vasculitis.

Clin Rheumatol 2021 Mar 23. Epub 2021 Mar 23.

Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Seoul, Republic of Korea.

Objectives: Cysteine-rich protein 61 (CYR61) stimulates protein kinase B (Akt)-mediated nuclear factor-kappa B (NF-κB) signalling leading to an increase in pro-inflammatory cytokines, which play important roles in the pathogenesis of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Hence, we investigated whether serum CYR61 was correlated with disease activity of AAV in a single-centre prospective cohort.

Methods: Seventy-two patients with AAV were randomly selected and included. Serum CYR61, interleukin (IL)-6 and IL-8 levels were quantified with the patients' stored sera, and clinical and laboratory data at the time of blood sampling were collected. Spearman's correlation and linear regression analysis was conducted to analyse the correlation between continuous variables. The optimal cut-off of serum CYR61 for predicting high disease activity was identified using the receiver operator characteristic curve. Birmingham vasculitis activity score (BVAS) was used as a measure to assess disease activity, and high disease activity was defined as BVAS ≥ 12.

Results: Serum CYR61 significantly correlated with BVAS (r = 0.249), erythrocyte sedimentation rate (r = 0.283), C-reactive protein (r = 0.298) and serum IL-6 (r = 0.319). However, a linear association was not found between CYR61 and BVAS (β = 0.102, P = 0.304). The relative risk (RR) for high disease activity in AAV patients with serum CYR61 ≥ 236.2 pg/mL was higher than those with serum CYR61 < 236.2 pg/mL (RR 3.316, P = 0.018).

Conclusion: Even though serum CYR61 was not directly proportional to the increase of BVAS, it could be predictive of high disease activity in AAV. Key Points • Serum CYR61 was significantly correlated with BVAS along with ESR, CRP and serum IL-6. • The cut-off of serum CYR61 for high disease activity of AAV was obtained as 236.2 pg/mL. • AAV patients with serum CYR61 ≥ 236.2 pg/mL had increased risk of having higher disease activity than those with serum CYR61 < 236.2 pg/mL (RR 3.316, P = 0.018).
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http://dx.doi.org/10.1007/s10067-021-05701-yDOI Listing
March 2021

D-dimer predicts poor hospitalisation outcomes in patients with antineutrophil cytoplasmic autoantibody-associated vasculitis.

Clin Exp Rheumatol 2021 Mar-Apr;39 Suppl 129(2):94-100. Epub 2021 Feb 25.

Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, and Severance Institute for Vascular and Metabolic Research, Yonsei University College of Medicine, Seoul, South Korea.

Objectives: The in-hospital mortality rate among patients with antineutrophil cytoplasmic autoantibody-associated vasculitis (AAV) is high. Unfortunately, there is no reliable prognostic biomarker. This study aimed to investigate whether elevated D-dimer levels can predict hospitalisation outcomes among patients with AAV.

Methods: We performed a retrospective analysis at a tertiary medical centre in Seoul, South Korea, between 2005 and 2019. Patients with AAV requiring hospitalisation, whose D-dimer levels were available within one week of hospitalisation, were included; patients with known alternative reasons for elevated D-dimer were excluded. Death and intensive care unit requirements were defined as adverse outcomes.

Results: In total, 61 AAV patients with a total of 100 episodes of hospitalisation were included. Median D-dimer levels were significantly higher in patients with adverse outcomes than in those without adverse outcomes (1.84 vs. 0.42 mg/dL; p=0.006). Consistently, the incidence of the adverse outcomes was significantly higher in the high D-dimer group (≥0.699 mg/dL; n = 40) than in the low D-dimer group (<0.699 mg/dL; n = 60) (35% vs. 10%; p=0.002). Multivariate logistic regression analysis revealed that a high D-dimer level was a significant risk factor for adverse outcomes (hazard ratio, 4.852; 95% confidence interval, 1.320-17.833; p=0.017). Kaplan-Meier survival analysis revealed that the high D-dimer group was associated with more 30-day in-hospital adverse outcomes than the low D-dimer group (p=0.008).

Conclusions: High D-dimer levels on admission are significantly associated with adverse outcomes among patients with AAV.
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May 2021

Fibrosis-5 predicts end-stage renal disease in patients with microscopic polyangiitis and granulomatosis with polyangiitis without substantial liver diseases.

Clin Exp Med 2021 Feb 20. Epub 2021 Feb 20.

Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, Republic of Korea.

We previously reported that fibrosis-4 (FIB-4) was associated with poor outcomes of microscopic polyangiitis (MPA) and granuloma with polyangiitis (GPA). We also investigated the potential of FIB-5, a novel index, in predicting all-cause mortality and end-stage renal disease (ESRD) during follow-up in patients with MPA and GPA without substantial liver diseases. Clinical and laboratory data at diagnosis were collected by reviewing the medical records of 180 patients with MPA and GPA. FIB-5 was obtained by a following equation: FIB-5 = (serum albumin (g/L) × 0.3 + platelet count (10/L) × 0.05) - (alkaline phosphatase (IU/L) × 0.014 + aspartate aminotransferase/alanine aminotransferase ratio × 6 + 14). The median age of the patients at diagnosis was 61.0 years. FIB-5 at diagnosis could not reflect the cross-sectional vasculitis activity. The cutoffs of FIB-5 for poor outcomes was set as 0.82 (the lowest tertile) and -0.42 (the lowest quartile) at diagnosis. In Kaplan-Meier survival analysis, patients with FIB-5 < 0.82 and those with FIB-5 < -0.42 exhibited lower ESRD-free survival rates than those without. However, it could not predict all-cause mortality. In multivariable Cox hazards analysis, both FFS (Hazard ratio (HR) 1.554) and FIB-5 < 0.82 (HR 2.096) as well as both FFS (HR 1.534) and FIB-5 < -0.42 (HR 2.073) at diagnosis independently predicted ESRD during follow-up. In conclusion, FIB-5 < 0.82 and FIB-5 < -0.42 at diagnosis could predict the occurrence of ESRD, but not all-cause mortality, during follow-up in patients with MPA and GPA without substantial liver diseases.
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http://dx.doi.org/10.1007/s10238-021-00691-2DOI Listing
February 2021

