Phénotypes lipodystrophiques (analyses anthropométriques, métaboliques et immuno-inflammatoires en comparaison à des sujets témoins obèses)

Introduction: Le diagnostic des lipodystrophies non-HIV peut s avérer difficile, d autant que des formes frontières avec le diabète de type 2 et l obésité ont été décrites (Diabetes Care 2013).Objectif : Etudier les caractéristiques anthropométriques, métaboliques et immuno-inflammatoires de sujets lipodystrophiques en comparaison à des sujets obèses et des témoins sains.Matériels et méthodes : Cette étude prospective (PHRC 2009_09/0941) porte sur une population initiale de 108 patients, réduite à 94 après ajustement sur l âge et le sexe, et répartis en 3 groupes : 52 sujets lipodystrophiques (32 avec composante lipoatrophique dont 16 mutés pour le gène de la Lamine A/C (LM) et 16 non mutés (LNM), 6 Launois-Bensaude et 16 autres types de lipodystrophies), 28 sujets obèses (dont 12 diabétiques) et 13 témoins (T). Les caractéristiques cliniques, métaboliques et immuno-inflammatoires ont été recueillies. Les paramètres anthropométriques (masse grasse (MG), masse maigre (MM), masse hydrique, T-score entier, graisse abdominale totale (GAT), graisse intra-abdominale (GIA)) ont été obtenus par absorptiométrie biphotonique, impédancemétrie et IRM abdominale. Les résultats des 3 groupes de patients ont été comparés 2 à 2, puis entre les sous-groupes de patients.Résultats : Les 3 groupes diffèrent par les paramètres de MG (p<0.0001), MM (p<0.0001), rapports MG/MM (p<0.0001), Fat Mass ratio (FMR=MG tronc/MG membres inférieurs) (p<0.001), masse hydrique (p<0.001), GIA (p<0.0001), GAT (p<0.00001) et rapport GIA/GAT (p<0.001). L analyse des sous-groupes met en évidence une différence significative de la leptine (sauf entre LM et T), de la glycémie (sauf entre LM, LNM et obèses), de l insuline uniquement entre LM ou LNM et T, des anomalies inflammatoires non spécifiques chez les lipodystrophiques non mutés et les obèses et des anomalies immunologiques spécifiques des lipodystrophiques mutés sur le taux de lymphocytes TCD4+ et des CD25+ (entre LM et T, les CD25+ différenciant également les LM des LNM (p<0.05)).Conclusion : Les 4 rapports qui différenciaient les mieux les sous-groupes par rapport aux témoins sont GIA/GAT, MG/MM du tronc, Leptine/GAT et le FMR. Leur combinaison permet de quantifier le type de déséquilibre adipo-musculaire entre les 4 sous-groupes pathologiques. Les anomalies immuno-inflammatoires contribuent probablement au déterminisme de ces déséquilibres dont la compréhension devrait ouvrir de nouvelles perspectives étiologiques et thérapeutiques.LILLE2-BU Santé-Recherche (593502101) / SudocSudocFranceF

Immunosuppressive drugs and fertility.

International audienceImmunosuppressive drugs are used in the treatment of inflammatory and autoimmune diseases, as well as in transplantation. Frequently prescribed in young people, these treatments may have deleterious effects on fertility, pregnancy outcomes and the unborn child. This review aims to summarize the main gonadal side effects of immunosuppressants, to detail the effects on fertility and pregnancy of each class of drug, and to provide recommendations on the management of patients who are seen prior to starting or who are already receiving immunosuppressive treatment, allowing them in due course to bear children. The recommendations for use are established with a rather low level of proof, which needs to be taken into account in the patient management. Methotrexate, mycophenolate, and le- and teri-flunomide, cyclophosphamide, mitoxanthrone are contraindicated if pregnancy is desired due to their teratogenic effects, as well as gonadotoxic effects in the case of cyclophosphamide. Anti-TNF-alpha and mTOR-inhibitors are to be used cautiously if pregnancy is desired, since experience using these drugs is still relatively scarce. Azathioprine, glucocorticoids, mesalazine, anticalcineurins such as cyclosporine and tacrolimus, ß-interferon, glatiramer-acetate and chloroquine can be used during pregnancy, bearing in mind however that side effects may still occur. Experience is limited concerning natalizumab, fingolimod, dimethyl-fumarate and induction treatments. Conclusion: At the time of prescription, patients must be informed of the possible consequences of immunosuppressants on fertility and of the need for contraception. Pregnancy must be planned and the treatment modified if necessary in a pre-conception time period adapted to the half-life of the drug, imperatively in relation with the prescriber of the immunosuppressive drugs

The challenge of HLA donor specific antibodies in the management of pancreatic islet transplantation: an illustrative case-series

Abstract Islet transplantation is a unique paradigm in organ transplantation, since multiple donors are required to achieve complete insulin-independence. Preformed or de novo Donor Specific Antibodies (DSA) may target one or several donor islets, which adds complexity to the analysis of their impact. Adult patients with type 1 diabetes transplanted with pancreatic islets between 2005 and 2018 were included in a single-center observational study. Thirty-two recipients with available sera tested by solid-phase assays for anti-HLA antibodies during their whole follow-up were analyzed. Twenty-five recipients were islet-transplantation-alone recipients, and 7 islet-after-kidney recipients. Seven recipients presented with DSA at any time during follow-up (two with preformed DSA only, one with preformed and de novo DSA, 4 with de novo DSA only). Only islet-transplantation-alone recipients presented with de novo DSA. Three clinical trajectories were identified according to: 1/the presence of preformed DSA, 2/early de novo DSA or 3/late de novo DSA. Only late de novo DSA were associated with unfavorable outcomes, depicted by a decrease of the β-score. Islet transplantation with preformed DSA, even with high MFI values, is associated with favorable outcomes in our experience. On the contrary, de novo DSA, and especially late de novo DSA, may be associated with allograft loss

Erratum. Ten-Year Outcome of Islet Alone or Islet After Kidney Transplantation in Type 1 Diabetes: A Prospective Parallel-Arm Cohort Study. Diabetes Care 2019;42:2042-2049.

The names of the working groups that collaborated in the study reported in this article were inadvertently omitted from the byline. The corrected byline should