Publications by authors named "Diane L Kamen"

136 Publications

Neuropsychiatric Events in Systemic Lupus Erythematosus.

Arthritis Rheumatol 2021 May 27. Epub 2021 May 27.

Copenhagen Lupus and Vasculitis Clinic, 4242, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.

Objectives: To determine predictors for change in neuropsychiatric (NP) event status in a large, prospective, international, inception cohort of SLE patients METHODS: Upon enrollment and annually thereafter, NP events attributed to SLE and non-SLE causes and physician determined resolution were documented. Factors potentially associated with onset and resolution of NP events were determined by time-to-event analysis using a multistate modelling structure.

Results: NP events occurred in 955/1,827 (52.3%) patients and 592/1910 (31.0%) unique events were attributed to SLE. For SLE NP events multivariate analysis revealed positive associations with male sex, concurrent non-SLE NP events excluding headache, active SLE and corticosteroids. There was a negative association with Asian race/ethnicity, post-secondary education, and immunosuppressive or anti-malarial drugs. For non-SLE NP events, excluding headache, there was a positive association with concurrent SLE NP events and negative associations with African and Asian race/ethnicity. NP events attributed to SLE had a higher resolution rate than non-SLE NP events, with the exception of headache that had comparable resolution rates. For SLE NP events, multivariate analysis revealed resolution was more common with Asian race/ethnicity and for central/focal NP events. For non-SLE NP events resolution was more common with African race/ethnicity and less common with older age at SLE diagnosis.

Conclusions: In a large and long-term study of the occurrence and resolution of NP events in SLE we identified subgroups with better and worse prognosis. The course of NP events differs greatly depending on their nature and attribution.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/art.41876DOI Listing
May 2021

Genetic landscape of Gullah African Americans.

Am J Phys Anthropol 2021 Aug 19;175(4):905-919. Epub 2021 May 19.

Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, USA.

Objectives: Gullah African Americans are descendants of formerly enslaved Africans living in the Sea Islands along the coast of the southeastern U.S., from North Carolina to Florida. Their relatively high numbers and geographic isolation were conducive to the development and preservation of a unique culture that retains deep African features. Although historical evidence supports a West-Central African ancestry for the Gullah, linguistic and cultural evidence of a connection to Sierra Leone has led to the suggestion of this country/region as their ancestral home. This study sought to elucidate the genetic structure and ancestry of the Gullah.

Materials And Methods: We leveraged whole-genome genotype data from Gullah, African Americans from Jackson, Mississippi, African populations from Sierra Leone, and population reference panels from Africa and Europe to infer population structure, ancestry proportions, and global estimates of admixture.

Results: Relative to non-Gullah African Americans from the Southeast US, the Gullah exhibited higher mean African ancestry, lower European admixture, a similarly small Native American contribution, and increased male-biased European admixture. A slightly tighter bottleneck in the Gullah 13 generations ago suggests a largely shared demographic history with non-Gullah African Americans. Despite a slightly higher relatedness to populations from Sierra Leone, our data demonstrate that the Gullah are genetically related to many West African populations.

Discussion: This study confirms that subtle differences in African American population structure exist at finer regional levels. Such observations can help to inform medical genetics research in African Americans, and guide the interpretation of genetic data used by African Americans seeking to explore ancestral identities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajpa.24333DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8286328PMC
August 2021

Anti-beta 2 glycoprotein I IgA in the SLICC classification criteria dataset.

Lupus 2021 Jul 6;30(8):1283-1288. Epub 2021 May 6.

Amsterdam University Medical Centres, University of Amsterdam, Amsterdam, Netherlands.

Objective: Anti-beta 2 glycoprotein I IgA is a common isotype of anti-beta 2 glycoprotein I in SLE. Anti-beta 2 glycoprotein I was not included in the American College of Rheumatology (ACR) SLE classification criteria, but was included in the Systemic Lupus International Collaborating Clinics (SLICC) criteria. We aimed to evaluate the prevalence of anti-beta 2-glycoprotein I IgA in SLE versus other rheumatic diseases. In addition, we examined the association between anti-beta 2 glycoprotein I IgA and disease manifestations in SLE.

Methods: The dataset consisted of 1384 patients, 657 with a consensus physician diagnosis of SLE and 727 controls with other rheumatic diseases. Anti-beta 2 glycoprotein I isotypes were measured by ELISA. Patients with a consensus diagnosis of SLE were compared to controls with respect to presence of anti-beta 2 glycoprotein I. Among patients with SLE, we assessed the association between anti-beta 2 glycoprotein I IgA and clinical manifestations.

Results: The prevalence of anti-beta 2 glycoprotein I IgA was 14% in SLE patients and 7% in rheumatic disease controls (odds ratio, OR 2.3, 95% CI: 1.6, 3.3). It was more common in SLE patients who were younger patients and of African descent (p = 0.019). Eleven percent of SLE patients had anti-beta 2 glycoprotein I IgA alone (no anti-beta 2 glycoprotein I IgG or IgM). There was a significant association between anti-beta 2 glycoprotein I IgA and anti-dsDNA (p = 0.001) and the other antiphospholipid antibodies (p = 0.0004). There was no significant correlation of anti-beta 2 glycoprotein I IgA with any of the other ACR or SLICC clinical criteria for SLE. Those with anti-beta 2 glycoprotein I IgA tended to have a history of thrombosis (12% vs 6%, p = 0.071), but the difference was not statistically significant.

Conclusion: We found the anti-beta 2 glycoprotein I IgA isotype to be more common in patients with SLE and in particular, with African descent. It could occur alone without other isotypes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/09612033211014248DOI Listing
July 2021

Development and implementation of a virtual Lupus Patient Education Event during the COVID-19 pandemic.

Lupus Sci Med 2021 03;8(1)

Department of Medicine, Division of Rheumatology and Immunology, Medical University of South Carolina, Charleston, South Carolina, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/lupus-2021-000493DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7948152PMC
March 2021

European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) SLE classification criteria item performance.

Ann Rheum Dis 2021 Feb 10. Epub 2021 Feb 10.

Department of Medicine, Division of Rheumatology, University of California at San Francisco and the VA Medical Center, San Francisco, California, USA.

Background/objectives: The European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) 2019 classification criteria for systemic lupus erythematosus system showed high specificity, while attaining also high sensitivity. We hereby analysed the performance of the individual criteria items and their contribution to the overall performance of the criteria.

Methods: We combined the EULAR/ACR derivation and validation cohorts for a total of 1197 systemic lupus erythematosus (SLE) and n=1074 non-SLE patients with a variety of conditions mimicking SLE, such as other autoimmune diseases, and calculated the sensitivity and specificity for antinuclear antibodies (ANA) and the 23 specific criteria items. We also tested performance omitting the EULAR/ACR criteria attribution rule, which defines that items are only counted if not more likely explained by a cause other than SLE.