Fibrinogen to albumin ratio reflects the activity of antineutrophil cytoplasmic antibody-associated vasculitis.

J Clin Lab Anal 2021 Apr 16;35(4):e23731. Epub 2021 Feb 16.

Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.

Background: We investigated whether fibrinogen to albumin ratio (FAR) at diagnosis could reflect the cross-sectional activity and predict poor outcomes in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).

Methods: This cross-sectional study included 54 immunosuppressant drug-naïve patients with AAV who had the results of plasma fibrinogen and serum albumin at diagnosis. Clinical and laboratory data at diagnosis were collected, and all-cause mortality, cerebrovascular accident, cardiovascular disease, end-stage renal disease occurrences were assessed as poor outcomes. FAR was calculated by the following equation: FAR = plasma fibrinogen (g/dl)/serum albumin (g/dl).

Results: The median age was 65.5 years, and 59.3% of patients were men (33 MPA, 13 GPA and 8 EGPA). FAR was significantly correlated with Birmingham vasculitis activity score (BVAS; r = 0.271), erythrocyte sedimentation rate (ESR; r = 0.668) and C-reactive protein (CRP; r = 0.638). High BVAS was defined as BVAS ≥16, and the cut-off of FAR at diagnosis was set as 0.118. AAV patients with FAR at diagnosis ≥0.118 had a significantly higher risk for the cross-sectional high BVAS than those without (RR 3.361). In the univariable linear regression analysis, CRP (β = 0.383) and FAR (β = 0.297) were significantly correlated with BVAS at diagnosis. However, in the multivariable analysis, none of them was correlated with the cross-sectional BVAS. FAR at diagnosis could not predict poor outcomes during follow-up in AAV patients.

Conclusions: Fibrinogen to albumin ratio at diagnosis could reflect the cross-sectional BVAS but could not predict poor outcomes in patients with AAV.
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http://dx.doi.org/10.1002/jcla.23731DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8059749PMC
April 2021

Antineutrophil Cytoplasmic Antibody Positivity Is Associated with Vascular Involvement in Behçet's Disease.

Yonsei Med J 2021 Feb;62(2):149-158

Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.

Purpose: We investigated whether antineutrophil cytoplasmic antibody (ANCA) positivity is associated with vascular manifestations at diagnosis of Behçet's disease (BD) and poor outcomes during follow-up.

Materials And Methods: We retrospectively reviewed the medical records of 1060 patients with BD. Among them, 808 patients could be diagnosed with BD based on the revised version of the International Criteria for Behçet's Disease (ICBD) in 2014 (2014 ICBD criteria) and 588 patients could be diagnosed with BD based on the International Study Group (ISG) criteria proposed in 1990 (1990 ISG criteria). We examined the sites and patterns of vascular involvement in the BD patients at diagnosis and evaluated adverse outcomes during follow up, such as all-cause mortality, acute coronary syndrome, and deep vein thrombosis.

Results: Among the 808 patients with BD based on the 2014 ICBD criteria, the rate of ANCA positivity at diagnosis was 2.2%. ANCA-positive BD patients exhibited a higher frequency of overall vascular manifestations (22.2% vs. 6.1%) and higher frequencies of vascular involvement in the upper extremities and visceral arteries than ANCA-negative BD patients (5.6% vs. 0.1% and 5.6% vs. 0.1%). Among the 588 BD patients based on the 1990 ISG criteria, similarly, ANCA-positive BD patients exhibited a higher frequency of vascular manifestations than ANCA-negative BD patients. ANCA positivity, however, did not seem to be associated with poor outcomes in BD patients during follow up.

Conclusion: ANCA positivity in BD patients was found to be associated with cross-sectional vascular involvement in the upper extremities and visceral arteries at diagnosis but was not predictive of poor outcomes during follow-up.
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http://dx.doi.org/10.3349/ymj.2021.62.2.149DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859684PMC
February 2021

Serum Amyloid A Is a Biomarker of Disease Activity and Health-Related Quality-of-Life in Patients with Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

Dis Markers 2020 16;2020:8847306. Epub 2020 Dec 16.

Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.

