Publications by authors named "Sébastien Sanges"

24 Publications

  • Page 1 of 1

Dyslipidemia is insufficiently treated in antiphospholipid syndrome patients.

Lupus 2022 Jul 13:9612033221114275. Epub 2022 Jul 13.

27023University of Lille, CHU Lille, Département de Médecine Interne et d'Immunologie Clinique, Centre National de Référence Maladies Systémiques et Auto-immunes Rares Nord et Nord-Ouest de France (CeRAINO), European Reference Network on Rare Connective Tissue and Musculoskeletal Diseases Network (ReCONNECT), Lille, France.

Objectives: Although dyslipidemia is a strong risk factor for thrombosis in antiphospholipid syndrome (APS), it has been poorly studied. This study aimed to assess lipids profile and risk factors for unachieved cholesterol levels in a real-life APS population.

Methods: Inclusion criteria were: APS diagnosis according to international classification criteria, referring to the out-patients clinic of our tertiary care center for their follow-up, and having a blood sample collection for lipids levels determination. Cholesterol level targets for each patient were defined according to 2019 ESC/EAS guidelines for the management of dyslipidemia.

Results: Between January 2020 and April 2021, 114 APS patients were included (male 37 (32.5%); mean age 49 ± 14 years). Among them, 40 (35.1%) had a history of dyslipidemia, 48 (42.1%) were under lipid-lowering therapies, and 59 (51.8%) had a history of cardiovascular disease (CVD). Mean levels of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride were, respectively, 110 ± 40 mg/dL, 60±20 mg/dL, and 120 (80-190) mg/dL. Unachieved LDL-C levels were found in 77 (67.5%) patients of whom 53 had history of CVD. Overall, 90 (78.9%) had protective HDL-C and 31 (27.2%) had hypertriglyceridemia. In the multivariate analysis, independent risk factors for unachieved LDL-C levels were older age and history of CVD; triple aPL negativity, defined as complete disappearance of aPL over time in APS patients who were previously positive in accordance to international criteria, was an independent protective factor for unachieved LDL-C.

Conclusion: Our finding suggested that dyslipidemia is frequent in APS patients and mainly insufficiently treated, especially in patients with history of CVD, who are at highest risk of future CV events.
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http://dx.doi.org/10.1177/09612033221114275DOI Listing
July 2022

Simple gene signature to assess murine fibroblast polarization.

Sci Rep 2022 Jul 11;12(1):11748. Epub 2022 Jul 11.

Inserm, U1286, 4Ème Étage Centre, Place Verdun, 59000, Lille, France.

We provide an original multi-stage approach identifying a gene signature to assess murine fibroblast polarization. Prototypic polarizations (inflammatory/fibrotic) were induced by seeded mouse embryonic fibroblasts (MEFs) with TNFα or TGFß1, respectively. The transcriptomic and proteomic profiles were obtained by RNA microarray and LC-MS/MS. Gene Ontology and pathways analysis were performed among the differentially expressed genes (DEGs) and proteins (DEPs). Balb/c mice underwent daily intradermal injections of HOCl (or PBS) as an experimental murine model of inflammation-mediated fibrosis in a time-dependent manner. As results, 1456 and 2215 DEGs, and 289 and 233 DEPs were respectively found in MEFs in response to TNFα or TGFß1, respectively. Among the most significant pathways, we combined 26 representative genes to encompass the proinflammatory and profibrotic polarizations of fibroblasts. Based on principal component analysis, this signature deciphered baseline state, proinflammatory polarization, and profibrotic polarization as accurately as RNA microarray and LC-MS/MS did. Then, we assessed the gene signature on dermal fibroblasts isolated from the experimental murine model. We observed a proinflammatory polarization at day 7, and a mixture of a proinflammatory and profibrotic polarizations at day 42 in line with histological findings. Our approach provides a small-size and convenient gene signature to assess murine fibroblast polarization.
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http://dx.doi.org/10.1038/s41598-022-15640-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9273630PMC
July 2022

Use of Biologics to Treat Relapsing and/or Refractory Polyarteritis Nodosa: Data from a European Collaborative Study.

Rheumatology (Oxford) 2022 Jun 10. Epub 2022 Jun 10.

Department of Internal Medicine, National Reference Center for Rare Systemic Autoimmune Diseases, AP-HP, APHP-CUP, Hôpital Cochin, Paris, 75014, France.

Objectives: To describe the effectiveness and safety of biologics for the treatment of relapsing and/or refractory polyarteritis nodosa (PAN).

Methods: A retrospective European collaborative study was conducted in patients with PAN who received biologics for relapsing and/or refractory disease.

Results: Forty-two patients with PAN received a total of 53 biological courses, including TNF-alpha blockers in 15 cases, rituximab (RTX) in 18 cases, tocilizumab (TCZ) in 10 cases, and other biologics in 10 cases. TNF-alpha blockers and TCZ were mainly used for refractory diseases whereas RTX was mainly initiated for relapsing disease. After a median follow-up of 29 (8-50) months, remission occurred in 40%, partial response in 13%, treatment failure in 40% and treatment discontinuation due to severe adverse events in 7% of patients receiving TNF-alpha blockers, 50%, none, 30% and 20% of TCZ recipients, and 33%, 11%, 56% and none of the RTX recipients, respectively. No remission was noted in patients treated with other biologics. Severe adverse events were observed in 14 (28%) patients without significant differences between the 3 biologics, leading to early biologics discontinuation in only 3 cases.

