Glomerulosclerosis clinical trials

Cellules B et Microbiote Dans le SNI

Idiopathic nephrotic syndrome (INS) is a clinical entity defined by the association of selective albuminuria resulting in hypoalbuminemia, and nonspecific glomerular lesions, called minimal change disease (MDC) for corticosteroid-sensitive forms and lesions of Focal Segmental Glomerulosclerosis (FSGS) for severe forms, generally corticosteroid-resistant (CR-INS) (Korbet 1995). The specific complication of this renal disease is its immediate recurrence on the graft (Dantal 1996, Dantal 1995) leading, in 50% of cases, to the failure of the transplantation, condemning these patients to dialysis for life. The origin of this syndrome is currently unknown, but a number of clinical observations tend to show an involvement of the immune system (Shaloub 1974). A number of studies have demonstrated a link between atopy, diet and nephrotic attacks (Lagrue 1982, 1984; Laurent 1987, 1988, 1989). Our team has also shown that plasma exchanges and immunoadsorptions can lead to total or partial remissions, supporting the evidence for the presence of a pathogenic plasma factor linked to immunoglobulins (Dantal 1991, Dantal 1994, Dantal 1998), previously suggested by the observation of immediate recurrence of the initial disease on the graft after renal transplantation (Hoyer 1972, Dantal 1995, Dantal 1996). Finally, more recently the use of anti-CD20 treatment specifically depleting B lymphocytes has made it possible to favorably treat a significant number of patients (Haffner 2009; CaraFuentes 2013; Iijima 2017; Siligato 2018). In 2009, the study of a patient with IPEX syndrome, who displayed INS/MCD, highlighted the importance of regulatory T cells in the pathogenesis of INS (Hashimura 2009). These results were corroborated by two studies showing regulatory T cell dysfunction in INS patients (Prasad 2015; Bertelli 2016). This alteration is also linked to allergies (Stelmaszczyk-Emmel 2015) and could be due to an aberrant microbiota or dysbiosis (Rodrigé 2011; Ohnmacht 2016). The hypothesis of a causality between dysbiosis, lymphocyte alteration and the onset of an INS has recently been raised (Uy 2015; Kaneko 2017). Two studies have shown intestinal dysbiosis in pediatric INS/MCD, with reduction of circulating Tregs (Tsuji 2018, 2020). Hypothesis and objectives Our hypothesis is that in INS/FSGS patients, the alteration of the immune system could be linked to an imbalance of the microbiota. Our objective is to compare the intestinal (and/or urinary) microbiota of the adult INS patient, in nephrotic attacks vs in remission with in parallel a complete monitoring of peripheral immune cells (T and B subtypes, NK, monocytic and dendritic cells) to estimate the possible change in the microbiota between the 2 disease states, and its potential impact on the immune system. The investigators will also compare the microbiota and the immune system of recurrent INS/FSGS patients after transplantation with non-recurrent post-transplant patients. Stages of the study This study should make it possible to 1 / bring together the cohort and the associated samples, necessary to achieve our goals; 2 / carry out the most exhaustive cytometric analysis of the peripheral sub-populations of these patients and 3 / analyze the intestinal and urinary microbiota. We will first collect a group of INS patients (n = 25) in nephrotic surge, then these same patients in remission. The second group to be collected will be a group of recurrent INS/FSGS patients after renal transplantation and a group of non-recurrent INS receiving the same therapeutic protocol (n = 5/5). As control groups, the investigators will collect proteinuric patients of other origin as well as healthy volunteers (n = 10/10). All patients and healthy individuals will sign an informative consent.