Serum amyloid A (SAA) is one of the acute phase proteins synthesized in hepatocytes and secreted by various inflammation or infectious stimuli. We investigated the clinical implication of measuring SAA in patients with antineutrophil cytoplasmic antibody- (ANCA-) associated vasculitis (AAV). Seventy-five patients who had been classified as AAV and enrolled in our prospective observational cohort for AAV patients were included. Clinical and laboratory data were obtained on the day of blood sampling, and SAA was measured by ELISA kits. Birmingham Vasculitis Activity Score (BVAS) and Short-Form 36-Item Health Survey (SF-36) were assessed for disease activity and health-related quality-of-life (HRQoL) measures. We stratified patients into having high BVAS when the BVAS was over the median values, and those with either low SF-36 PCS or low SF-36 MCS were defined as having poor HRQoL. Multivariate logistic regression analysis was conducted to estimate independent predictors of high BVAS. The relative risk (RR) was analyzed using the contingency tables and the chi-squared test. SAA was positively correlated with BVAS ( = 0.642) and FFS ( = 0.367) and was inversely correlated with both the SF-36 physical component summary ( = -0.456) and mental component summary scores ( = -0.394). Furthermore, SAA was significantly correlated with acute phase reactants ESR ( = 0.611) and CRP ( = 0.629). Patients with high BVAS exhibited significantly higher SAA than those with low BVAS (1317.1 ng/mL vs. 423.1 ng/mL). In multivariable logistic regression analysis, serum albumin (odds ratio (OR) 0.132) and SAA > 1173.6 ng/mL (OR 15.132) were independently associated with high BVAS. The risk of having high BVAS and poor HRQoL in patients with SAA > 1173.6 ng/mL was higher than in those with SAA ≤ 1173.6 ng/mL (RR 3.419 and 1.493). Our results suggest that SAA might be a useful biomarker in assessing disease activity and HRQoL in AAV.
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http://dx.doi.org/10.1155/2020/8847306DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7787824PMC
December 2020

Systemic inflammation response index predicts all-cause mortality in patients with antineutrophil cytoplasmic antibody-associated vasculitis.

Int Urol Nephrol 2021 Jan 11. Epub 2021 Jan 11.

Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.

Objectives: A systemic inflammation response index (SIRI) has been recently introduced as a tool for the assessment of the prognosis of several critical medical conditions. In this study, we investigated whether SIRI at diagnosis could estimate the cross-sectional disease activity and predict poor prognosis during follow-up in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).

Methods: We reviewed the medical records of 224 immunosuppressive drug-naïve AAV patients and obtained clinical and laboratory data both at diagnosis and during follow-up. SIRI was calculated using the following equation: SIRI = peripheral blood neutrophil count × monocyte count/lymphocyte count.

Results: The median age of AAV patients at diagnosis was 59.0 years and 33% were male. In the univariable linear regression analysis, SIRI value at diagnosis was not significantly correlated with the cross-sectional Birmingham vasculitis activity score (BVAS) (r = 0.125, P = 0.062). When the SIRI cut-off value at diagnosis was set at 2847.9 mm using the receiver operator characteristic curve, the sensitivity was 56.0% and the specificity was 68.3% for all-cause mortality [area 0.618, 95% confidence interval (CI) 0.502, 0.734]. AAV patients with SIRI ≥ 2847.9 mm had a significantly higher risk for all-cause mortality than those with SIRI < 2847.9 mm [relative risk (RR) 2.747, 95% CI 1.181, 6.392]. During follow-up, AAV patients with SIRI ≥ 2847.9 mm exhibited a significantly lower patients' survival rate than those with SIRI < 2847.9 mm (P = 0.003).

Conclusions: SIRI at diagnosis could predict all-cause mortality during follow-up but it could not estimate the cross-sectional BVAS in AAV patients.
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http://dx.doi.org/10.1007/s11255-020-02777-4DOI Listing
January 2021

The significance of cytoplasmic antinuclear antibody patterns in autoimmune liver disease.

PLoS One 2021 7;16(1):e0244950. Epub 2021 Jan 7.

Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea.

We aimed to determine the significance of cytoplasmic antinuclear antibody (ANA) patterns using computer-aided immunofluorescence microscopy in patients with autoimmune liver diseases (AILD). ANA staining pattern was identified by treating cultured human epithelial type 2 (HEp-2) cells with the sera of the patients. Medical records of patients with suspected AILD who had positive cytoplasmic ANA patterns between February 2017 and November 2019 were retrospectively reviewed for clinical, laboratory, and immunological data. Cytoplasmic ANA patterns of AILD and non-AILD groups were compared. Further subgroup analysis of patients with AILD who had reticular or speckled cytoplasmic ANA patterns was conducted. We found that among the 196 patients with positive cytoplasmic ANA patterns, 113 (57.6%) were diagnosed with AILD. The percentage of reticular cytoplasmic pattern was higher in the AILD group than that in the non-AILD group (64.0% vs. 21.9%, p < 0.001). Furthermore, patients with AILD who exhibited a reticular ANA pattern demonstrated a higher positive rate for anti-mitochondrial antibodies (66.7% vs. 2.6%, p < 0.001) than those who exhibited the speckled ANA pattern. Moreover, AILD patients with the reticular ANA pattern displayed a lower positive rate for anti-smooth muscle antibodies (0% vs. 45%, p < 0.001) and nuclear ANA pattern (73.2% vs. 97.5%, p = 0.003) than those with the speckled ANA pattern. Therefore, cytoplasmic ANA patterns could be used to guide AILD characterization in suspected AILD cases, especially as the reticular ANA pattern is strongly associated with AILD. Thus, it is important to check cytoplasmic ANA patterns for AILD evaluation, even when nuclear ANA patterns are negative.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0244950PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790257PMC
May 2021

Drug Survival of Biologic Therapy in Elderly Patients With Rheumatoid Arthritis Compared With Nonelderly Patients: Results From the Korean College of Rheumatology Biologics Registry.

J Clin Rheumatol 2020 Dec 14;Publish Ahead of Print. Epub 2020 Dec 14.