Conclusion: These results suggest that TCZ may be effective in relapsing and/or refractory PAN. Our data warrant further study to confirm these findings.
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http://dx.doi.org/10.1093/rheumatology/keac332DOI Listing
June 2022

Tolerance of bradykinin-releasing drugs in patients with acquired C1 inhibitor deficiency: a case series and review of the literature.

Eur J Dermatol 2022 02;32(1):49-55

CHU Lille, Département de Médecine Interne et Immunologie Clinique, F-59000 Lille, France, Centre de Référence des Angiœdèmes à Kinines, F-59000 Lille, France, University Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, F-59000 Lille, France, Inserm, F-59000 Lille, France.

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http://dx.doi.org/10.1684/ejd.2021.4175DOI Listing
February 2022

Initial characteristics and follow-up of patients with a diagnosis of angiotensin-converting enzyme inhibitor induced angioedema.

Allergy Asthma Proc 2022 03;43(2):155-162

From the Univ. Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, F-59000 Lille, France.

A differential diagnosis between angiotensin-converting enzyme inhibitor (ACEi) angioedema (AE) and histaminergic AE (hAE) might be challenging. Follow-up data may help discriminate these conditions but are scarcely reported. To report on the follow-up of patients with suspected ACEi-AE and to describe the baseline characteristics of AE attacks in patients with a diagnosis of ACEi-AE after follow-up. Sixty-four patients with suspected ACEi-AE (, with exposure to ACEi before the first attack, no urticaria associated, and normal C1-inhibitor levels) and at least one follow-up visit were included. Data were retrospectively collected at baseline and during the follow-up. After the follow-up, the diagnosis of ACEi-AE was probable in only 30 patients. The remaining patients were reclassified as having probable hAE (21 patients) or undetermined-mechanism AE (13 patients). Patients with ACEi-AE were mostly men (61%), with a median age of 64 years (interquartile range [IQR] ±17 years), with a highly variable delay from ACEi introduction (median: 23 months; interquartile range: 103 months). Attacks preferentially involved lips (50%), tongue (47%), and throat (30%). Interestingly, patients with probable ACEi-AE after a follow-up also frequently presented with a history of allergy and atopic conditions (20%), attacks with preferential evening onset (25%), and spontaneous resolution in < 24 hours (26%), which are usually considered as suggestive of hAE. ACEi-AE attacks responded to icatibant in 79% of the patients. Patients with probable ACEi-AE were mostly men with facial involvement. A third of the patients with an initial suspected diagnosis of ACEi-AE had a final diagnosis of probable hAE. Although a follow-up of all patients should be a standard of care, it is critical to the correct diagnosis in the case of suspected bradykinin-associated AE, which may actually be due to histamine.
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http://dx.doi.org/10.2500/aap.2022.43.220005DOI Listing
March 2022

Clinical phenotype and cytokine profile of adult IgA vasculitis with joint involvement.

Clin Rheumatol 2022 May 18;41(5):1483-1491. Epub 2022 Jan 18.

Department of Internal Medicine and Clinical Immunology, CHRU Tours, Tours, France.

Objective: Joint involvement can be observed during the course of adult IgA vasculitis (IgAV). However, clinical picture, prognosis, or pathophysiological data associated with this condition have been overlooked. We aimed to describe the clinical characteristics and outcome of IgAV patients with joint involvement and look to a specific cytokine profile.

Methods: We analyzed clinical and biological data from a nationwide study that included adult IgAV patients. Presentation and outcomes of patients with or without joint involvement were compared at baseline and during follow-up. Plasma cytokine measurements of IgAV patients included in a prospective study were also analyzed using multiplex assays.

Results: Among 260 patients, 62% had joint involvement. Among them, rheumatological manifestations included arthralgia (100%) or arthritis (16%), mostly involving the knees and ankles. In multivariate analysis, patients with joint involvement, compared to those without, were younger (p = 0.002; OR 0.87; 95% CI 0.80-0.95) and showed more frequent gastrointestinal tract involvement (p = 0.012; OR = 2.08; 95% CI 1.18-3.67). However, no difference in terms of clinical response, relapse, end-stage renal disease, or death was observed between groups. Among 13 cytokines measured, plasma interleukin (IL)-1β level was higher in patients with joint involvement compared to those without (mean ± SEM IL-1β, 3.5 ± 1.2 vs. 0.47 ± 0.1 pg/ml; p = 0.024) or healthy controls (vs. 1.2 ± 0.5 pg/ml; p = 0.076).

