IS THERE AN ASSOCIATION OF MINIMAL CHANGE NEPHROTIC SYNDROME AND HASHIMOTO THYROIDITIS?? Martine K.F. Docx 1 , Johan Vande Walle 2 1 Department of Paediatrics Chronic Diseases Queen Paola Children’s Hospital Antwerp Belgium (martine.docx@zna.be) 2 Department of Paediatric Nephrology and Rheumatology, Safepedrug, Ghent University Hospital, Belgium. 1.Introduction: The association of renal disease with autoimmune thyroid disorders has been reported previously. Renal findings associated with acute thyroiditis presented most commonly as proteinuria ranging from mild to severe nephrotic ranges. The rare association between glomerular disease and Hashimoto thyroiditis may be hypothesized to cross-reacting antigens. In the case of mesangioproliferative glomerulonephritis the target antigen may be thyroglobulin or another thyroid-released antigen that will give deposits in the glomerulus. The simultaneous occurrence of renal glomerular pathologies and Hashimoto thyroiditis suggest that similar immunological mechanisms may be involved in the pathogenesis of the two diseases. 2. Patients. We present 3 patients with minimal change nephrotic syndrome without renal failure and Hashimoto Thyroiditis. The nephrotic syndrome preceded in all 3 patients the Thyroiditis. Patient 1 developed a few months before the Hashimoto Thyroiditis Type 1 Diabetes Mellitus. Patient 3 had an older brother who developed an ADEM syndrome and died. Another sibling developed an aseptic meningitis. All 3 patients are frequent relapsers and are now in remission. Patient Age Sex Age Onset NS HT Antibodies Thyroid Treatment Concomitant autoimmunity 1. O.S. 15.5 y F 5 y 12.6 y Anti-Thyroglobulin Anti-TPO Steroids Diuretics Albumin Cyclosporin Mycophenolate L-Thyroxin Insulin Rituximab 12 y DM type 1 2. A.B. 7 y M 2.5 y 6 y 3. M.R. 4 y 5.1 y 3. Discussion and Hypothesis: Are there Similar Mechanisms in the Pathogenesis in Nephrotic Syndrome (NS) & Hashimoto Thyroiditis ( HS)? Minimal Change NS T&B Cell Dysfunction Cytokine (e.g. IL13) And other circulating factors  Glomerular barrier damage(podocyte foot process effacement) Podocyte malfunction ANGPTL4,CD80 overexpression (autocrine/paracrine) Glomerular filtration barrier impairment(podocyte foot process effacement,loss of GBM charge etc… Adapted from PATHOGENESIS AND GENETICS OF NS by Dr. Aditi Sinha and Dr. Arvin Bagga: An imbalance of Th17 and T regulatory responses allows persistent CD80 activation on podocytes and/or helper responses. Bossowski et al. demonstrated an elevated level of Th17 cells in children with untreated Hashimoto’s disease, which suggests the participation of these cells in the induction and development of the disease. Adapted from Changli Wei and Jochen Reiser . Nephrol Dial Transplant, 2011 PATHOGENESIS OF IDIOPATHIC NS 4.Conclusions. We described 3 patients where minimal change nephrotic syndrome preceded the Hashimoto thyroiditis.Other glomerular diseases associated with Hashimoto’s thyroiditis were mentioned in the literature:IgA nephropathy, membranoproliferative glomerulonephritis,focal segmental glomerulosclerosis and myloidosis.In the literature we found that an imbalance of Th 17 is found in both diseases.(see Fig 2-3). Patients with pediatric nephrotic syndrome were found to have an increased number of Th17 cells .Wang et al. concluded that Th17/IL17 may contribute to the pathogenesis of PNS by decreasing the podocalyxin level and inducing monocyte apoptosis.In Hashimoto thyroiditis histopathological examinations showed a relationship between the concentration of IL17 and stromal fibrosis. So to conclude Th17 lymphocytes serve as a pathogenic factor in the development of various autoimmune diseases. A possible hypothesis could be the increased number of Th17 cells we found in both diseases what a possible explanation can be for the association of minimal change nephrotic syndrome and Hashimoto Thyroiditis in our patients. Further research is needed. References: 1.Kazunari Kaneko et al. Pathogenesis of childhood idiopathic nephrotic syndrome: a paradigm shift from T-cells to podocytes. WJP. 2015;11(1):21-28. 2. A. Bossowski, M. Moniuszko, M. Dabrowska et al., “Lower proportions of CD4+CD25high and CD4 +FoxP3, but not CD4+CD25+CD127low FoxP3+T cell levels in children with autoimmune thyroid diseases,” Autoimmunity, vol. 46, no. 3, pp. 222–230, 2013. 3.Pyzik A et al. Immune Disorders in Hashimoto’s Thyroiditis:What do we know so far? Journal of Immunology Research.2015; Address for correspondence to : Martine K.F.Docx MD  Queen Paola Children’s Hospital  Lindendreef 1, 2020 Antwerp, Belgium.  mail: martine.docx@zna.be