From the Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine Division of Rheumatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, South Korea.

Objective: Although the proportion of elderly patients with rheumatoid arthritis (RA) is increasing, the persistency of biologic therapy in elderly patients requires additional investigation. This study evaluated the drug survival of biologic therapy and associated factors in elderly compared with nonelderly patients.

Methods: This longitudinal observational study included RA patients who were enrolled in the Korean College of Rheumatology Biologics Registry (NCT01965132, started from January 1, 2013) between 2013 and 2015. We compared the retention rate of biologic therapy between elderly (age ≥70 years) and nonelderly (age <70 years) patients, and investigated the causes and predictors of biologic withdrawal in both groups.

Results: Of 682 patients, 122 were aged 70 years or older. The retention rate of biologic therapy at 24 months was 57.8% and 46.5% in nonelderly and elderly patients, respectively (p = 0.027). Biologic withdrawal due to adverse events and inefficacy within 24 months was not significantly different between the 2 groups, although adverse events were more common in elderly patients (20.6% vs 12.8%, p = 0.360). Drug withdrawal due to patient refusal was more common in elderly patients (9.8% vs 1.8%, p < 0.001). In elderly patients, biologic withdrawal was associated with current smoking and older age at disease onset, whereas the use of tumor necrosis factor inhibitors, nonuse of methotrexate, and combination of corticosteroid were important in nonelderly patients.

Conclusions: Elderly RA patients are more likely to discontinue biologic agents within 24 months. To increase the retention rate of biologic therapy, rheumatologists should consider patient characteristics before and during biologic therapy.
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http://dx.doi.org/10.1097/RHU.0000000000001644DOI Listing
December 2020

Efficacy of the fibrosis index for predicting end-stage renal disease in patients with antineutrophil cytoplasmic antibody-associated vasculitis.

Int J Clin Pract 2021 Apr 20;75(4):e13929. Epub 2020 Dec 20.

Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.

Objective: Kidney involvement is a major manifestation of antineutrophil cytoplasmic antibody-associated vasculitis (AAV) and may progress to end-stage renal disease (ESRD), requiring renal replacement therapy. Unfortunately, there is no reliable kidney-specific index for predicting the progression of renal disease to ESRD. The fibrosis index (FI) reflects the degree of fibrosis in chronic liver disease. This study aimed to investigate whether the FI at the time of diagnosis could predict the development of ESRD in AAV patients.

Methods: We retrospectively reviewed the medical records of 211 immunosuppressive drug-naïve AAV patients and extrapolated the cut-off FI value for predicting the development of ESRD using receiver operating characteristic curves. The associations between the FI and clinical outcomes, including mortality, relapse, and ESRD development, were determined.

Results: Overall, 39 (18.5%) patients developed ESRD owing to the progression of AAV-associated renal disease. The median FI was higher in AAV patients with ESRD than in those without (1.61 vs 1.04; P = .001). The FI cut-off was 1.72. The incidence of ESRD was higher in patients with FI ≥ 1.72 at the time of diagnosis than in those with an FI < 1.72 at the time of diagnosis (relative risk: 4.655; 95% confidence interval: 2.242-9.662; P < .001). Kaplan-Meier survival analysis revealed that patients with an FI ≥ 1.72 at the time of diagnosis exhibited significantly lower ESRD-free survival rates than those with an FI < 1.72 at the time of diagnosis (P < .001).

Conclusion: FI ≥ 1.72 at the time of diagnosis may be an independent predictive marker for ESRD in AAV patients.
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http://dx.doi.org/10.1111/ijcp.13929DOI Listing
April 2021

Pan-immune-inflammation value at diagnosis independently predicts all-cause mortality in patients with antineutrophil cytoplasmic antibody-associated vasculitis.

Clin Exp Rheumatol 2021 Mar-Apr;39 Suppl 129(2):88-93. Epub 2020 Nov 10.

Division of Rheumatology, Department of Internal Medicine and Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul, Republic of Korea.

Objectives: The pan-immune-inflammation value (PIIV), a novel, validated predictor of the prognosis of several diseases, has been recently introduced. We investigated whether PIIV at diagnosis could predict all-cause mortality during follow-up in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).

Methods: Medical records of 219 immunosuppressive drug-naïve patients with AAV were reviewed. PIIV was calculated as follows: neutrophil count (x 1000/m3) x monocyte count (x 1000/m3) x platelet count (x 1000/mm3) / lymphocyte count (x 1000/m3). Additionally, conventional risk factors of mortality, AAV-specific indices, and acute-phase reactants at diagnosis were evaluated.

Results: The median age at diagnosis was 59.0 years and 32.9% of the patients were male. During follow-up, 24 patients (11.0%) died due to all causes. When the cut-off of PIIV at diagnosis for all-cause mortality was set at 1011.3, sensitivity and specificity of 52.0% and 71.2%, were attained (p=0.041). When AAV patients were divided into two groups according to the calculated cut-off, those with PIIV ≥1011.3 at diagnosis had a significantly lower cumulative survival rate than those without (p=0.009). In the multivariable Cox hazards model analysis, male gender (HR 2.307), FFS (HR 1.728) and PIIV ≥1011.3 (HR 2.689) were identified as significant and independent risk factors of all-cause mortality.