Conclusion: Joint involvement is frequent in adult IgAV and is associated with more frequent gastrointestinal involvement. Increased plasma IL-1β levels raise the question of targeting this cytokine in patients with chronic and/or refractory joint involvement. Key Points • Joint involvement in adult IgAV is a frequent manifestation. • Joint involvement is associated with more frequent gastrointestinal manifestations. • Interleukin-1β (IL-1β) might orchestrate joint inflammation in adult IgAV. • IL-1β might be a therapeutic target in patients with chronic and/or refractory joint involvement.
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http://dx.doi.org/10.1007/s10067-021-05937-8DOI Listing
May 2022

Time for precision medicine in systemic sclerosis-associated pulmonary arterial hypertension.

Eur Respir J 2021 06 24;57(6). Epub 2021 Jun 24.

Univ. Lille, U1286 - INFINITE - Institute for Translational Research in Inflammation, Lille, France.

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http://dx.doi.org/10.1183/13993003.00205-2021DOI Listing
June 2021

Acquired Hemophilia A in IgG4-Related Disease: Case Report, Immunopathogenic Study, and Review of the Literature.

Front Immunol 2020 18;11:558811. Epub 2020 Dec 18.

CHU Lille, Département de Médecine Interne et Immunologie Clinique, Lille, France.

We report the observation of a 75-year-old patient referred for cervical lymphadenopathies. A pre-lymphadenectomy blood work revealed an asymptomatic elevation of aPTT with low factor VIII (FVIII) levels and high anti-FVIII antibodies titers, consistent with acquired hemophilia A (AHA). Histological work-up of a cervical lymphadenopathy revealed benign follicular hyperplasia with IgG4 lymphoplasmacytic infiltration; and serum IgG4 levels were markedly elevated, compatible with IgG4-related disease (IgG4-RD). He was successfully treated with a 9-month course of prednisone, secondarily associated with rituximab when an AHA relapse occurred. As this patient presented with an unusual association of rare diseases, we wondered whether there was a link between the two conditions. Our first hypothesis was that the anti-FVIII autoantibodies could be directly produced by the proliferating IgG4 plasma cells as a result of broken tolerance to autologous FVIII. To test this assumption, we determined the anti-FVIII IgG subclasses in our patient and in a control group of 11 AHA patients without IgG4-RD. The FVIII inhibitor was mostly IgG4, with an anti-FVIII IgG4/IgG1 ratio of 42 at diagnosis and 268 at relapse in our patient; similar values were observed in non-IgG4-RD AHA patients. As a second hypothesis, we considered whether the anti-FVIII activity could be the result of a non-specific autoantibody production due to polyclonal IgG4 plasma cell proliferation. To test this hypothesis, we measured the anti-FVIII IgG4/total IgG4 ratio in our patient, as well as in several control groups: 11 AHA patients without IgG4-RD, 8 IgG4-RD patients without AHA, and 11 healthy controls. We found that the median [min-max] ratio was higher in AHA-only controls (2.4 10 [5.7 10-1.79 10]), an oligoclonal setting in which only anti-FVIII plasma cells proliferate, than in IgG4-RD-only controls (3.0 10 [2.0 10-6.0 10]), a polyclonal setting in which all IgG4 plasma cells proliferate equally. Our patient had intermediate ratio values (2.7 10 at diagnosis and 1.0 10 at relapse), which could plead for a combination of both mechanisms. Although no definitive conclusion can be drawn, we hypothesized that the anti-FVIII autoantibody production in our IgG4-RD AHA patient could be the result of both broken tolerance to FVIII and bystander polyclonal IgG4 plasma cell proliferation.
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http://dx.doi.org/10.3389/fimmu.2020.558811DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793697PMC
May 2021

Impact of aging on phenotype and prognosis in IgA vasculitis.

Rheumatology (Oxford) 2021 09;60(9):4245-4251

Université Paris Descartes.

Objectives: Immunoglobulin A vasculitis (IgAV) is a small-vessel vasculitis most frequently benign in children while more severe in adults. We aimed to study the impact of age on presentation and outcome of adult IgAV.

Methods: We conducted a nationwide retrospective study including 260 IgAV patients. Patients were divided into four quartiles according to the age at IgAV diagnosis: <36, 36 ≤ age < 52; 52 ≤ age < 63 and ≥63 years. Comparison of presentation and outcome were performed according to age of disease onset.

Results: Mean age at diagnosis was 50.1 (18) years and 63% were male. IgAV diagnosed in the lowest quartile of age was associated with more frequent joint (P < 0.0001) and gastrointestinal involvement (P = 0.001). In contrast, the oldest patients had more severe purpura with necrotic lesions (P = 0.001) and more frequent renal involvement (P < 0.0001), with more frequent haematuria, renal failure, higher urine protein excretion and more frequent tubulointerstitial lesions. Patients were treated similarly in all groups of age, and clinical response and relapse rates were similar between groups. In the 127 treated patients with follow-up data for >6 months, clinical response and relapse rates were similar between the four groups. Median follow-up was of 17.2 months (9.1-38.3 months). Renal failure at the end of follow-up was significantly more frequent in the highest quartile of age (P = 0.02), but the occurrence of end-stage renal disease was similar in all groups. Last, overall and IgAV-related deaths were associated with increase in age.

