Protocadherin FAT1-associated membranous nephropathy after hematopoietic stem cell transplantation-a cohort study with clinico-pathological correlations.

BACKGROUND

The identification of causative antigens for membranous nephropathy (MN) has revolutionized the comprehension of the pathophysiology of this autoimmune disease and its management. Recently, some studies described protocadherin FAT1 (FAT1) as a causal antigen in the context of hematopoietic stem cell transplantation (HSCT). The aim of this study was to investigate the large Viennese kidney biopsy collection at the Department of Pathology of the Medical University of Vienna and explore MN cases after HSCT for the causative antigen.

METHODS

Fifteen patients were identified with MN in diagnostic renal biopsies for proteinuria/nephrotic syndrome after HSCT between 2001 and 2024. Cases were reviewed and tested for the expression of FAT1 by immunofluorescence specifically.

RESULTS

Immunofluorescence showed that 12 out of 15 patients with MN had FAT1 expression, appearing 2.3 years after HSCT. In three patients without FAT1 expression, MN appeared 3.8 years after HSCT, with one testing positive for phospholipase A2 receptor (PLA2R) and two with unknown antigens. Serum creatinine for FAT1+ MN was 1.2 mg/dl, while FAT1- MN was 1.3 mg/dl. Proteinuria was 8 g/g compared to 10.4 g/g, respectively. IgG4 positivity was seen in 30% of FAT1+ MN cases. Over a follow up of 5.2 years, of the seven FAT1+ MN patients treated with rituximab, four achieved complete remission, two partial remission, and one was non-responsive.

CONCLUSION

This hitherto largest single-center-cohort solidifies FAT1 as a causative antigen for MN in the setting of HSCT. However, not all post-HSCT-MN are related to FAT1.