Conclusions: PIIV at diagnosis exceeding the optimal cut-off for death could predict all-cause mortality during follow-up in AAV patients comparable to male gender and FFS at diagnosis.
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May 2021

Serum granzyme B is associated with otorhinolaryngological, pulmonary, and renal involvement of antineutrophil cytoplasmic antibody-associated vasculitis.

J Investig Med 2021 01 12;69(1):91-95. Epub 2020 Nov 12.

Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea (the Republic of)

We investigated whether serum granzyme B (GrB) can reflect the inflammatory burden such as cross-sectional disease activity and organ-specific involvement in immunosuppressive drug-naïve patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Seventy-eight immunosuppressive drug-naïve patients with AAV were included in this study. At the time of the first classification, whole blood was obtained from each patient and sera was immediately isolated and stored at - 80℃. On the day of the blood sampling, we performed routine laboratory tests including antineutrophil cytoplasmic antibody tests and collected both clinical and laboratory data. AAV-specific indices included Birmingham Vasculitis Activity Score (BVAS) and Five-Factor Score (FFS). The median age of patients with AAV was 62 years and 26 patients were men. Serum GrB was not associated with the cross-sectional BVAS; however, patients with serum GrB positivity exhibited higher frequencies of otorhinolaryngological manifestation than those without (p=0.037). When serum GrB levels were compared after dividing the patients into two groups based on the presence of organ-specific involvement, patients with pulmonary involvement exhibited a significantly higher serum GrB than those without (p=0.042). On the other hand, patients with renal involvement showed a significantly lower serum GrB than those without (p=0.023). In addition, serum GrB was inversely correlated with the cross-sectional FFS (r=-0.249, p=0.028). Even though serum GrB could not reflect the inflammatory burden of AAV, serum GrB was associated with otorhinolaryngological, pulmonary, and renal involvement in immunosuppressive drug-naïve patients with AAV.
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http://dx.doi.org/10.1136/jim-2020-001365DOI Listing
January 2021

Pregnancy Morbidities in Korean Patients with Takayasu Arteritis: A Monocentric Pilot Study.

Yonsei Med J 2020 Nov;61(11):970-975

Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.

We investigated pregnancy morbidities in Korean patients with Takayasu arteritis (TA) in a single tertiary hospital as a pilot study. We retrospectively reviewed the medical records of 12 pregnancies in seven patients with TA. All patients were diagnosed with TA based on the 1990 American College of Rheumatology classification criteria. The medical records of patients were well-documented, allowing review of clinical data including pregnancy morbidities. The angiographic and Ishikawa classifications at diagnosis and TA activity at delivery were assessed. Of the 12 pregnancies, two pregnancies ended in spontaneous abortion (16.7%), and one pregnancy (8.3%) had therapeutic abortion at 9 weeks due to maternal morbidity. Among the remaining nine pregnancies, only one child was delivered via normal spontaneous vaginal delivery, and the remaining eight were delivered by Caesarean section. Two out of nine (22.2%) neonates were born with low birth weight, and one of them was born at 30 weeks of gestation. The most common maternal complication was hypertension affecting 7/12 (58.3%) pregnancies. Preeclampsia occurred in one pregnancy, and gestational diabetes mellitus (GDM) occurred in two pregnancies. At delivery, disease activity of TA was stable in all pregnancies, and glucocorticoids were administered in nine pregnancies. Live birth rate of pregnant Korean patients with TA was 75%. Future studies are needed to reduce pregnancy-related complications.
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http://dx.doi.org/10.3349/ymj.2020.61.11.970DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7593103PMC
November 2020

Worse Renal Presentation and Prognosis in Initial-Onset Lupus Nephritis than Early-Onset Lupus Nephritis.

Yonsei Med J 2020 Nov;61(11):951-957

Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.

Purpose: To compare the clinical characteristics and renal outcomes between patients who initially had lupus nephritis (LN) at the onset of systemic lupus erythematosus (SLE) (initial-onset LN) and those who developed LN within 5 years after SLE onset (early-onset LN).

Materials And Methods: SLE patients with biopsy-proven LN were retrospectively reviewed. The clinical parameters and renal outcomes were compared between initial-onset and early-onset LN groups. We used Cox regression analysis to estimate risk of worse renal outcomes according to the onset time of LN.

Results: Of all 136 LN patients, 92 (67.6%) and 44 (32.4%) patients were classified into the initial-onset and early-onset LN groups, respectively. The initial-onset LN group had higher prevalences of class IV LN (54.3% vs. 34.1%, =0.027), impaired renal function (34.8% vs. 11.4%, =0.004), microscopic hematuria (73.9% vs. 54.5%, =0.024), and higher urine protein/creatinine ratio [4626.1 (2180.0-6788.3) mg/g vs. 2410.0 (1265.0-5168.5) mg/g, =0.006] at LN diagnosis. Renal relapse (46.3% vs. 25.7%, =0.039) and progression to chronic kidney disease (CKD) or end-stage renal disease (ESRD) were more common (24.4% vs. 8.3%, =0.042) in the initial-onset LN group. In Cox regression analysis, the initial-onset LN group had higher risks of renal relapse [adjusted hazard ratio (HR) 3.56, 95% confidence interval (CI) 1.51-8.35, =0.004] and progression to CKD or ESRD (adjusted HR 4.57, 95% CI 1.03-20.17, =0.045), compared with the early-onset LN group.

Conclusion: Patients with LN at SLE onset may have more severe renal presentations and experience worse renal outcomes than those who develop LN within 5 years.
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http://dx.doi.org/10.3349/ymj.2020.61.11.951DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7593100PMC
November 2020

Clinical and imaging findings suggestive of histopathological immunoglobulin G4-related disease: a single-center retrospective study.