Conclusion: Aging negatively impacts the severity and outcome of IgAV in adults. Younger patients have more frequent joint and gastrointestinal involvement, while old patients display more frequent severe purpura and glomerulonephritis.
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http://dx.doi.org/10.1093/rheumatology/keaa921DOI Listing
September 2021

Characteristics of patients with systemic sclerosis suffering from a lower limb amputation: Results of a French collaborative study.

J Scleroderma Relat Disord 2020 Oct 27;5(3):224-230. Epub 2020 Apr 27.

Internal Medicine Department, Hôpital Nord, AP-HM, Marseille, France.

Objective: Systemic sclerosis mainly affects the microvascular network. However, macrovascular manifestations have been reported. We aimed to investigate the characteristics of systemic sclerosis patients with an amputation of a lower limb segment.

Methods: We designed a retrospective, case-control, multicentric study on systemic sclerosis patients with amputation of a lower limb segment secondary to critical ischemia via the French Research Group on Systemic Sclerosis. For each case, a control (systemic sclerosis patient without lower limb symptom) was matched with sex, age (±5 years), and cutaneous subset of systemic sclerosis.

Results: In total, 26 systemic sclerosis patients (mean age of 67.2 ± 10.9 years, 20 females, 21 limited cutaneous forms) with a lower limb amputation and 26 matched controls (mean age of 67.3 ± 11.2 years, 20 females, 22 limited cutaneous forms) were included. At the time of amputation, the mean disease duration was 12.8 (±8.6) years. In comparison to controls, systemic sclerosis patients with amputation had more digital ulcers (p = 0.048), history of digital ulcers (p = 0.026), and a higher prevalence of pulmonary arterial hypertension (p = 0.024). Systemic sclerosis patients with amputation were more often smokers (p = 0.008) and under corticosteroids (p = 0.015). In the multivariate model, pulmonary arterial hypertension, smoking status, and corticosteroids were independent markers associated with lower limb amputation in systemic sclerosis. In the follow-up, 10 patients (38.5%) had recurrent ischemia requiring a new limb amputation, and five patients (19.2%) had an amputation of the contralateral limb.

Conclusion: This study identifies some markers associated with lower limb amputation in systemic sclerosis such as digital ulcers and pulmonary arterial hypertension and points out the high risk associated with tobacco consumption and corticosteroid use.
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http://dx.doi.org/10.1177/2397198320913689DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8922619PMC
October 2020

Low hormone levels during an attack of systemic capillary leak syndrome normalizing after treatment.

Horm Mol Biol Clin Investig 2020 May 20;41(3). Epub 2020 May 20.

Centre Hospitalier Régional Universitaire de Lille, Hôpital Claude Huriez, Service D'Endocrinologie-Diabétologie-Métabolisme, 59037, Lille, France.

We report herein the case of a patient with low blood levels of different hormones during a systemic capillary leak syndrome (Clarkson's disease) attack.
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http://dx.doi.org/10.1515/hmbci-2020-0004DOI Listing
May 2020

Gastrointestinal involvement in adult IgA vasculitis (Henoch-Schönlein purpura): updated picture from a French multicentre and retrospective series of 260 cases.

Rheumatology (Oxford) 2020 Oct;59(10):3050-3057

Department of Internal Medicine.

Objectives: To describe the clinical presentation, treatments and prognosis of gastrointestinal (GI) involvement in adult IgA vasculitis (IgAV).

Methods: Data from 260 adults with IgAV included in a French multicentre retrospective survey were analysed. Presentation and outcomes of patients with (GI+) and without (GI-) GI involvement were compared.

Results: One hundred and thirty-seven (53%) patients had GI involvement. Initial manifestations were abdominal pain in 99%, intestinal bleeding in 31%, diarrhoea in 26% and acute surgical abdomen in only 4%. Abdominal imaging revealed thickening of intestinal wall in 61%, and endoscopies revealed abnormalities in 87%, mostly mucosal ulcerations. GI+ vs GI- patients were younger (46 ± 18 vs 54 ± 18 years; P = 0.0004), had more constitutional symptoms (43% vs 23%; P = 0.0005) and joint involvement (72 vs 50%; P = 0.0002), and higher CRP levels (3.7 vs 1.9 mg/dl; P = 0.001). Clinical response and relapse rates were comparable between groups, and all causes mortality (2 vs 4%) and IgAV-related mortality (1% vs 2%) as well. GI-related deaths were due to intestinal perforation and mesenteric ischaemia.

Conclusion: GI involvement is frequent in adult IgAV. GI involvement is frequent in adult IgAV. Mortality is not uncommon but does not seem to be specifically related to GI. Immunosuppressants should not be preferred as first-line therapy for GI+ patients but may be required in case of acute surgical abdomen.
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http://dx.doi.org/10.1093/rheumatology/keaa104DOI Listing
October 2020

Efficacy of immunosuppressants with bridge vasodilator therapy in severe lupus erythematosus-associated pulmonary arterial hypertension.

ESC Heart Fail 2019 12 19;6(6):1322-1325. Epub 2019 Sep 19.

