Adult-Onset Semaphorin-3B–Associated Membranous Nephropathy: A Diagnostic Pitfall Resolved by Antigen-Based Classification

Background Semaphorin-3B (SEMA3B)–associated membranous nephropathy (MN) is a recently described, antigen-defined subtype of MN, predominantly reported in pediatric patients, but also in young adults. Cases of post-kidney transplant recurrent SEMA3B-associated have also been reported in both children and adults. Case Presentation We report a 40-year-old woman who presented with nephrotic syndrome and was concurrently diagnosed with celiac disease. Kidney biopsy demonstrated stage I membranous nephropathy with IgG-dominant immune deposits and negative serum anti-PLA 2 R antibodies. Despite a gluten-free diet, optimized supportive therapy, and corticosteroid treatment, nephrotic-range proteinuria persisted. Rituximab therapy resulted in complete clinical remission. Subsequent laser microdissection and mass spectrometry analysis of the kidney biopsy identified SEMA3B as the target antigen, establishing the diagnosis of SEMA3B-associated MN. Conclusions This case highlights that adult-onset SEMA3B-associated membranous nephropathy may coexist with autoimmune disorders that complicate etiologic interpretation. Antigen identification by laser microdissection and mass spectrometry provided retrospective clarification of the underlying disease process and supported classification within the current antigen-based framework. This case illustrates the value of antigen identification in PLA 2 R-negative membranous nephropathy when alternative etiologies are being considered.