Results: Positive ANA, the new entry criterion, was 99.5% sensitive, but only 19.4% specific, against a non-SLE population that included other inflammatory rheumatic, infectious, malignant and metabolic diseases. The specific criteria items were highly variable in sensitivity (from 0.42% for delirium and 1.84% for psychosis to 75.6% for antibodies to double-stranded DNA), but their specificity was uniformly high, with low C3 or C4 (83.0%) and leucopenia <4.000/mm³ (83.8%) at the lowest end. Unexplained fever was 95.3% specific in this cohort. Applying the attribution rule improved specificity, particularly for joint involvement.

Conclusions: Changing the position of the highly sensitive, non-specific ANA to an entry criterion and the attribution rule resulted in a specificity of >80% for all items, explaining the higher overall specificity of the criteria set.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/annrheumdis-2020-219373DOI Listing
February 2021

Lower vitamin D is associated with metabolic syndrome and insulin resistance in systemic lupus: data from an international inception cohort.

Rheumatology (Oxford) 2021 Feb 8. Epub 2021 Feb 8.

Department of Rheumatology, Kantonsspital Schaffhausen, Schaffhausen, Schaffhausen, CH.

Objectives: Vitamin D (25(OH)D) deficiency and metabolic syndrome (MetS) may both contribute to increased cardiovascular risk in systemic lupus erythematosus (SLE). We aimed to examine the association of demographic factors, SLE phenotype, therapy and vitamin D levels with MetS and insulin resistance.

Methods: The Systemic Lupus International Collaborating Clinics (SLICC) enrolled patients recently diagnosed with SLE (<15 months) from 33 centres across 11 countries from 2000. Clinical, laboratory and therapeutic data were collected. Vitamin D level was defined according to tertiles based on distribution across this cohort, which were set at T1 (10-36 nmol/l), T2 (37-60 nmol/l) and T3 (61-174 nmol/l). MetS was defined according to the 2009 consensus statement from the International Diabetes Federation. Insulin resistance was determined using the HOMA-IR model. Linear and logistic regressions were used to assess the association of variables with vitamin D levels.

Results: Of the 1847 patients, 1163 (63%) had vitamin D measured and 398 (34.2%) subjects were in the lowest 25(OH)D tertile. MetS was present in 286 of 860 (33%) patients whose status could be determined. Patients with lower 25(OH)D were more likely to have MetS and higher HOMA-IR. The MetS components, hypertension, hypertriglyceridemia and decreased HDL were all significantly associated with lower 25(OH)D. Increased average glucocorticoid exposure was associated with higher insulin resistance.

Conclusions: MetS and insulin resistance are associated with lower vitamin D in patients with SLE. Further studies could determine whether vitamin D repletion confers better control of these cardiovascular risk factors and improve long-term outcomes in SLE.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/rheumatology/keab090DOI Listing
February 2021

Rigorous Plasma Microbiome Analysis Method Enables Disease Association Discovery in Clinic.

Front Microbiol 2020 8;11:613268. Epub 2021 Jan 8.

Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, United States.

Blood microbiome is important to investigate microbial-host interactions and the effects on systemic immune perturbations. However, this effort has met with major challenges due to low microbial biomass and background artifacts. In the current study, microbial 16S DNA sequencing was applied to analyze plasma microbiome. We have developed a quality-filtering strategy to evaluate and exclude low levels of microbial sequences, potential contaminations, and artifacts from plasma microbial 16S DNA sequencing analyses. Furthermore, we have applied our technique in three cohorts, including tobacco-smokers, HIV-infected individuals, and individuals with systemic lupus erythematosus (SLE), as well as corresponding controls. More than 97% of total sequence data was removed using stringent quality-filtering strategy analyses; those removed amplicon sequence variants (ASVs) were low levels of microbial sequences, contaminations, and artifacts. The specifically enriched pathobiont bacterial ASVs have been identified in plasmas from tobacco-smokers, HIV-infected individuals, and individuals with SLE but not from control subjects. The associations between these ASVs and disease pathogenesis were demonstrated. The pathologic activities of some identified bacteria were further verified . We present a quality-filtering strategy to identify pathogenesis-associated plasma microbiome. Our approach provides a method for studying the diagnosis of subclinical microbial infection as well as for understanding the roles of microbiome-host interaction in disease pathogenesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmicb.2020.613268DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7820181PMC
January 2021

Prediction of hospitalizations in systemic lupus erythematosus using the Systemic Lupus International Collaborating Clinics Frailty Index (SLICC-FI).

Arthritis Care Res (Hoboken) 2020 Nov 5. Epub 2020 Nov 5.

Emory University School of Medicine, Division of Rheumatology, Atlanta, Georgia, USA.

Objective: The Systemic Lupus International Collaborating Clinics (SLICC) frailty index (FI) predicts mortality and damage accrual in SLE, but its association with hospitalizations has not been described. We estimated the association of baseline SLICC-FI values with future hospitalizations in the SLICC inception cohort.

Methods: Baseline SLICC-FI scores were calculated. The number and duration of inpatient hospitalizations during follow-up were recorded. Negative binomial regression was used to estimate the association between baseline SLICC-FI values and the rate of hospitalizations per patient-year of follow-up. Linear regression was used to estimate the association of baseline SLICC-FI scores with the proportion of follow-up time spent in hospital. Multivariable models were adjusted for relevant baseline characteristics.

Results: The 1549 SLE patients eligible for this analysis were mostly female (88.7%) with mean (SD) age 35.7 (13.3) years and median (IQR) disease duration 1.2 (0.9-1.5) years at baseline. Mean (SD) baseline SLICC-FI was 0.17 (0.08). During mean (SD) follow-up of 7.2 (3.7) years, 614 patients (39.6%) experienced 1570 hospitalizations. Higher baseline SLICC-FI values (per 0.05 increment) were associated with more frequent hospitalizations during follow-up (Incidence Rate Ratio 1.21; 95%CI 1.13-1.30), adjusting for baseline age, sex, corticosteroid use, immunosuppressive use, ethnicity/location, SLE disease activity index 2000 (SLEDAI-2K), SLICC/ACR damage index (SDI), and disease duration. Among patients with ≥1 hospitalization, higher baseline SLICC-FI values predicted a greater proportion of follow-up time spent hospitalized (Relative Rate 1.09; 95%CI 1.02-1.16).

Conclusion: The SLICC-FI predicts future hospitalizations among incident SLE patients, further supporting the SLICC-FI as a valid health measure in SLE.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/acr.24504DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096857PMC
November 2020

Examining Racial Differences in Access to Primary Care for People Living with Lupus: Use of Ambulatory Care Sensitive Conditions to Measure Access.

Ethn Dis 2020 24;30(4):611-620. Epub 2020 Sep 24.

Department of Public Health Sciences, College of Medicine, MUSC, Charleston, SC.

Background: People living with lupus may experience poor access to primary care and delayed specialty care.

Purpose: To identify characteristics that lead to increased odds of poor access to primary care for minorities hospitalized with lupus.

Methods: Cross-sectional design with 2011-2012 hospitalization data from South Carolina, North Carolina, and Florida. We used ICD-9 codes to identify lupus hospitalizations. Ambulatory care sensitive conditions were used to identify preventable lupus hospitalizations and measure access to primary care. Logistic regression was used to estimate the odds ratio for the association between predictors and having poor access to primary care. Sensitivity analysis excluded patients aged >65 years.