UFR Médecine, Univ. Lille, F-59000, Lille, France.

Optimal management of systemic lupus erythematosus (SLE)-associated pulmonary arterial hypertension (PAH) remains unclear. Our observation describes the case of a 31-year-old SLE patient presenting with cardiogenic shock revealing severe PAH, in which a therapeutic scheme combining immunosuppressants (pulse cyclophosphamide and corticosteroids) and PAH-specific drugs (bosentan, tadalafil, and epoprostenol) led to a complete normalization of pulmonary haemodynamics and allowed a progressive weaning of PAH vasodilators. This case report supports the efficacy of immunosuppressants and use of PAH-specific therapy as a bridge therapy in severe SLE-PAH. Further studies on larger population are required to confirm these findings.
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http://dx.doi.org/10.1002/ehf2.12507DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6989275PMC
December 2019

Factors associated with the 6-minute walk distance in patients with systemic sclerosis.

Arthritis Res Ther 2017 Dec 15;19(1):279. Epub 2017 Dec 15.

University of Lille, INSERM U995, LIRIC-Lille Inflammation Research International Center, F-59000, Lille, France.

Background: There is an ongoing debate regarding the relevance of the 6-minute walking distance (6MWD) in systemic sclerosis (SSc) assessment, widely used as a usual test in these patients as well as an outcome measure in clinical trials. In this work, we aimed to assess the associations between the 6MWD and various disease parameters in patients with SSc.

Methods: Consecutive patients followed in our SSc National Reference Centre were included in this cross-sectional study if they fulfilled the 2013 American College of Rheumatology/European League Against Rheumatism criteria for SSc. Data were systematically collected during a comprehensive standardized evaluation that included a 6-minute walk test, clinical assessment, biological results, pulmonary function tests, transthoracic echocardiography, composite scores (European Scleroderma Study Group Activity Index, Medsger severity score, Health Assessment Questionnaire-Disability Index (HAQ-DI)) and treatments. Associations of the 6MWD with various disease parameters were assessed by linear regression in univariate and multivariate analyses.

Results: The study population comprised 298 patients (females 81%; mean age 58.2 ± 13.3 years; limited cutaneous SSc 82%; interstitial lung disease (ILD) 42%; pulmonary arterial hypertension (PAH) 6%). The 6MWD was significantly and independently associated with gender, age, body mass index, baseline heart rate (HR), HR variation during the test, PAH, history of arterial thrombosis and C-reactive protein levels, as well as with the HAQ-DI score in a sensitivity analysis. Muscle involvement, joint involvement and ILD were not independently associated with the 6MWD.

Conclusions: During SSc, the 6MWD is independently associated with initial HR and HR variation; with PAH but not ILD, suggesting that pulmonary vasculopathy may have a greater impact than parenchymal involvement on functional limitation; and with global markers of disease activity and patient disability. These results give clinicians further insight into how to interpret the 6MWD in the context of SSc.
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http://dx.doi.org/10.1186/s13075-017-1489-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5732461PMC
December 2017

Characteristics and Management of IgA Vasculitis (Henoch-Schönlein) in Adults: Data From 260 Patients Included in a French Multicenter Retrospective Survey.

Arthritis Rheumatol 2017 09;69(9):1862-1870

Department of Internal Medicine, Hôpital de Bondy, AP-HP, Paris, France.

Objective: Data on adult IgA vasculitis (Henoch-Schönlein) (IgAV) are scarce. This survey was designed to better define the clinical spectrum of IgAV and efficacy of treatments in a French patient population.

Methods: Data on clinical characteristics, histologic features, and treatment response from 260 patients with IgAV included in a French multicenter retrospective survey were analyzed. Efficacy data were compared using different statistical models.

Results: The mean ± SD age of the patients with IgAV at diagnosis was 50.1 ± 18 years, and 63% of patients were male. Baseline manifestations included purpura (100%), arthralgias/arthritis/myalgia (61%), glomerulonephritis (70%), and/or gastrointestinal involvement (53%). Thirty percent of patients showed renal failure at baseline. In univariate analysis, the response to therapy was 80% (64 of 80) in patients treated with corticosteroids (CS) alone, compared to 77% (23 of 30) in patients treated with CS plus cyclophosphamide (CYC) and 59% (10 of 17) in patients treated with colchicine (P = 0.17). Multivariable analysis showed that treatment with CS or CS plus CYC was more effective than colchicine in achieving a response. Efficacy differences were demonstrated using different statistical models: in the multivariable logistic regression model, odds ratio (OR) 3.68, 95% confidence interval (95% CI) 1.10-12.33 (P = 0.03); in the inverse probability weighting on propensity score model, OR 3.75, 95% CI 1.28-10.99 (P = 0.02). The efficacy of CS plus CYC as compared to CS alone was discordant according to the analytic method used. Analysis with the multivariable logistic regression model did not demonstrate a difference between CS plus CYC and CS alone (OR 0.88, 95% CI 0.29-2.67; P = 0.82). In contrast, inverse probability weighting on propensity score showed that CS plus CYC was more effective than CS alone (OR 1.79, 95% CI 1.00-3.20; P = 0.049).

