Autologous Stem-Cell Transplant Inducing Autoimmunity Leading to Membranous Nephropathy

Introduction: We present a rare case of amyloidosis and autologous stem cell transplant (auto-SCT) two years prior presenting with new nephrotic range proteinuria due to secondary immune complex vasculopathy and membranous nephropathy. Case Description: A 67-year-old woman with HTN, HLD, AL amyloidosis (diagnosed 4 years ago, treated with CyBorD-Daratumaumab for 1.5 years) presented with worsening proteinuria. Peak proteinuria was 800mg. Auto-SCT was 2.5 years earlier with severe engraftment syndrome (fever, rash, diarrhea) diagnosed by colon biopsy consistent with autologous GVHD treated with prednisone for 2 years, compared to typical 1-2 week therapy, given recurrence of diarrhea with cessation of steroids. Repeat colonoscopy negative for GVHD but inflammatory cecal mass noted while on 5mg Prednisone daily. Prednisone was stopped 4 months prior and patient then noted foamy urine, increased fatigue, mild nausea, intermittent water stools. Lab work showed ACR 3.4g up from 15mg one year ago and UPC 6.4g, moderate hematuria, urine sediment with 1 dysmorphic RBC, stable creatinine 0.97, albumin 2.8, negative ANA, negative anti-PLA2R, positive hepatitis B surface antibody (vaccinated), and negative hepatitis C and CMV. Amyloid noted to be in remission on blood work. Renal biopsy showed membranous nephropathy (stage I-II) and glomerular and arteriolar IgG, IgA, C3, and C1q immune deposits by IF. 40% global and 10% FSGS, minimal glomerular and vascular amyloid deposits, moderate-severe interstitial fibrosis, and tubular atrophy noted. Diagnosis of autoimmune IC type disease with secondary membranous in auto-SCT was made and treatment started with Rituximab and steroids. Discussion: Autologous GVHD is thought to be similar to autoimmune syndrome and has been documented in the GI tract and skin. Studies have detected autoantibodies after SCT with chronic GVHD, providing evidence for B-cell involvement. Here the proteinuria is driven by membranous nephropathy with polyclonal immune complex deposits. Autoimmunity is likely from ASCT (can happen with infections, e.g. hepatitis B, but it was negative). Steroids and Rituximab can be used to treat auto-SCT-associated antibody mediated autoimmune MN. This case highlights not only a rare presentation but also the importance of repeat biopsy for diagnosing another cause, especially if other markers of amyloidosis are negative and history doesn’t support amyloidosis.