Results: There were 23,154 total lupus hospitalizations, and 2,094 (9.04%) were preventable. An adjusted model showed minorities aged ≥65 years (OR 2.501, CI 1.501, 4.169), minorities aged 40-64 years (OR 2.248, CI: 1.394, 3.627), minorities with Medicare insurance (OR 1.669, CI:1.353,2.059) and minorities with Medicaid (OR 1.662,CI:1.321, 2.092) had the highest odds for a preventable lupus hospitalization. Minorities with Medicare had significantly higher odds for ≥3 hospital days (OR 1.275, CI: 1.149, 1.415). Whites with Medicare (OR 1.291, CI: 1.164, 1.432) had the highest odds for ≥3 days.

Conclusions: Our data show that middle-aged minorities living with lupus and on public health insurance have a higher likelihood of poor access to primary care. Health care workers and policymakers should develop plans to identify patients, explore issues affecting access, and place patients with a community health worker or social worker to promote better access to primary care.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18865/ed.30.4.611DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7518530PMC
April 2021

Performance of the 2019 EULAR/ACR classification criteria for systemic lupus erythematosus in early disease, across sexes and ethnicities.

Ann Rheum Dis 2020 10 14;79(10):1333-1339. Epub 2020 Aug 14.

Rheumatology, Azienda Ospedaliero Universitaria Pisana, Pisa, Toscana, Italy.

Objectives: The European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) 2019 Classification Criteria for systemic lupus erythematosus (SLE) have been validated with high sensitivity and specificity. We evaluated the performance of the new criteria with regard to disease duration, sex and race/ethnicity, and compared its performance against the Systemic Lupus International Collaborating Clinics (SLICC) 2012 and ACR 1982/1997 criteria.

Methods: Twenty-one SLE centres from 16 countries submitted SLE cases and mimicking controls to form the validation cohort. The sensitivity and specificity of the EULAR/ACR 2019, SLICC 2012 and ACR 1982/1997 criteria were evaluated.

Results: The cohort consisted of female (n=1098), male (n=172), Asian (n=118), black (n=68), Hispanic (n=124) and white (n=941) patients; with an SLE duration of 1 to <3 years (n=196) and ≥5 years (n=879). Among patients with 1 to <3 years disease duration, the EULAR/ACR criteria had better sensitivity than the ACR criteria (97% vs 81%). The EULAR/ACR criteria performed well in men (sensitivity 93%, specificity 96%) and women (sensitivity 97%, specificity 94%). Among women, the EULAR/ACR criteria had better sensitivity than the ACR criteria (97% vs 83%) and better specificity than the SLICC criteria (94% vs 82%). Among white patients, the EULAR/ACR criteria had better sensitivity than the ACR criteria (95% vs 83%) and better specificity than the SLICC criteria (94% vs 83%). The EULAR/ACR criteria performed well among black patients (sensitivity of 98%, specificity 100%), and had better sensitivity than the ACR criteria among Hispanic patients (100% vs 86%) and Asian patients (97% vs 77%).

Conclusions: The EULAR/ACR 2019 criteria perform well among patients with early disease, men, women, white, black, Hispanic and Asian patients. These criteria have superior sensitivity than the ACR criteria and/or superior specificity than the SLICC criteria across many subgroups.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/annrheumdis-2020-217162DOI Listing
October 2020

Cancer risk in a large inception SLE cohort: Effects of demographics, smoking, and medications.

Arthritis Care Res (Hoboken) 2020 Aug 19. Epub 2020 Aug 19.

Department of Rheumatology, Center for Rheumatology Research Fossvogur, Landspitali University Hospital, Reykjavik, Iceland.

Objective: To assess cancer risk factors in incident SLE.

Methods: Clinical variables and cancer outcomes were assessed annually among incident SLE patients. Multivariate hazard regression models (over-all risk, and most common cancers) included demographics and time-dependent medications (corticosteroids, antimalarial drugs, immunosuppressants), smoking, and adjusted mean SLE Disease Activity Index-2K.

Results: Among 1668 patients (average 9 years follow-up), 65 cancers occurred: 15 breast, 10 non-melanoma skin, seven lung, six hematological, six prostate, five melanoma, three cervical, three renal, two each gastric, head and neck, and thyroid, and one each rectal, sarcoma, thymoma, and uterine cancers. Half of cancers (including all lung cancers) occurred in past/current smokers, versus one-third of patients without cancer. Multivariate analyses indicated over-all cancer risk was related primarily to male sex and older age at SLE diagnosis. In addition, smoking was associated with lung cancer. For breast cancer risk, age was positively and anti-malarial drugs were negatively associated. Anti-malarial drugs and higher disease activity were also negatively associated with non-melanoma skin cancer (NMSC) risk, whereas age and cyclophosphamide were positively associated. Disease activity was associated positively with hematologic and negatively with NMSC risk.

Conclusions: Smoking is a key modifiable risk factor, especially for lung cancer, in SLE. Immunosuppressive medications were not clearly associated with higher risk except for cyclophosphamide and NMSC. Antimalarials were negatively associated with breast cancer and NMSC risk. SLE activity was associated positively with hematologic cancer and negatively with NMSC. Since the absolute number of cancers was small, additional follow-up will help consolidate these findings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/acr.24425DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7892637PMC
August 2020

Phase II Randomized Trial of Rituximab Plus Cyclophosphamide Followed by Belimumab for the Treatment of Lupus Nephritis.

Arthritis Rheumatol 2021 01 1;73(1):121-131. Epub 2020 Dec 1.

University of California, San Francisco.

Objective: To assess the safety, mechanism of action, and preliminary efficacy of rituximab followed by belimumab in the treatment of refractory lupus nephritis (LN).

Methods: In a multicenter, randomized, open-label clinical trial, 43 patients with recurrent or refractory LN were treated with rituximab, cyclophosphamide (CYC), and glucocorticoids followed by weekly belimumab infusions until week 48 (RCB group), or treated with rituximab and CYC but no belimumab infusions (RC group). Patients were followed up until week 96. Percentages of total and autoreactive B cell subsets in the patients' peripheral blood were analyzed by flow cytometry.

Results: Treatment with belimumab did not increase the incidence of adverse events in patients with refractory LN. At week 48, a complete or partial renal response occurred in 11 (52%) of 21 patients receiving belimumab, compared to 9 (41%) of 22 patients in the RC group who did not receive belimumab (P = 0.452). Lack of improvement in or worsening of LN was the major reason for treatment failure. B cell depletion occurred in both groups, but the percentage of B cells remained lower in those receiving belimumab (geometric mean number of B cells at week 60, 53 cells/μl in the RCB group versus 11 cells/μl in the RC group; P = 0.0012). Percentages of total and autoreactive transitional B cells increased from baseline to week 48 in both groups. However, percentages of total and autoreactive naive B cells decreased from baseline to week 48 in the belimumab group compared to the no belimumab RC group (P = 0.0349), a finding that is consistent with the observed impaired maturation of naive B cells and enhanced censoring of autoreactive B cells.