Clin Rheumatol 2021 Apr 28;40(4):1423-1430. Epub 2020 Aug 28.

Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, Republic of Korea.

Objective: To investigate the clinical and imaging features predicting the histopathological diagnosis of immunoglobulin G4 (IgG4)-related disease (IgG4RD) in patients with suspected IgG4RD on computed tomography (CT).

Methods: We retrospectively reviewed the medical records of 178 patients with CT findings suspicious of IgG4RD from January 2015 to December 2017. Patients who underwent tissue biopsy were included to evaluate the association between patient characteristics and histopathological diagnosis of IgG4RD. The histopathological diagnosis was classified into IgG4RD and non-IgG4RD. Clinical, laboratory, and imaging features were compared between patients with IgG4RD and non-IgG4RD, and logistic regression analysis was performed to identify the predictors for histopathologically confirmed IgG4RD.

Results: Of the 103 patients with histopathologically proven diseases, 46 and 57 patients were classified as IgG4RD and non-IgG4RD, respectively. The median age was 64 years; 65% of patients were male. There were significant differences in sex (P = 0.035), fever (P = 0.039), serum IgG4 level (P < 0.001), renal involvement (P = 0.036), lacrimal or salivary glands involvement (P = 0.050), swelling pattern on CT (P = 0.001), and positron emission tomography (PET)-CT findings (P < 0.001) between patients with IgG4RD and non-IgG4RD. Multivariate analysis revealed elevated IgG4 level > 135 mg/dL (odds ratio [OR] = 5.418, P < 0.001), kidney involvement (OR = 6.170, P = 0.044), and the swelling feature on CT (OR = 4.301, P = 0.012) to be independent factors for histopathological diagnosis of IgG4RD.

Conclusion: This study suggests that elevated IgG4 level, renal involvement, and swelling pattern on CT are associated with histopathological diagnosis of IgG4RD. The clinical and imaging features might help to decide further evaluation in patients with clinically suspected IgG4RD. Key Points • Computed tomography (CT) is not sufficient to discriminate between IgG4-related disease (IgG4RD) and non-IgG4RD conditions. • Histopathological diagnosis of IgG4RD is associated with elevated IgG4 level, renal involvement, and swelling pattern on CT. • Positron emission tomography-CT may be a useful diagnostic tool in patients with clinically suspected IgG4RD. >.
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http://dx.doi.org/10.1007/s10067-020-05366-zDOI Listing
April 2021

Clinical features of Korean elderly patients with antineutrophil cytoplasmic antibody-associated vasculitis.

Korean J Intern Med 2021 May 20;36(3):731-741. Epub 2020 Aug 20.

Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.

Background/aims: We compared the clinical and laboratory data between elderly and non-elderly patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) at diagnosis; further, we investigated the predictors at diagnosis for all-cause mortality and end-stage renal disease (ESRD) occurrence during follow-up in Korean elderly patients with AAV.

Methods: We reviewed the medical records of 191 AAV patients regarding clinical manifestations and laboratory results at diagnosis and during follow-up. The follow-up duration was defined as the period from diagnosis to death for deceased patients or to the time of dialysis for ESRD patients, or to the last visit. Elderly (n = 67) and non-elderly (n = 124) patients were grouped based on an age threshold of 65 years.

Results: At diagnosis, elderly patients exhibited higher median Birmingham Vasculitis Activity Score (BVAS) and higher frequencies of ANCA positivity and pulmonary manifestations than non-elderly patients. Furthermore, elderly patients exhibited increased median white blood cell count, blood urea nitrogen (BUN), alkaline phosphatase, erythrocyte sedimentation rate, and C-reactive protein and decreased median hemoglobin. However, there were no significant differences in all-cause mortality and ESRD occurrence between elderly and non-elderly patients. Meanwhile, elderly patients exhibited lower cumulative patients' and ESRD-free survival rates than non-elderly patients. In the multivariable Cox hazards model, BUN, creatinine and serum albumin at diagnosis were independent predictors for ESRD occurrence, whereas there were no independent predictors at diagnosis for all-cause mortality.

Conclusion: Elderly AAV patients exhibited substantially higher rates of all-cause mortality and ESRD occurrence during follow-up compared than non-elderly AAV patients.
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http://dx.doi.org/10.3904/kjim.2020.039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8137396PMC
May 2021

Evaluation of body composition using computed tomography in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis.

Korean J Intern Med 2020 Aug 18. Epub 2020 Aug 18.

Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.

Background/aims: Measures of body composition, including visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and skeletal muscle area (SMA), are considered important prognostic factors in chronic diseases. The association of these measures with auto-inflammatory disorders, such as anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV), remains unclear. We investigated the clinical significance of VAT, SAT, and SMA in patients with AAV.

Methods: Patients with AAV subjected to chest computed tomography (CT), abdominal CT, or positron emission tomography-CT on diagnosis of AAV were evaluated. Quantitative assessment of VAT, SAT, and SMA was performed at the third lumbar vertebral level and computed by summing the pixel attenuation for tissue-specific Hounsfield units in the corresponding region. Associations of VAT, SAT, and SMA with clinical and laboratory data and clinical outcome measures were evaluated.