Conclusion: This series constitutes the largest series of adults with IgAV reported in the literature so far. It provides data on clinical and histologic presentation and therapeutic efficacy, suggesting that CS alone appears to be a reasonable first-line therapy in patients with IgAV, while the benefit of adding CYC to CS remains uncertain.
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http://dx.doi.org/10.1002/art.40178DOI Listing
September 2017

Intravenous immunoglobulins in systemic sclerosis: Data from a French nationwide cohort of 46 patients and review of the literature.

Autoimmun Rev 2017 Apr 13;16(4):377-384. Epub 2017 Feb 13.

Univ. Lille, INSERM U995 - LIRIC - Lille Inflammation Research International Center, F-59000 Lille, France; INSERM, U995, F-59000 Lille, France; CHU Lille, Département de Médecine Interne et Immunologie Clinique, F-59000 Lille, France; Centre National de Référence Maladies Systémiques et Auto-immunes Rares (Sclérodermie Systémique), F-59000 Lille, France; Health Care Provider of the European Reference Network on Rare Connective Tissue and Musculoskeletal Diseases Network (ReCONNET). Electronic address:

Background: As intravenous immunoglobulins (IVIG) exhibit immunomodulatory and antifibrotic properties, they may be a relevant treatment for systemic sclerosis (SSc). The objectives of this work were thus to report on the efficacy and safety of IVIG in a population of SSc patients and to review the available literature.

Methods: 46 patients from 19 French centers were retrospectively recruited. They were included if they had a diagnosis of SSc and received at least 1 IVIG infusion at a dosage >1g/kg/cycle. Relevant data collected at IVIG discontinuation were compared to those collected at IVIG initiation. A comprehensive literature review was performed.

Results: We observed a significant improvement of muscle pain (74% vs. 20%, p<0.0001), muscle weakness (45% vs. 21%, p=0.01), joint pain (44% vs. 19%, p=0.02), CK levels (1069±1552UI vs. 288±449UI, p<0.0001) and CRP levels (13.1±17.6mg/L vs. 9.2±16.6mg/L, p=0.001). We also noted a trend for an improvement of gastro-esophageal reflux disease (68% vs. 53%, p=0.06) and bowel symptoms (42% vs. 27%, p=0.06). Skin and cardiorespiratory involvements remained stable. Finally, corticosteroid daily dose was significantly lower by the end of treatment (13.0±11.6mg/day vs. 8.9±10.4mg/day, p=0.01). Only two severe adverse events were reported (one case of deep vein thrombosis and one case of diffuse edematous syndrome).

Conclusion: Our work suggests that IVIG are a safe therapeutic option that may be effective in improving musculoskeletal involvement, systemic inflammation, digestive tract symptoms and could be corticosteroid sparing.
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http://dx.doi.org/10.1016/j.autrev.2017.02.008DOI Listing
April 2017

B Cell Homeostasis and Functional Properties Are Altered in an Hypochlorous Acid-Induced Murine Model of Systemic Sclerosis.

Front Immunol 2017 7;8:53. Epub 2017 Feb 7.

U995, LIRIC - Lille Inflammation Research International Center, Université de Lille, Lille, France; INSERM, U995, Lille, France; Département de Médecine Interne et Immunologie Clinique, CHU Lille, Lille, France; Centre National de Référence Maladies Systémiques et Auto-immunes Rares (Sclérodermie Systémique), Lille, France.

Introduction: During systemic sclerosis (SSc), peripheral B cells display alterations in subset homeostasis and functional properties and are a promising therapeutic target. However, there is only few data regarding whether these anomalies are accurately reproduced in animal models of SSc.

Objective: In this work, we assessed the B cell homeostasis modifications in an experimental model of SSc [hypochlorous acid (HOCl)-induced mouse], both at a phenotypic and functional level, during the course of the disease.

Methods: Balb/c mice underwent daily intradermal injections of HOCl (or phosphate-buffered saline) and were then sacrificed at day 21 (early inflammatory stage) or day 42 (late fibrotic stage). For phenotypic studies, the distribution of the main spleen cell subsets (B cells, T CD4 and CD8 cells, NK cells, macrophages) and splenic B cell subsets (immature, mature naïve, germinal center, antibody-secreting, memory, B1) was assessed by flow cytometry. For functional studies, splenic B cells were immediately MACS-sorted. Production of interleukin (IL)-6, CCL3, IL-10, and transforming growth factor (TGF)-β was assessed by RT-PCR and after 48 h of culture by ELISA. Regulatory B cell (Breg) counts were quantified by flow cytometry.

Results: Phenotypic analyses showed an early expansion of transitional B cells, followed by a late expansion of the mature naive subset and decrease in plasmablasts and memory B cells. These anomalies are similar to those encountered in SSc patients. Functional analyses revealed a B-cell overproduction of pro-inflammatory cytokines (IL-6 and CCL3) and an impairment of their anti-inflammatory capacities (decreased production of IL-10 and TGF-β, reduced levels of Bregs) at the early inflammatory stage; and an overproduction of pro-fibrotic cytokines (TGF-β and IL-6) at the late fibrotic stage. These results approximate the anomalies observed in human SSc.