Conclusion: The addition of belimumab to a treatment regimen with rituximab and CYC was safe in patients with refractory LN. This regimen diminished maturation of transitional to naive B cells during B cell reconstitution, and enhanced the negative selection of autoreactive B cells. Clinical efficacy was not improved with rituximab and CYC in combination with belimumab when compared to a therapeutic strategy of B cell depletion alone in patients with LN.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/art.41466DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7839443PMC
January 2021

Accrual of Atherosclerotic Vascular Events in a Multicenter Inception Systemic Lupus Erythematosus Cohort.

Arthritis Rheumatol 2020 10 25;72(10):1734-1740. Epub 2020 Aug 25.

Hairmyres Hospital, East Kilbride, Scotland, UK.

Objective: In previous studies, atherosclerotic vascular events (AVEs) were shown to occur in ~10% of patients with systemic lupus erythematosus (SLE). We undertook this study to investigate the annual occurrence and potential risk factors for AVEs in a multinational, multiethnic inception cohort of patients with SLE.

Methods: A large 33-center cohort of SLE patients was followed up yearly between 1999 and 2017. AVEs were attributed to atherosclerosis based on SLE being inactive at the time of the AVE as well as typical atherosclerotic changes observed on imaging or pathology reports and/or evidence of atherosclerosis elsewhere. Analyses included descriptive statistics, rate of AVEs per 1,000 patient-years, and univariable and multivariable relative risk regression models.

Results: Of the 1,848 patients enrolled in the cohort, 1,710 had ≥1 follow-up visit after enrollment, for a total of 13,666 patient-years. Of these 1,710 patients, 3.6% had ≥1 AVEs attributed to atherosclerosis, for an event rate of 4.6 per 1,000 patient-years. In multivariable analyses, lower AVE rates were associated with antimalarial treatment (hazard ratio [HR] 0.54 [95% confidence interval (95% CI) 0.32-0.91]), while higher AVE rates were associated with any prior vascular event (HR 4.00 [95% CI 1.55-10.30]) and a body mass index of >40 kg/m (HR 2.74 [95% CI 1.04-7.18]). A prior AVE increased the risk of subsequent AVEs (HR 5.42 [95% CI 3.17-9.27], P < 0.001).

Conclusion: The prevalence of AVEs and the rate of AVE accrual demonstrated in the present study is much lower than that seen in previously published data. This may be related to better control of both the disease activity and classic risk factors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/art.41392DOI Listing
October 2020

Comparison of the 2019 European Alliance of Associations for Rheumatology/American College of Rheumatology Systemic Lupus Erythematosus Classification Criteria With Two Sets of Earlier Systemic Lupus Erythematosus Classification Criteria.

Arthritis Care Res (Hoboken) 2020 May 20. Epub 2020 May 20.

Kantonsspital, Schaffhausen, Switzerland.

Objective: The Systemic Lupus International Collaborating Clinics (SLICC) 2012 systemic lupus erythematosus (SLE) classification criteria and the revised American College of Rheumatology (ACR) 1997 criteria are list based, counting each SLE manifestation equally. We derived a classification rule based on giving variable weights to the SLICC criteria and compared its performance to the revised ACR 1997, the unweighted SLICC 2012, and the newly reported European Alliance of Associations for Rheumatology (EULAR)/ACR 2019 criteria sets.

Methods: The physician-rated patient scenarios used to develop the SLICC 2012 classification criteria were reemployed to devise a new weighted classification rule using multiple linear regression. The performance of the rule was evaluated on an independent set of expert-diagnosed patient scenarios and compared to the performance of the previously reported classification rules.

Results: The weighted SLICC criteria and the EULAR/ACR 2019 criteria had less sensitivity but better specificity compared to the list-based revised ACR 1997 and SLICC 2012 classification criteria. There were no statistically significant differences between any pair of rules with respect to overall agreement with the physician diagnosis.

Conclusion: The 2 new weighted classification rules did not perform better than the existing list-based rules in terms of overall agreement on a data set originally generated to assess the SLICC criteria. Given the added complexity of summing weights, researchers may prefer the unweighted SLICC criteria. However, the performance of a classification rule will always depend on the populations from which the cases and non-cases are derived and whether the goal is to prioritize sensitivity or specificity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/acr.24263DOI Listing
May 2020

Neuropsychiatric events in systemic lupus erythematosus: a longitudinal analysis of outcomes in an international inception cohort using a multistate model approach.

Ann Rheum Dis 2020 03 8;79(3):356-362. Epub 2020 Jan 8.

Copenhagen Lupus and Vasculitis Clinic, 4242, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.

Objectives: Using a reversible multistate model, we prospectively examined neuropsychiatric (NP) events for attribution, outcome and association with health-related quality of life (HRQoL), in an international, inception cohort of systemic lupus erythematosus (SLE) patients.

Methods: Annual assessments for 19 NP events attributed to SLE and non-SLE causes, physician determination of outcome and patient HRQoL (short-form (SF)-36 scores) were measured. Time-to-event analysis and multistate modelling examined the onset, recurrence and transition between NP states.

Results: NP events occurred in 955/1827 (52.3%) patients and 592/1910 (31.0%) unique events were attributed to SLE. In the first 2 years of follow-up the relative risk (95% CI) for SLE NP events was 6.16 (4.96, 7.66) and non-SLE events was 4.66 (4.01, 5.43) compared with thereafter. Patients without SLE NP events at initial assessment had a 74% probability of being event free at 10 years. For non-SLE NP events the estimate was 48%. The majority of NP events resolved over 10 years but mortality was higher in patients with NP events attributed to SLE (16%) versus patients with no NPSLE events (6%) while the rate was comparable in patients with non-SLE NP events (7%) compared with patients with no non-SLE events (6%). Patients with NP events had lower SF-36 summary scores compared with those without NP events and resolved NP states (p<0.001).

Conclusions: NP events occur most frequently around the diagnosis of SLE. Although the majority of events resolve they are associated with reduced HRQoL and excess mortality. Multistate modelling is well suited for the assessment of NP events in SLE.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/annrheumdis-2019-216150DOI Listing
March 2020

Prediction of Damage Accrual in Systemic Lupus Erythematosus Using the Systemic Lupus International Collaborating Clinics Frailty Index.

Arthritis Rheumatol 2020 04 12;72(4):658-666. Epub 2020 Feb 12.

Emory University School of Medicine, Atlanta, Georgia.

Objective: The Systemic Lupus International Collaborating Clinics (SLICC) frailty index (FI) has been shown to predict mortality, but its association with other important outcomes is unknown. We examined the association of baseline SLICC FI values with damage accrual in the SLICC inception cohort.

