Studies have suggested involvement of interleukin 17 (IL-17) in autoimmune diseases, although its effect on B cell biology has not been clearly established. Here we demonstrate that IL-17 alone or in combination with B cell-activating factor controlled the survival and proliferation of human B cells and their differentiation into immunoglobulin-secreting cells. This effect was mediated mainly through the nuclear factor-kappaB-regulated transcription factor Twist-1. In support of the relevance of our observations and the potential involvement of IL-17 in B cell biology, we found that the serum of patients with systemic lupus erythematosus had higher concentrations of IL-17 than did the serum of healthy people and that IL-17 abundance correlated with the disease severity of systemic lupus erythematosus.

SRC remains associated with severe morbidity and mortality. CS might increase the risk of developing SRC. Further studies are needed to confirm these results.

Background and objectives: Standard treatment for lupus nephritis, including corticosteroids and cyclophosphamide, is efficient but is still associated with refractory or relapsing disease, or severe deleterious effects. Rituximab, a monoclonal chimeric anti-B cell antibody, is increasingly used in patients with lupus nephritis, but reported series were small and had a short follow-up.Design, setting, participants, & measurements: The authors analyzed clinical and histologic data of 20 patients who were treated with rituximab for lupus nephritis and followed up for at least 12 mo.Results: Nineteen women and one man received rituximab as induction treatment for an active class IV (15 cases) or class V (5 cases) lupus nephritis. Rituximab was given for lupus nephritis refractory to standard treatment (12 cases), for relapsing disease (6 cases), or as first-line treatment (2 cases). Three patients received cyclophosphamide concomitantly with rituximab. Ten received new injections of rituximab as maintenance therapy. Side effects included mainly five infections and four moderate neutropenias. After a median follow-up of 22 mo, complete or partial renal remission was obtained in 12 patients (60%). Lupus nephritis relapsed in one patient, who responded to a new course of rituximab. The achievement of B cell depletion 1 mo after rituximab, which negatively correlated with black ethnicity and hypoalbuminemia, was strongly associated with renal response. Rapidly progressive glomerulonephritis did not respond to rituximab. Conclusion: Rituximab is an interesting therapeutic option in relapsing or refractory lupus nephritis when early B cell depletion is obtained.

Clinical difficulties in predicting systemic lupus erythematosus (SLE) renal flares are still encountered. Biological markers such as autoantibodies (aAbs) may be of major interest for clinicians in the follow-up of SLE patients. The aim of our study was to investigate the clinical utility of one of these biological markers, anti-C1q aAbs, in predicting renal flares of SLE nephritis in comparison with the 'gold standard' anti-double stranded DNA (anti-dsDNA) aAbs. Anti-C1q aAbs and anti-dsDNA aAbs were analysed through a longitudinal retrospective study of 23 SLE patients presenting with one or more renal flares. Anti-C1q and/or anti-dsDNA aAbs were found in 20 (87%) of 23 patients, of whom 16 (69%) displayed both. Thirty-three renal flares occurred during the course of the study, and anti-C1q aAbs and anti-dsDNA aAbs were positive in 25 (76%) and 24 (73%) of these flares respectively. The sensitivity of anti-C1q and/or anti-dsDNA aAbs in predicting renal flares reached 85%. The specificity of anti-C1q aAbs was 84%, of anti-dsDNA aAbs 77% and of both aAbs 97%. Positive and negative predictive values were as follows: 56% and 70% for anti-C1q aAbs, 53% and 72% for anti-dsDNA aAbs. The combination of both aAbs had the highest positive predictive value (69%), whereas absence of both aAbs was associated with the highest negative predictive value (74%). In conclusion, our results confirm that anti-C1q aAbs are present in a significant percentage of SLE patients with active renal involvement, suggesting that these aAbs could be a useful additional marker. The presence of anti-C1q and anti-dsDNA aAbs was associated with a high risk of renal flare, whereas the absence of both aAbs excluded such an event. These data confirm that systematic detection of anti-C1q and anti-dsDNA aAbs is of interest for the follow-up in SLE patients with renal involvement.