Conclusion: This work reports the existence of anomalies in B cell homeostasis and functional properties in an animal model of SSc that approximate those displayed by SSc patients. These anomalies vary over the course of the disease, which pleads for their participation in inflammatory and fibrotic events. This makes the HOCl mouse a relevant experimental model for the study of B cells, and therefore, B-cell-targeted therapies in SSc.
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http://dx.doi.org/10.3389/fimmu.2017.00053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5293837PMC
February 2017

Pulmonary arterial hypertension in idiopathic inflammatory myopathies: Data from the French pulmonary hypertension registry and review of the literature.

Medicine (Baltimore) 2016 Sep;95(39):e4911

aUniversity of Lille, INSERM U995, LIRIC, Lille Inflammation Research International Center bCHU Lille, Département de Médecine Interne et Immunologie Clinique cCentre National de Référence Maladies Systémiques et Auto-immunes Rares (Sclérodermie Systémique), Lille dUniversity Paris-Sud, Faculté de Médecine, Université Paris-Saclay eAP-HP, Service de Pneumologie, DHU Thorax Innovation, Hôpital Bicêtre, Le Kremlin-Bicêtre fINSERM UMR_S999, LabEx LERMIT, Centre Chirurgical Marie-Lannelongue, Le Plessis-Robinson gDépartement de Médecine Interne et Immunologie Clinique, Centre National de Référence Maladies Neuromusculaires, Hôpital La Pitié-Salpêtrière, AP-HP, INSERM U974, Université Paris VI Pierre et Marie Curie, Paris hClinique Universitaire de Pneumologie, Centre Hospitalier Universitaire, Grenoble, France iUniversité Joseph Fourier, Grenoble jService de médecine interne et rhumatologie 3C/5D, Centre Hospitalier Universitaire Pierre Zobda-Quitman kDépartement de Cardiologie, Centre Hospitalier Universitaire Pierre Zobda-Quitman, Fort-de-France, Martinique lHospices Civils de Lyon, Service de Pneumologie, Centre de Compétence de l'Hypertension Pulmonaire, Centre de Référence des Maladies Pulmonaires Rares, Lyon mService de Médecine Interne, Centre de Référence des Vascularites Nécrosantes et de la Sclérodermie Systémique, Université Paris Descartes, Hôpital Cochin, Paris, France.

Occurrence of pulmonary arterial hypertension (PAH) in idiopathic inflammatory myopathies (IIMs) without extensive interstitial lung disease (ILD) has rarely been described in the medical literature. This study aimed to report all cases with association of PAH and IIM in the French Pulmonary Hypertension (PH) Registry, to identify IIM features associated with the presence of PAH, and to describe treatment modalities of these patients.All cases of IIM-PAH were retrieved from the French PH Registry, which gathers PH patients prospectively enrolled by 27 referral hospital centers across France. Patients were excluded if they had an extensive ILD or overlap syndrome. Characteristics of IIM-PAH patients were compared with a control group of IIM patients without PH.Among the 5223 PH patients in the Registry, 34 had a diagnosis of IIM. Among them, 3 IIM-PAH patients (2 females and 1 male) had no evidence of extensive ILD or overlap syndrome, and were included in this study. In these 3 patients, dermatomyositis (DM) was the only identified IIM. One patient had autoantibodies classically associated with IIM (anti-Ku). PAH had always developed after IIM onset, was severe in all cases, and led to a marked functional impairment.By pooling our cases with 6 patients previously reported in the literature, and comparing them with a control cohort of 35 IIM patients without PH, we identify several IIM characteristics possibly associated with PAH occurrence, including DM subtype (78% vs 46%; P = 0.02), skin involvement (P = 0.04), anti-SSA antibodies (P = 0.05), and peripheral microangiopathy (P = 0.06).Overall, IIM-PAH patients were managed by corticosteroids and/or immunosuppressants, either alone or combined with PAH therapy. Patients did not seem to respond to IIM treatment alone.Our study reports for the first time the rare but possible association of PAH and IIM in a large prospective PH Registry. In that setting, PAH seems associated with DM, skin involvement, peripheral microangiopathy, and anti-SSA positivity. The best therapeutic strategy for IIM-PAH remains to be defined.
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http://dx.doi.org/10.1097/MD.0000000000004911DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5265921PMC
September 2016

Giant cell arteritis and ulcerative colitis: An unusual association.

Semin Arthritis Rheum 2016 08 16;46(1):e3-5. Epub 2016 Mar 16.

Service de Médecine Interne, Néphrologie et Médecine Vasculaire, Centre Hospitalier de Valenciennes, Avenue Désandrouins, 59300 Valenciennes, France.

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http://dx.doi.org/10.1016/j.semarthrit.2016.03.008DOI Listing
August 2016

A prospective study of the 6 min walk test as a surrogate marker for haemodynamics in two independent cohorts of treatment-naïve systemic sclerosis-associated pulmonary arterial hypertension.