Results: Of the 117 patients, 61 (52.1%) were classified as having microscopic polyangiitis, 28 (23.9%) as granulomatosis with polyangiitis, and 28 (23.9%) as eosinophilic granulomatosis with polyangiitis. VAT significantly correlated with age, weight, body mass index (BMI), and Birmingham Vasculitis Activity Score, whereas SAT correlated with weight, BMI, and creatinine levels. A significant association was found between SMA and age, height, weight, BMI, and the Five-Factor Score. Cox proportional hazards analysis showed that creatinine levels (odds ratio [OR], 1.346; 95% confidence interval [CI], 1.034 to 1.753; p = 0.027) and high VAT (OR, 7.137; 95% CI, 1.343-37.946; p = 0.021) were independently associated with all-cause mortality during follow-up.

Conclusions: Evaluation of VAT using CT is useful for estimating disease activity and all-cause mortality in patients with AAV.
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http://dx.doi.org/10.3904/kjim.2020.064DOI Listing
August 2020

Atherogenic index of plasma predicts cerebrovascular accident occurrence in antineutrophil cytoplasmic antibody-associated vasculitis.

Lipids Health Dis 2020 Aug 14;19(1):184. Epub 2020 Aug 14.

Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, Republic of Korea, 03722.

Background: To investigate whether atherogenic index of plasma (AIP) at diagnosis is associated with the occurrence of cerebrovascular accident (CVA) or coronary artery disease (CAD) in antineutrophil cytoplasmic antibody-associated vasculitis (AAV).

Methods: The medical records of 167 AAV patients on initial diagnosis was reviewed, and 300 healthy controls were included. AIP was calculated using the following equation: AIP = Log (triglyceride [mg/dL] / high-density lipoprotein cholesterol [mg/dL]). AAV patients were divided into two groups according to the AIP cut-off of 0.11. The event of stroke, transient ischemic attack, and cerebral hemorrhage was recorded as CVA, and CAD events consisted of either myocardial infarction and angina pectoris. CVA- and CAD- free survival rate between those with AIP ≥ 0.11 and < 0.11 were compared by the Kaplan-Meier analysis, and Cox hazard analysis was conducted to identify predictors of CVA.

Results: The median age of AAV patients were 59.0 years, and 54 (32.3%) patients were male. One-hundred and fifteen (68.9%) patients had AIP < 0.11 and 52 (31.1%) had AIP ≥ 0.11. The mean Birmingham vasculitis activity score in AAV patients with AIP < 0.11 was lower than that seen in patients with AIP ≥ 0.11 (12.0 vs. 14.0, P = 0.041). AAV patients had a significantly higher AIP compared to controls (mean - 0.01 vs. -0.10, P < 0.001). During follow-up, the occurrence of CVA and CAD was observed in 16 (9.6%) and 14 (8.4%) patients, respectively. In Kaplan-Meier analysis, AAV patients with AIP ≥ 0.11 had significantly lower CVA-free survival rates than in those with AIP < 0.11 (P = 0.027), whereas there was no difference in CAD according to AIP (P = 0.390). Multivariable Cox analysis indicated that AIP ≥ 0.11 at diagnosis was the sole predictor of CVA (Hazard ratio 3.392, 95% confidence interval 1.076, 10.696, P = 0.037).

Conclusions: AIP is significantly higher in AAV patients than in healthy controls, and AIP ≥ 0.11 at diagnosis is a significant predictor of CVA during follow-up. Stringent surveillance should be provided in AAV patients with AIP ≥ 0.11 regarding the occurrence of CVA.

Trial Registration: Retrospectively registered (4-2017-0673).
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http://dx.doi.org/10.1186/s12944-020-01360-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7429760PMC
August 2020

Soluble Lectin-Like Oxidized Low-Density Lipoprotein Receptor 1 Is Inversely Correlated with the Activity of ANCA-Associated Vasculitis.

Yonsei Med J 2020 Aug;61(8):720-725

Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.

Lectin-like oxidized low-density lipoprotein (LDL) receptor 1 (LOX1) binds to oxidized LDL, which is associated with inflammation in various vascular disorders. Here, we aimed to investigate the potential of soluble LOX1 (sLOX1) as an indicator of antineutrophil cytoplasmic antibody-associated vasculitis (AAV) activity. Serum levels of sLOX1 in frozen samples from patients with AAV enrolled in a prospective observational cohort study at the Severance Hospital were measured using enzyme-linked immunosorbent assay. Clinical and laboratory data were collected on the date when the blood sampling was performed. The association between sLOX1 and clinical and laboratory data was assessed using Pearson's correlation analysis. The median age of the recruited 79 patients was 62.0 years, and 27 (34.2%) patients were men. The median Birmingham vasculitis activity score (BVAS), five-factor score, vasculitis damage index, and sLOX1 level were 6, 1, 3, and 911.9 pg/mL, respectively. Correlation analysis based on BVAS revealed that sLOX1 and total cholesterol were significantly inversely correlated with BVAS (r=-0.224, =0.047 and r=-0.424, <0.001, respectively). No significant correlations were observed between continuous variables and sLOX1 except for BVAS, although total cholesterol tended to correlate with sLOX1 (r=0.190, =0.093). Additionally, sLOX1 was not influenced by sex, hypertension, diabetes mellitus, or the presence of pulmonary, cardiovascular, and renal involvement of AAV. In summary, sLOX1 was inversely correlated with BVAS in AAV patients, which is different from other vascular diseases or inflammatory diseases.
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http://dx.doi.org/10.3349/ymj.2020.61.8.720DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7393288PMC
August 2020

Rituximab Biosimilar Prevents Poor Outcomes of Microscopic Polyangiitis and Granulomatosis with Polyangiitis as Effectively as Rituximab Originator.