Eighty-two consecutive Caucasian adults (52 males, 30 females, aged 17-86 years) with membranous glomerulonephritis were prospectively evaluated for possible aetiological factors 1-4 weeks after renal biopsy. Presumed causes were identified in 17 patients (21%) as follows: drugs in five (D-penicillamine 3, captopril 1, fenoprofen 1); malignancy in four; chronic thyroiditis in three; systemic lupus erythematosus (SLE) in two; secondary syphilis in one; hepatitis B virus (HBV) infection in one and non-insulin-dependent diabetes mellitus in one patient. Except for age (patients with secondary membranous glomerulonephritis were older), clinical presentation and histological stage distribution did not differ between the secondary and the primary groups. Ten out of the 17 patients with secondary membranous glomerulonephritis (59%) achieved complete clinical remission within 12 months. The incidence of associated conditions in adults with membranous glomerulonephritis in this study corresponds with that reported in the few previous series. Although membranous glomerulonephritis is deemed to be idiopathic in most cases, it seems warranted to search for medication, malignancy, SLE, HBV infection, syphilis and thyroiditis as possible aetiological factors. Further evaluation should be orientated by the clinical context. An improved outcome of membranous glomerulonephritis may be expected insofar as the underlying condition is controlled.

The aim of this study was to describe the clinical and biological features of Mevalonate kinase deficiency (MKD) in patients diagnosed in adulthood.This is a French and Belgian observational retrospective study from 2000 to 2014. To constitute the cohort, we cross-check the genetic and biochemical databases. The clinical, enzymatic, and genetic data were gathered from medical records.Twenty-three patients were analyzed. The mean age at diagnosis was 40 years, with a mean age at onset of symptoms of 3 years. All symptomatic patients had fever. Febrile attacks were mostly associated with arthralgia (90.9%); lymphadenopathy, abdominal pain, and skin lesions (86.4%); pharyngitis (63.6%); cough (59.1%); diarrhea, and hepatosplenomegaly (50.0%). Seven patients had psychiatric symptoms (31.8%). One patient developed recurrent seizures. Three patients experienced renal involvement (13.6%). Two patients had angiomyolipoma (9.1%). All but one tested patients had elevated serum immunoglobulin (Ig) D level. Twenty-one patients had genetic diagnosis; most of them were compound heterozygote (76.2%). p.Val377Ile was the most prevalent mutation. Structural articular damages and systemic AA amyloidosis were the 2 most serious complications. More than 65% of patients displayed decrease in severity and frequency of attacks with increasing age, but only 35% achieved remission.MKD diagnosed in adulthood shared clinical and genetic features with classical pediatric disease. An elevated IgD concentration is a good marker for MKD in adults. Despite a decrease of severity and frequency of attacks with age, only one-third of patients achieved spontaneous remission.

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Background. Chronic kidney disease (CKD) and endstage renal failure (ESRF) are major complications after a heart transplant. The aim of this study is to compare survival in heart transplant (HT) vs non-heart transplant (non-HT) patients starting dialysis. Methods. Survival was studied among the 539 newly dialysed patients between 1 January 1995 and 31 December 2005 in our Department. All patients were prospectively followed from the date of first dialysis up to death or 31 December 2005. Multivariate survival analysis adjusted on baseline characteristics was performed with the Cox model. Results. There were 21 HT patients and they were younger than non-HT patients at first dialysis: 58.6 AE 11.6 vs 63.0 AE 16.2 years (P ¼ 0.09). Calcineurin inhibitor nephrotoxicity was the main cause of ESRF in HT patients (47.6%). Crude 1, 3 and 5-year survival rates in HT and in non-HT patients were as follows: 76.2%, 57.1%, 28.6% and 79.1%, 58.7%, 46.7% (P ¼ 0.2). The adjusted hazard ratio of death in HT vs non-HT patients was 2.27 [1.33-3.87], P ¼ 0.003. Sudden death was the main cause of death in HT patients, in 33.3% vs 10.4% in non-HT patients (P ¼ 0.01). Five HT patients benefited from renal transplant. They were all alive at the end of the study period, while one patient among the 16 remaining on dialysis survived. Conclusion. HT patients with CKD who reached ESRF have a poor outcome after starting dialysis in comparison with other ESRF patients. Improvement in renal function management in the case of CKD is needed in these patients and non-nephrotoxic immunosuppressive regimens have to be evaluated. Renal transplant should be the ESRF treatment of choice in HT patients.