Ann Rheum Dis 2016 Aug 31;75(8):1457-65. Epub 2015 Aug 31.

Faculté de Médecine, Université Paris-Sud, Le Kremlin-Bicêtre, France AP-HP, Service de Pneumologie, DHU Thorax Innovation, Hôpital Bicêtre, Le Kremlin-Bicêtre, France INSERM U999, Centre Chirurgical Marie-Lannelongue, LabEx LERMIT, Le Plessis-Robinson, France.

Objectives: Despite the wide use of the 6 min walk distance (6MWD), no study has ever assessed its validity as a surrogate marker for haemodynamics and predictor of outcome in isolated pulmonary arterial hypertension associated with systemic sclerosis (SSc-PAH). We designed this work to address this issue.

Methods: Treatment-naïve patients with SSc-PAH were prospectively included from two sources: the French PAH Network (a prospective epidemiological cohort) (n=83) and randomised clinical trials submitted for drug approval (Food and Drug Administration) (n=332). Correlations between absolute values of the 6MWD and haemodynamics at baseline, as well as between variations of 6MWD and haemodynamics during follow-up, were studied in both populations.

Results: In the French cohort, baseline cardiac output (CO) (R(2)=0.19, p=0.001) and New York Heart Association class (R(2)=0.10, p<0.001) were significantly and independently correlated with baseline 6MWD in multivariate analysis. A significant, independent, but weaker, correlation with CO was also found in the Food and Drug Administration sample (R(2)=0.04, p<0.001). During follow-up, there was no association between the changes in 6MWD and haemodynamic parameters in patients under PAH-specific treatments.

Conclusions: In SSc-PAH, CO independently correlates with 6MWD at baseline, but accounts for a small amount of the variance of 6MWD in both study samples. This suggests that other non-haemodynamic factors could have an impact on the walk distance. Moreover, variations of 6MWD do not reflect changes in haemodynamics among treated patients. Our results suggest that 6MWD is not an accurate surrogate marker for haemodynamic severity, nor an appropriate outcome measure to assess changes in haemodynamics during follow-up in treated SSc-PAH.
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http://dx.doi.org/10.1136/annrheumdis-2015-207336DOI Listing
August 2016

Serum free light chains of immunoglobulins as biomarkers for systemic sclerosis characteristics, activity and severity.

Autoimmun Rev 2014 Sep 25;13(9):974-80. Epub 2014 Jul 25.

Université Lille Nord de France, Lille, France; EA2686, IMPRT IFR 114, Faculté de Médecine, Lille, France; Institut d'Immunologie, Centre de Biologie-Pathologie-Génétique, CHRU Lille, Lille, France.

Systemic sclerosis (SSc) is a chronic autoimmune connective tissue disease. Humoral immunity and B cells are thought to play an important role in the pathophysiology of the disease. B cells are activated, produce specific autoantibodies and profibrotic cytokines. One way to assess B cell activation is to measure serum free light chains of immunoglobulins (sFLC) levels. We assess here sFLC levels in patients with systemic sclerosis (SSc) and their correlation with the disease characteristics, activity and severity. One hundred and thirty-four SSc patients were prospectively enrolled and compared to 401 age- and sex-matched healthy controls. sFLC levels were measured by a new quantitative immunoassay. sFLC levels were significantly higher in SSc patients than in healthy controls. sFLC levels correlated with modified Rodnan skin score and were independently associated with the presence of interstitial lung disease and its severity. In univariate analysis, sFLC levels correlated with SSc activity, as measured by the European Scleroderma Study Group activity index, and severity, as measured by the Medsger's total severity score. In multivariate analysis, beta2-microglobulin levels correlated with disease activity, BAFF levels with severity and sFLC with neither of these. Other B-cell activation biomarkers (IgG, IgA, beta2-microglobulin and BAFF) were independently correlated with sFLC. sFLC levels are elevated in SSc and are independently associated with lung disease and its severity. B-cell activation biomarkers, including sFLC, beta2-microglobulin and BAFF, correlate with disease severity and activity. These results further support the role of B cell activation in the pathophysiology of SSc.
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http://dx.doi.org/10.1016/j.autrev.2014.07.003DOI Listing
September 2014

Thrombosis of the left subclavian vein complicating SAPHO syndrome: a case report.

Joint Bone Spine 2014 Oct 2;81(5):460-1. Epub 2014 Apr 2.

Department of Rheumatology, Saint-Philibert Hospital, 115, rue du Grand-But, 59160 Lomme, France.

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http://dx.doi.org/10.1016/j.jbspin.2014.02.002DOI Listing
October 2014

Bilateral femoral periostitis revealing polyarteritis nodosa.

BMJ Case Rep 2013 Nov 22;2013. Epub 2013 Nov 22.

Department of Internal Medicine, National Centre for Rare Auto-Immune and Systemic Diseases, Claude-Huriez Hospital, Regional University Hospital of Lille, Lille-Nord-de-France University, Lille, France.

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http://dx.doi.org/10.1136/bcr-2013-200695DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3842004PMC
November 2013
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