Methods: The baseline visit was defined as the first visit at which both organ damage (SLICC/American College of Rheumatology Damage Index [SDI]) and health-related quality of life (Short Form 36) were assessed. Baseline SLICC FI scores were calculated. Damage accrual was measured by the increase in SDI between the baseline assessment and the last study visit. Multivariable negative binomial regression was used to estimate the association between baseline SLICC FI values and the rate of increase in the SDI during follow-up, adjusting for relevant demographic and clinical characteristics.

Results: The 1,549 systemic lupus erythematosus (SLE) patients eligible for this analysis were mostly female (88.7%) with a mean ± SD age of 35.7 ± 13.3 years and a median disease duration of 1.2 years (interquartile range 0.9-1.5 years) at baseline. The mean ± SD baseline SLICC FI was 0.17 ± 0.08. Over a mean ± SD follow-up of 7.2 ± 3.7 years, 653 patients (42.2%) had an increase in SDI. Higher baseline SLICC FI values (per 0.05 increase) were associated with higher rates of increase in the SDI during follow-up (incidence rate ratio [IRR] 1.19 [95% confidence interval 1.13-1.25]), after adjusting for age, sex, ethnicity/region, education, baseline SLE Disease Activity Index 2000, baseline SDI, and baseline use of glucocorticoids, antimalarials, and immunosuppressive agents.

Conclusion: Our findings indicate that the SLICC FI predicts damage accrual in incident SLE, which further supports the SLICC FI as a valid health measure in SLE.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/art.41144DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7113092PMC
April 2020

Soluble urokinase plasminogen activator receptor (suPAR) levels predict damage accrual in patients with recent-onset systemic lupus erythematosus.

J Autoimmun 2020 01 17;106:102340. Epub 2019 Oct 17.

Department of Clinical Sciences Lund, Section of Rheumatology, Lund University, Lund, Sweden.

Objective: The soluble urokinase plasminogen activator receptor (suPAR) has potential as a prognosis and severity biomarker in several inflammatory and infectious diseases. In a previous cross-sectional study, suPAR levels were shown to reflect damage accrual in cases of systemic lupus erythematosus (SLE). Herein, we evaluated suPAR as a predictor of future organ damage in recent-onset SLE.

Methods: Included were 344 patients from the Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort who met the 1997 American College of Rheumatology classification criteria with 5-years of follow-up data available. Baseline sera from patients and age- and sex-matched controls were assayed for suPAR. Organ damage was assessed annually using the SLICC/ACR damage index (SDI).

Results: The levels of suPAR were higher in patients who accrued damage, particularly those with SDI≥2 at 5 years (N = 32, 46.8% increase, p = 0.004), as compared to patients without damage. Logistic regression analysis revealed a significant impact of suPAR on SDI outcome (SDI≥2; OR = 1.14; 95% CI 1.03-1.26), also after adjustment for confounding factors. In an optimized logistic regression to predict damage, suPAR persisted as a predictor, together with baseline disease activity (SLEDAI-2K), age, and non-Caucasian ethnicity (model AUC = 0.77). Dissecting SDI into organ systems revealed higher suPAR levels in patients who developed musculoskeletal damage (SDI≥1; p = 0.007).

Conclusion: Prognostic biomarkers identify patients who are at risk of acquiring early damage and therefore need careful observation and targeted treatment strategies. Overall, suPAR constitutes an interesting biomarker for patient stratification and for identifying SLE patients who are at risk of acquiring organ damage during the first 5 years of disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaut.2019.102340DOI Listing
January 2020

Economic Evaluation of Damage Accrual in an International Systemic Lupus Erythematosus Inception Cohort Using a Multistate Model Approach.

Arthritis Care Res (Hoboken) 2020 12;72(12):1800-1808

Hairmyres Hospital, East Kilbride, Scotland, UK.

Objective: There is a paucity of data regarding health care costs associated with damage accrual in systemic lupus erythematosus. The present study was undertaken to describe costs associated with damage states across the disease course using multistate modeling.

Methods: Patients from 33 centers in 11 countries were enrolled in the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort within 15 months of diagnosis. Annual data on demographics, disease activity, damage (SLICC/American College of Rheumatology Damage Index [SDI]), hospitalizations, medications, dialysis, and selected procedures were collected. Ten-year cumulative costs (Canadian dollars) were estimated by multiplying annual costs associated with each SDI state by the expected state duration using a multistate model.

Results: A total of 1,687 patients participated; 88.7% were female, 49.0% were white, mean ± SD age at diagnosis was 34.6 ± 13.3 years, and mean time to follow-up was 8.9 years (range 0.6-18.5 years). Mean annual costs were higher for those with higher SDI scores as follows: $22,006 (Canadian) (95% confidence interval [95% CI] $16,662, $27,350) for SDI scores ≥5 versus $1,833 (95% CI $1,134, $2,532) for SDI scores of 0. Similarly, 10-year cumulative costs were higher for those with higher SDI scores at the beginning of the 10-year interval as follows: $189,073 (Canadian) (95% CI $142,318, $235,827) for SDI scores ≥5 versus $21,713 (95% CI $13,639, $29,788) for SDI scores of 0.

Conclusion: Patients with the highest SDI scores incur 10-year cumulative costs that are ~9-fold higher than those with the lowest SDI scores. By estimating the damage trajectory and incorporating annual costs, data on damage can be used to estimate future costs, which is critical knowledge for evaluating the cost-effectiveness of novel therapies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/acr.24092DOI Listing
December 2020

Effect of vitamin D on serum markers of bone turnover in SLE in a randomised controlled trial.

Lupus Sci Med 2019 17;6(1):e000352. Epub 2019 Sep 17.

Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital, Boston, Massachusetts, USA.

Objective: Bone health in SLE is adversely affected by vitamin D deficiency, inflammatory cytokines and glucocorticoid use. We hypothesised that vitamin D supplementation would increase markers of bone formation and decrease markers of bone resorption in SLE subjects.

Methods: We studied 43 vitamin D-deficient SLE subjects who participated in a 12-week randomised controlled trial of 2000-4000 IU/day vitamin D supplementation versus placebo. Subjects had inactive SLE (SLE Disease Activity Index ≤4) and were taking <20 mg prednisone daily at baseline. We assayed baseline and week 12 serum 25-hydroxyvitamin D, N-terminal propeptide of type 1 collagen (P1NP) and C-telopeptide (CTX). We tested the effect of vitamin D versus placebo on change (Δ) in P1NP and ΔCTX in an intention-to-treat analysis. Secondary analyses evaluated whether vitamin D affected bone turnover among subjects achieving vitamin D repletion (≥30 ng/mL) or currently taking glucocorticoids.

Results: 28 subjects were randomised to vitamin D and 15 to placebo. Mean age was 39 years and 40% were using glucocorticoids at enrolment. Repletion was achieved by 46% in the vitamin D group versus none in the placebo group. Changes in bone turnover markers were not significantly different in the vitamin D group versus placebo group (median ΔP1NP -0.2 vitamin D group vs -1.1 placebo group (p=0.83); median ΔCTX +3.5 vitamin D group vs -37.0 placebo group (p=0.50)). The effect of vitamin D did not differ based on achieving vitamin D repletion or baseline glucocorticoid use.