Yonsei Med J 2020 Aug;61(8):712-719

Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.

Purpose: There has been no extensive study to compare the efficacy between rituximab originator (Mabthera®) and its biosimilar (Truxima®) for microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). Here, we investigated the clinical effects of rituximab on poor outcomes of MPA and GPA in Korean patients, and compared those between Mabthera® and Truxima®.

Materials And Methods: We retrospectively reviewed the medical records of a total of 139 patients, including 97 MPA patients and 42 GPA patients. At diagnosis, antineutrophil cytoplasmic antibody positivity and comorbidities were assessed. During follow-up, all-cause mortality, relapse, end-stage renal disease, cerebrovascular accident and acute coronary syndrome were evaluated as poor outcomes. In this study, rituximab was used as either Mabthera® or Truxima®.

Results: The median age at diagnosis was 60.1 years and 46 patients were men (97 MPA and 42 GPA patients). Among poor outcomes, patients receiving rituximab exhibited a significantly lower cumulative relapse-free survival rate compared to those not receiving rituximab (=0.002). Nevertheless, rituximab use did not make any difference in other poor outcomes of MPA and GPA except for relapse, which might be a rebuttal to the fact that rituximab use after relapse eventually led to better prognosis. There were no significant differences in variables at diagnosis and during follow-up between patients receiving Mabthera® and those receiving Truxima®. Patients receiving Truxima® exhibited a similar pattern of the cumulative survival rates of each poor outcome to those receiving Mabthera®.

Conclusion: Truxima® prevents poor outcomes of MPA and GPA as effectively as does Mabthera®.
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http://dx.doi.org/10.3349/ymj.2020.61.8.712DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7393299PMC
August 2020

Comparison of clinical features and outcomes between patients with early and delayed lupus nephritis.

BMC Nephrol 2020 07 7;21(1):258. Epub 2020 Jul 7.

Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.

Background: Lupus nephritis is associated with increased risk of end-stage renal disease (ESRD) and all-cause mortality. We evaluated the clinical features and outcomes of patients with early and delayed lupus nephritis.

Methods: The medical records of 171 patients who met the 1997 revised classification criteria for systemic lupus erythematosus (SLE) with pathologic confirmation of lupus nephritis were reviewed. Early lupus nephritis was defined when lupus nephritis was histopathologically confirmed as the first clinical manifestation of SLE, whereas delayed lupus nephritis was defined as lupus nephritis that was identified after the diagnosis of SLE. Clinical and laboratory data, as well as kidney histopathology and medication usage were investigated. Kaplan-Meier and Cox-proportional hazard analysis was performed to compare the outcomes of early and delayed lupus nephritis and evaluate factors associated with ESRD and all-cause mortality.

Results: Patients with early lupus nephritis had higher disease activity (median non-renal SLE disease activity index-2000, 6.0 vs. 4.0; p < 0.001) and more frequent skin rash, oral ulcer and serositis; however, the proportion of patients with higher renal chronicity index was greater in the delayed lupus nephritis group (p = 0.007). Nevertheless, no difference was found regarding ESRD and all-cause mortality between the groups. In Cox-proportional hazard analysis, C-reactive protein level, creatinine level and chronicity index were factors associated with ESRD, while age and haemoglobin level were associated with all-cause mortality.

Conclusions: In conclusion, clinical outcomes of early and delayed lupus nephritis are not significantly different. Rigorous adherence to current treatment recommendations is essential for the treatment of lupus nephritis.
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http://dx.doi.org/10.1186/s12882-020-01915-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7341643PMC
July 2020

Serum Mannose-Binding Lectin Levels Are Correlated with the Disease Activity of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: A Single-Center Study.

Tohoku J Exp Med 2020 06;251(2):117-123

Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine.

Mannose-binding lectin (MBL) is a soluble pattern-recognition molecule, which plays a crucial role in the innate immune system and the activation of lectin complement pathway. Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is an autoimmune disease affecting the small vasculatures and is characterized by the alteration of innate and adaptive immunity and complement activation. In this study, we investigated whether serum MBL is associated with disease activity of AAV, which was measured by ELISA. Associations between serum MBL and AAV-specific indices, as well as clinical and laboratory data were assessed using Kendall's tau. Among the 80 patients, 42 (52.5%), 21 (26.3), and 17 (21.3%) patients were classified as microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA), and eosinophilic granulomatosis with polyangiitis (EGPA), respectively. The median values of erythrocyte sedimentation rate, C-reactive protein, and serum MBL were 36.5 (normal range < 20) mm/h, 2.4 (normal range < 8) mg/dL, and 8.6 ng/mL, respectively. The median serum levels of MBL in MPA, GPA, and EGPA patients were 8.4, 9.3, and 8.2 ng/mL. Correlation analysis showed that serum MBL was associated with Birmingham Vasculitis Activity Score (BVAS) (R = 0.169, p = 0.027), but not with other AAV-specific indices and clinical and laboratory data. In addition, serum MBL was significantly associated with the pulmonary manifestation score based on BVAS (R = 0.247, p = 0.001). In summary, among the AAV-specific indices and clinical and laboratory variables analyzed, serum MBL is correlated with BVAS and pulmonary manifestation score based on the BVAS.
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http://dx.doi.org/10.1620/tjem.251.117DOI Listing
June 2020