Vitamine D et Lupus Erythémateux Systémique (Statut vitaminique D dans une cohorte française multicentrique, et relation entre la concentration sérique de 25-hydroxyvitamine D et l' activité de la maladie)

Les objectifs de ce travail étaient d'évaluer le statut vitaminique D dans une cohorte française multicentrique de patients lupiques, et d'étudier la relation entre le taux sérique de 25-hydroxyvitamine D [25(OH)D] et les paramètres clinico-biologiques du lupus érythémateux systémique (LES) dont l'activité de la maladie. La 25(OH)D a été dosée chez 150 patients lupiques randomisés dans le cadre d'un essai thérapeutique prospectif. La relation entre le taux de 25(OH)D et le SLEDAI (Systemic Lupus Erythematosus Disease" Activity Index) et les autres paramètres a été étudiée grâce à un modèle de régression linéaire multiple. L'âge et la durée d'évolution moyens étaient de 39,4 +- 10,7 et 11,2 +- 8,1 ans respectivement. Un syndrome des antiphospholipides (SAPL) était défini chez 18,7 % des patients. Le SLEDAI moyen était de 1.8 +- 2,5. Le taux moyen de 25(OH)D était de 20,6 +- 9,8 ng/mL, 67,3 % des patients présentant une insuffisance et 15,4 % une carence en vitamine D. En analyse multivariée, les facteurs indépendamment associés à un taux de 25(OH)D plus bas étaient un âge plus jeune (p = 0,016), un indice de masse corporelle plus élevé (p = 0,007), l'existence d'une photosensibilité (p = 0,034), l'absence de SAPL défini (p = 0,0004), et un SLEDAI plus élevé (p = 0,036). Une large majorité des patients présente un statut vitaminique D suboptimal, et nous trouvons une corrélation inverse entre le taux de 25(OH)D et le SLEDAI. Ces résultats posent la question d'une possible réduction du risque de poussée de LES en cas d'obtention et de maintien durable d'un statut vitaminique D optimal grâce à une supplémentation adaptée.PARIS6-Bibl.Pitié-Salpêtrie (751132101) / SudocSudocFranceF

Intravenous immunoglobulin-induced IL-33 is insufficient to mediate basophil expansion in autoimmune patients

International audienceIntravenous immunoglobulin (IVIg) is used in the therapy of various autoimmune and inflammatory diseases. Recent studies in experimental models propose that anti-inflammatory effects of IVIg are mainly mediated by a2,6-sialylated Fc fragments. These reports further suggest that a2,6-sialylated Fc fragments interact with DC-SIGN 1 cells to release IL-33 that subsequently expands IL-4-producing basophils. However, translational insights on these observations are lacking. Here we show that IVIg therapy in rheumatic patients leads to significant raise in plasma IL-33. However, IL-33 was not contributed by human DC-SIGN 1 dendritic cells and splenocytes. As IL-33 has been shown to expand basophils, we analyzed the proportion of circulating basophils in these patients following IVIg therapy. In contrast to mice data, IVIg therapy led to basophil expansion only in two patients who also showed increased plasma levels of IL-33. Importantly, the fold-changes in IL-33 and basophils were not correlated and we could hardly detect IL-4 in the plasma following IVIg therapy. Thus, our results indicate that IVIg-induced IL-33 is insufficient to mediate basophil expansion in autoimmune patients. Hence, IL-33 and basophil-mediated anti-inflammatory mechanism proposed for IVIg might not be pertinent in humans

Restoration of regulatory and effector T cell balance and B cell homeostasis in systemic lupus erythematosus patients through vitamin D supplementation.

International audienceABSTRACT: INTRODUCTION: Systemic lupus erythematosus (SLE) is a T and B cell-dependent autoimmune disease characterized by the appearance of autoantibodies, a global regulatory T cells (Tregs) depletion and an increase in Th17 cells. Recent studies have shown the multifaceted immunomodulatory effects of vitamin D, notably the expansion of Tregs and the decrease of Th1 and Th17 cells. A significant correlation between higher disease activity and lower serum 25-hydroxyvitamin D levels [25(OH)D] was also shown. METHODS: In this prospective study, we evaluated the safety and the immunological effects of vitamin D supplementation (100 000 IU of cholecalciferol per week for 4 weeks, followed by 100 000 IU of cholecalciferol per month for 6 months.) in 20 SLE patients with hypovitaminosis D. RESULTS: Serum 25(OH)D levels dramatically increased under vitamin D supplementation from 18.7±6.7 at day 0 to 51.4±14.1 (p<0.001) at 2 months and 41.5±10.1 ng/mL (p<0.001) at 6 months. Vitamin D was well tolerated and induced a preferential increase of naïve CD4+ T cells, an increase of regulatory T cells and a decrease of effector Th1 and Th17 cells. Vitamin D also induced a decrease of memory B cells and anti-DNA antibodies. No modification of the prednisone dosage or initiation of new immunosuppressant agents was needed in all patients. We did not observe SLE flare during the 6 months follow-up period. CONCLUSIONS: This preliminary study suggests the beneficial role of vitamin D in SLE patients and needs to be confirmed in randomized controlled trials

Anti-RNP antibodies delineate a subgroup of necrotizing myositis

International audienc

Autoimmune and inflammatory diseases associated with chronic myelomonocytic leukemia: A series of 26 cases and literature review