Conclusion: Vitamin D supplementation did not affect the 12-week change in bone turnover markers among SLE subjects in this trial.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/lupus-2019-000352DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6762038PMC
September 2019

Peripheral Nervous System Disease in Systemic Lupus Erythematosus: Results From an International Inception Cohort Study.

Arthritis Rheumatol 2020 01 28;72(1):67-77. Epub 2019 Nov 28.

Amsterdam University Medical Centers, Amsterdam, The Netherlands.

Objective: To determine the frequency, clinical characteristics, associations, and outcomes of different types of peripheral nervous system (PNS) disease in a multiethnic/multiracial, prospective inception cohort of systemic lupus erythematosus (SLE) patients.

Methods: Patients were evaluated annually for 19 neuropsychiatric (NP) events including 7 types of PNS disease. SLE disease activity, organ damage, autoantibodies, and patient and physician assessment of outcome were measured. Time to event and linear regressions were used as appropriate.

Results: Of 1,827 SLE patients, 88.8% were female, and 48.8% were white. The mean ± SD age was 35.1 ± 13.3 years, disease duration at enrollment was 5.6 ± 4.2 months, and follow-up was 7.6 ± 4.6 years. There were 161 PNS events in 139 (7.6%) of 1,827 patients. The predominant events were peripheral neuropathy (66 of 161 [41.0%]), mononeuropathy (44 of 161 [27.3%]), and cranial neuropathy (39 of 161 [24.2%]), and the majority were attributed to SLE. Multivariate Cox regressions suggested longer time to resolution in patients with a history of neuropathy, older age at SLE diagnosis, higher SLE Disease Activity Index 2000 scores, and for peripheral neuropathy versus other neuropathies. Neuropathy was associated with significantly lower Short Form 36 (SF-36) physical and mental component summary scores versus no NP events. According to physician assessment, the majority of neuropathies resolved or improved over time, which was associated with improvements in SF-36 summary scores for peripheral neuropathy and mononeuropathy.

Conclusion: PNS disease is an important component of total NPSLE and has a significant negative impact on health-related quality of life. The outcome is favorable for most patients, but our findings indicate that several factors are associated with longer time to resolution.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/art.41070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6935421PMC
January 2020

2019 European League Against Rheumatism/American College of Rheumatology Classification Criteria for Systemic Lupus Erythematosus.

Arthritis Rheumatol 2019 09 6;71(9):1400-1412. Epub 2019 Aug 6.

Azienda Ospedaliero Universitaria Pisana, University of Pisa, Pisa, Italy.

Objective: To develop new classification criteria for systemic lupus erythematosus (SLE) jointly supported by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR).

Methods: This international initiative had four phases. 1) Evaluation of antinuclear antibody (ANA) as an entry criterion through systematic review and meta-regression of the literature and criteria generation through an international Delphi exercise, an early patient cohort, and a patient survey. 2) Criteria reduction by Delphi and nominal group technique exercises. 3) Criteria definition and weighting based on criterion performance and on results of a multi-criteria decision analysis. 4) Refinement of weights and threshold scores in a new derivation cohort of 1,001 subjects and validation compared with previous criteria in a new validation cohort of 1,270 subjects.

Results: The 2019 EULAR/ACR classification criteria for SLE include positive ANA at least once as obligatory entry criterion; followed by additive weighted criteria grouped in 7 clinical (constitutional, hematologic, neuropsychiatric, mucocutaneous, serosal, musculoskeletal, renal) and 3 immunologic (antiphospholipid antibodies, complement proteins, SLE-specific antibodies) domains, and weighted from 2 to 10. Patients accumulating ≥10 points are classified. In the validation cohort, the new criteria had a sensitivity of 96.1% and specificity of 93.4%, compared with 82.8% sensitivity and 93.4% specificity of the ACR 1997 and 96.7% sensitivity and 83.7% specificity of the Systemic Lupus International Collaborating Clinics 2012 criteria.

Conclusion: These new classification criteria were developed using rigorous methodology with multidisciplinary and international input, and have excellent sensitivity and specificity. Use of ANA entry criterion, hierarchically clustered, and weighted criteria reflects current thinking about SLE and provides an improved foundation for SLE research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/art.40930DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6827566PMC
September 2019

2019 European League Against Rheumatism/American College of Rheumatology classification criteria for systemic lupus erythematosus.

Ann Rheum Dis 2019 09 5;78(9):1151-1159. Epub 2019 Aug 5.

Department of Clinical and Experimental Medicine, Rheumatology Unit, Azienda Ospedaliero Universitaria Pisana, University of Pisa, Pisa, Italy.

Objective: To develop new classification criteria for systemic lupus erythematosus (SLE) jointly supported by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR).

Methods: This international initiative had four phases. (1) Evaluation of antinuclear antibody (ANA) as an entry criterion through systematic review and meta-regression of the literature and criteria generation through an international Delphi exercise, an early patient cohort and a patient survey. (2) Criteria reduction by Delphi and nominal group technique exercises. (3) Criteria definition and weighting based on criterion performance and on results of a multi-criteria decision analysis. (4) Refinement of weights and threshold scores in a new derivation cohort of 1001 subjects and validation compared with previous criteria in a new validation cohort of 1270 subjects.

Results: The 2019 EULAR/ACR classification criteria for SLE include positive ANA at least once as obligatory entry criterion; followed by additive weighted criteria grouped in seven clinical (constitutional, haematological, neuropsychiatric, mucocutaneous, serosal, musculoskeletal, renal) and three immunological (antiphospholipid antibodies, complement proteins, SLE-specific antibodies) domains, and weighted from 2 to 10. Patients accumulating ≥10 points are classified. In the validation cohort, the new criteria had a sensitivity of 96.1% and specificity of 93.4%, compared with 82.8% sensitivity and 93.4% specificity of the ACR 1997 and 96.7% sensitivity and 83.7% specificity of the Systemic Lupus International Collaborating Clinics 2012 criteria.

Conclusion: These new classification criteria were developed using rigorous methodology with multidisciplinary and international input, and have excellent sensitivity and specificity. Use of ANA entry criterion, hierarchically clustered and weighted criteria reflect current thinking about SLE and provide an improved foundation for SLE research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/annrheumdis-2018-214819DOI Listing
September 2019

META-ANALYSIS OF DOLPHIN AND HUMAN PERIPHERAL BLOOD MONONUCLEAR CELLS REVEALS INFLAMMATORY SIGNATURES ASSOCIATED WITH EXPOSURE TO HIGH LEVELS OF PERFLUOROALKYL SUBSTANCES.

Int J Adv Sci Eng Technol 2019 Jul;7(3):66-72

Department of Medicine, MUSC. USA, School of Biological Sciences & Institute for Global Food Security, Queens University Belfast, Belfast, UK.

Currently a fundamental gap exists on how persistent organic pollutants affect humans especially those who consume high levels of seafood from contaminated coastal waters. There is an urgent need to better understand effects of these contaminants on human health in coastal communities. Elevated contaminant levels in coastal seafood will give rise to increased contaminant burdens in humans who consume coastal seafood and given the toxicity of these contaminants increase risk for immune system disorders. In this paper we describe how we assessed the effects of contaminant exposures using high-throughput RNA sequencing (RNA-seq) in peripheral blood mononuclear cells from two species, dolphins and humans. This paper presents an integrated systems biology approach to understand the adverse effects of one of these CECs PFAS on both species.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8248928PMC
July 2019

Association of Epstein-Barr virus serological reactivation with transitioning to systemic lupus erythematosus in at-risk individuals.

Ann Rheum Dis 2019 09 19;78(9):1235-1241. Epub 2019 Jun 19.

Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA

Objective: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with unknown aetiology. Epstein-Barr virus (EBV) is an environmental factor associated with SLE. EBV maintains latency in B cells with frequent reactivation measured by antibodies against viral capsid antigen (VCA) and early antigen (EA). In this study, we determined whether EBV reactivation and single nucleotide polymorphisms (SNPs) in EBV-associated host genes are associated with SLE transition.

Methods: SLE patient relatives (n=436) who did not have SLE at baseline were recontacted after 6.3 (±3.9) years and evaluated for interim transitioning to SLE (≥4 cumulative American College of Rheumatology criteria); 56 (13%) transitioned to SLE prior to the follow-up visit. At both visits, detailed demographic, environmental, clinical information and blood samples were obtained. Antibodies against viral antigens were measured by ELISA. SNPs in , , and genes were typed by ImmunoChip. Generalised estimating equations were used to test associations between viral antibody levels and transitioning to SLE.

Results: Mean baseline VCA IgG (4.879±1.797 vs 3.866±1.795, p=0.0003) and EA IgG (1.192±1.113 vs 0.7774±0.8484, p=0.0236) levels were higher in transitioned compared with autoantibody negative non-transitioned relatives. Increased VCA IgG and EA IgG were associated with transitioning to SLE (OR 1.28 95% CI 1.07 to 1.53, p=0.007, OR 1.43 95% CI 1.06 to 1.93, p=0.02, respectively). Significant interactions were observed between variant rs48100485 and VCA IgG levels and variant rs3024493 and VCA IgA levels in transitioning to SLE.

Conclusion: Heightened serologic reactivation of EBV increases the probability of transitioning to SLE in unaffected SLE relatives.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/annrheumdis-2019-215361DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6692217PMC
September 2019

The immune cell landscape in kidneys of patients with lupus nephritis.

Nat Immunol 2019 07 17;20(7):902-914. Epub 2019 Jun 17.

Division of Rheumatology, Johns Hopkins University, Baltimore, MD, USA.

Lupus nephritis is a potentially fatal autoimmune disease for which the current treatment is ineffective and often toxic. To develop mechanistic hypotheses of disease, we analyzed kidney samples from patients with lupus nephritis and from healthy control subjects using single-cell RNA sequencing. Our analysis revealed 21 subsets of leukocytes active in disease, including multiple populations of myeloid cells, T cells, natural killer cells and B cells that demonstrated both pro-inflammatory responses and inflammation-resolving responses. We found evidence of local activation of B cells correlated with an age-associated B-cell signature and evidence of progressive stages of monocyte differentiation within the kidney. A clear interferon response was observed in most cells. Two chemokine receptors, CXCR4 and CX3CR1, were broadly expressed, implying a potentially central role in cell trafficking. Gene expression of immune cells in urine and kidney was highly correlated, which would suggest that urine might serve as a surrogate for kidney biopsies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41590-019-0398-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6726437PMC
July 2019

Cell of origin in diffuse large B-cell lymphoma in systemic lupus erythematosus: molecular and clinical factors associated with survival.

Lupus Sci Med 2019 4;6(1):e000324. Epub 2019 May 4.

Division of Clinical Epidemiology, McGill University Health Centre, Montreal, Québec, Canada.

Background: SLE is associated with increased risk of diffuse large B-cell lymphoma (DLBCL). DLBCL is routinely classified by cell of origin (COO), with germinal centre B-cell (GCB) being more common and indicating better prognosis in the general population. We studied COO subtyping in patients with SLE diagnosed with DLBCL and their survival.

Patients And Methods: We evaluated 20 cases of SLE with DLBCL. Immunohistochemistry analysis was performed (BCL2, MYC, BCL6, CD10, CD20, FOXP1, GCET1, MUM1) in tissue microarrays. We examined associations between molecular and clinical features, including overall survival.

Results: Of the 20 DLBCL SLE cases, 12/20 cases (60%) were classified as non-GCB using Hans or Choi algorithms. MYC and BCL2 protein expression was positive in 6/20 (30%) and 8/20 (40%) SLE cases, respectively, with 2/20 (10%) co-expressing both markers. Seven (7/20) had only extranodal involvement at DLBCL diagnosis. As expected, non-GCB cases had worse survival. Cases presenting exclusively with extranodal disease were associated with shorter SLE duration and better survival despite higher BCL2 protein expression.

Conclusions: We present novel data characterising DLBCL in SLE. Sixty per cent of the DLBCL in patients with SLE were non-GCB. The nodal and extranodal distribution in SLE was similar to what is known in the general population, but extranodal disease occurred more often with short SLE duration and was associated with longer overall survival. More research on cancer in SLE is the key to further understanding the complex interplay between cancer and the immune system.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/lupus-2019-000324DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6541753PMC
May 2019

Progesterone decreases gut permeability through upregulating occludin expression in primary human gut tissues and Caco-2 cells.

Sci Rep 2019 06 10;9(1):8367. Epub 2019 Jun 10.

Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, 29425, USA.

Progesterone plays a protective role in preventing inflammation and preterm delivery during pregnancy. However, the mechanism involved is unknown. Microbial product translocation from a permeable mucosa is demonstrated as a driver of inflammation. To study the mechanism of the protective role of progesterone during pregnancy, we investigated the effect of physiologic concentrations of progesterone on tight junction protein occludin expression and human gut permeability in vitro and systemic microbial translocation in pregnant women in vivo. Plasma bacterial lipopolysaccharide (LPS), a representative marker of in vivo systemic microbial translocation was measured. We found that plasma LPS levels were significantly decreased during 24 to 28 weeks of gestation compared to 8 to 12 weeks of gestation. Moreover, plasma LPS levels were negatively correlated with plasma progesterone levels but positively correlated with plasma tumor necrosis factor-alpha (TNF-α) levels at 8 to 12 weeks of gestation but not at 24 to 28 weeks of gestation. Progesterone treatment increased intestinal trans-epithelial electrical resistance (TEER) in primary human colon tissues and Caco-2 cells in vitro through upregulating tight junction protein occludin expression. Furthermore, progesterone exhibited an inhibitory effect on nuclear factor kappa B (NF-κB) activation following LPS stimulation in Caco-2 cells. These results reveal a novel mechanism that progesterone may play an important role in decreasing mucosal permeability, systemic microbial translocation, and inflammation during pregnancy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-019-44448-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6558054PMC
June 2019

A Link Between Plasma Microbial Translocation, Microbiome, and Autoantibody Development in First-Degree Relatives of Systemic Lupus Erythematosus Patients.