International audienceWe wanted to describe the characteristics, treatment and outcome of autoimmune and inflammatory diseases (SAIDs) associated with chronic myelomonocytic leukemia (CMML), and conducted a French multicenter retrospective study and a literature review. We included 26 cases of CMML (median age 75 years, 54% female), 80% with CMML-1. CPSS score was low (0 or 1) in 75% of cases. SAIDS was systemic vasculitis in 54%. Diagnosis of the 2 diseases was concomitant in 31% cases, and CMML was diagnosed before SAIDs in 12 cases (46%). First line treatment for SAIDs consisted mostly of steroid, with 85% of response. Second-line treatment was needed in 40% cases. Six patients received hypomethylating agents, with 66% response on SAIDs. A literature review found 49 cases of CMML-associated SAIDs, in whom SAIDs was systemic vasculitis in 29% cases.Hence, vasculitis is the most frequent SAIDs associated with CMML. After initial response to steroids, recurrence and steroid-dependence were frequent. Hypomethylating agents may be interesting in this context. © 2016 Elsevier Ltd

High risk of cancer in autoimmune necrotizing myopathies: usefulness of myositis specific antibody

IF 10.103International audienceCancer occurs frequently in dermatomyositis and is a major cause of mortality. Yves Allenbach et al. report that patients with necrotising auto-immune myopathies also have an increased risk of malignancy, and that myositis-specific antibodies can be used to identify those at greatest risk.Cancer occurs frequently in dermatomyositis and is a major cause of mortality. Yves Allenbach et al. report that patients with necrotising auto-immune myopathies also have an increased risk of malignancy, and that myositis-specific antibodies can be used to identify those at greatest risk.Cancer can occur in patients with inflammatory myopathies. This association is mainly observed in dermatomyositis, and myositis-specific antibodies have allowed us to delineate patients at an increased risk. Malignancy is also reported in patients with necrotizing autoimmune myopathies, but the risk remains elusive. Anti-signal recognition particle or anti-HMGCR antibodies have been specifically associated with necrotizing autoimmune myopathies. We aimed at screening the incidence of cancer in necrotizing autoimmune myopathies. A group of patients (n = 115) with necrotizing autoimmune myopathies with or without myositis-specific antibodies was analysed. Malignancy occurred more frequently in seronegative necrotizing autoimmune myopathies patients and in HMGCR-positive patients compared to anti-signal recognition particle positive patients. Synchronous malignancy was diagnosed in 21.4% and 11.5% of cases, respectively, and incidence of cancer was higher compared to the general population in both groups. No specific type of cancer was predominant. Patients suffering from a synchronous cancer had a decreased median survival time. Cancer screening is necessary in seronegative necrotizing autoimmune myopathies and in HMGCR-positive patients but not in anti-signal recognition particle-positive patients

Clinicopathologic characteristics, treatment, and outcomes of tubulointerstitial nephritis and uveitis syndrome in adults: A national retrospective strobe-compliant study

International audienceTubulointerstitial nephritis and uveitis (TINU) syndrome is a rare disease, defined by the association of idiopathic acute TINU. The aim of our work was to determine the characteristics of adult TINU syndrome in France, and to assess factors (including treatment) influencing medium-term prognosis.We conducted a nationwide study including 20 French hospitals. Clinical, laboratory, and renal histopathologic data of 41 biopsy-proven TINU syndromes were retrospectively collected. The patients were diagnosed between January 1, 1999 and December 1, 2015.Twenty-five females and 16 males were included (F/M ratio: 1.6:1). The median age at disease onset was 46.8 years (range 16.8-77.4) with a median serum creatinine level at 207 μmol/L (range 100-1687) and a median estimated glomerular filtration rate (eGFR) at 27 mL/min per 1.73 m (range 2-73). Twenty-nine patients (71%) had a bilateral anterior uveitis and 24 (59%) had deterioration in general health at presentation. Moderate proteinuria was found in 32 patients (78%) (median proteinuria 0.52 g/24 h; range 0.10-2.10), aseptic leukocyturia in 25/36 patients (70%). The evaluation of renal biopsies revealed 41 patients (100%) with an acute tubulointerstitial nephritis, 19/39 patients (49%) with light to moderate fibrosis and 5 patients (12%) with an acute tubular necrosis. Thirty-six patients (88%) were treated with oral corticosteroids. After 1 year of follow-up, the median eGFR was 76 mL/min per 1.73 m (range 17-119) and 32% of the patients suffered from moderate to severe chronic kidney disease. Serum creatinine (P < 0.001, r = -0.54), serum bicarbonate and phosphate levels (respectively, P = 0.01, r = 0.53; and P = 0.04, r = 0.46), and age (P = 0.03, r = -0.37) at the 1st symptoms were associated with eGFR after 1 year. During the 1st year 40% of patients had uveitis relapses. The use of oral corticosteroids was not associated with a better kidney function but was associated with fewer uveitis relapses (P = 0.44 and 0.02, respectively).In our study, 32% of patients were suffering from moderate to severe chronic kidney disease after 1 year of follow-up, and 40% had uveitis relapses during this follow-up. This work also suggests that oral corticosteroids are effective for the treatment of TINU syndrome's uveitis

Tocilizumab for Severe Worsening COVID-19 Pneumonia: a Propensity Score Analysis

International audienc