Arthritis Rheumatol 2019 11 27;71(11):1858-1868. Epub 2019 Sep 27.

Medical University of South Carolina, Charleston.

Objective: Systemic lupus erythematosus (SLE) is characterized by the production of antibodies against self antigens. However, the events underlying autoantibody formation in SLE remain unclear. This study was undertaken to investigate the role of plasma autoantibody levels, microbial translocation, and the microbiome in SLE.

Methods: Plasma samples from 2 cohorts, one with 18 unrelated healthy controls and 18 first-degree relatives and the other with 19 healthy controls and 21 SLE patients, were assessed for autoantibody levels by autoantigen microarray analysis, measurement of lipopolysaccharide (LPS) levels by Limulus amebocyte assay, and determination of microbiome composition by microbial 16S ribosomal DNA sequencing.

Results: First-degree relatives and SLE patients exhibited increased plasma autoantibody levels compared to their control groups. Parents and children of lupus patients exhibited elevated plasma LPS levels compared to controls (P = 0.02). Plasma LPS levels positively correlated with plasma anti-double-stranded DNA IgG levels in first-degree relatives (r = 0.51, P = 0.03), but not in SLE patients. Circulating microbiome analysis revealed that first-degree relatives had significantly reduced microbiome diversity compared to their controls (observed species, P = 0.004; Chao1 index, P = 0.005), but this reduction was not observed in SLE patients. The majority of bacteria that were differentially abundant between unrelated healthy controls and first-degree relatives were in the Firmicutes phylum, while differences in bacteria from several phyla were identified between healthy controls and SLE patients. Bacteria in the Paenibacillus genus were the only overlapping differentially abundant bacteria in both cohorts, and were reduced in first-degree relatives (adjusted P [P ] = 2.13 × 10 ) and SLE patients (P = 0.008) but elevated in controls.

Conclusions: These results indicate a possible role of plasma microbial translocation and microbiome composition in influencing autoantibody development in SLE.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/art.40935DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6817371PMC
November 2019

Construction of a Frailty Index as a Novel Health Measure in Systemic Lupus Erythematosus.

J Rheumatol 2020 01 15;47(1):72-81. Epub 2019 Apr 15.

From the Divisions of Rheumatology and Geriatric Medicine, Department of Medicine, Dalhousie University; Department of Community Health and Epidemiology, Dalhousie University, Halifax, Nova Scotia; Divisions of Rheumatology and Clinical Epidemiology, Department of Medicine, McGill University, Montreal; Division of Rheumatology, Centre Hospitalier Universitaire (CHU) de Québec et Université Laval, Quebec City, Quebec; Division of Rheumatology, Cumming School of Medicine, University of Calgary, Calgary, Alberta; Center for Prognosis Studies in the Rheumatic Diseases, Toronto Western Hospital and University of Toronto, Toronto, Ontario; University of Manitoba, Winnipeg, Manitoba; Division of Rheumatology, Department of Medicine and Department of Pathology, Queen Elizabeth II Health Sciences Center and Dalhousie University, Halifax, Nova Scotia, Canada; Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea; Rheumatology Research Group, School of Immunity and Infection, College of Medical and Dental Sciences, University of Birmingham, Birmingham; Arthritis Research UK Epidemiology Unit, Faculty of Biology Medicine and Health, Manchester Academic Health Sciences Center, The University of Manchester, and National Institute for Health Research (NIHR) Manchester Musculoskeletal Biomedical Research Centre, Manchester University National Health Service (NHS) Foundation Trust, Manchester Academic Health Science Center, Manchester; Center for Rheumatology, Department of Medicine, University College London, London; Lanarkshire Center for Rheumatology, Hairmyres Hospital, East Kilbride, Scotland; Lupus Research Unit, The Rayne Institute, St Thomas' Hospital, King's College London School of Medicine, London, UK; Instituto Nacional de Ciencias Medicas y Nutrición, Mexico City, Mexico; Cedars-Sinai/David Geffen School of Medicine at University of California Los Angeles (UCLA), Los Angeles, California; Department of Clinical Pharmacology, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma; Department of Medicine, State University of New York (SUNY) Downstate Medical Center, Brooklyn, New York; Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama; Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, Maryland; Thurston Arthritis Research Center, University of North Carolina, Chapel Hill, North Carolina; Northwestern University and Feinberg School of Medicine, Chicago, Illinois; Lupus Center of Excellence, Allegheny Health Network, Pittsburgh, Pennsylvania; Feinstein Institute for Medical Research, Manhasset, New York; Emory University School of Medicine, Division of Rheumatology, Atlanta, Georgia; Medical University of South Carolina, Charleston, South Carolina; University of California San Diego School of Medicine (UCSD), La Jolla, California; Hospital for Joint Diseases, New York University (NYU), Seligman Center for Advanced Therapeutics, New York, New York, USA; Autoimmune Diseases Research Unit, Department of Internal Medicine, BioCruces Health Research Institute, Hospital Universitario Cruces, University of the Basque Country, Barakaldo; Josep Font Autoimmune Diseases Laboratory, IDIBAPS, Department of Autoimmune Diseases, Hospital Clínic, Barcelona, Spain; Division of Rheumatology, Department of Internal Medicine, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey; Unit for Clinical Therapy Research (ClinTRID), Karolinska Institute, Stockholm; Department of Clinical Sciences Lund, Rheumatology, Lund University, Lund, Sweden; Copenhagen Lupus and Vasculitis Clinic, Section 4242, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.

Objective: To construct a Frailty Index (FI) as a measure of vulnerability to adverse outcomes among patients with systemic lupus erythematosus (SLE), using data from the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort.

Methods: The SLICC inception cohort consists of recently diagnosed patients with SLE followed annually with clinical and laboratory assessments. For this analysis, the baseline visit was defined as the first study visit at which sufficient information was available for construction of an FI. Following a standard procedure, variables from the SLICC database were evaluated as potential health deficits. Selected health deficits were then used to generate a SLICC-FI. The prevalence of frailty in the baseline dataset was evaluated using established cutpoints for FI values.

Results: The 1683 patients with SLE (92.1% of the overall cohort) eligible for inclusion in the baseline dataset were mostly female (89%) with mean (SD) age 35.7 (13.4) years and mean (SD) disease duration 18.8 (15.7) months at baseline. Of 222 variables, 48 met criteria for inclusion in the SLICC-FI. Mean (SD) SLICC-FI was 0.17 (0.08) with a range from 0 to 0.51. At baseline, 27.1% (95% CI 25.0-29.2) of patients were classified as frail, based on SLICC-FI values > 0.21.

Conclusion: The SLICC inception cohort permits feasible construction of an FI for use in patients with SLE. Even in a relatively young cohort of patients with SLE, frailty was common. The SLICC-FI may be a useful tool for identifying patients with SLE who are most vulnerable to adverse outcomes, but validation of this index is required prior to its use.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3899/jrheum.181338DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6800806PMC
January 2020
-->