#3585 FAT1 ANTIGEN IN PATIENTS WITH MEMBRANOUS NEPHROPATHY AFTER HEMATOPOIETIC STEM CELL ALLOTRANSPLANTATION: A CASE SERIES
Authors: Kovačić Ines Bosnić , Laganovic Mario , Dika Zivka , Ćorić Marijana , Bulimbasic Stela , Peric Zinaida , Grkovic Lana , Vrhovac Radovan , Durakovic Nadira , Jelakovic Bojan , Brinar Ivana Vukovic 
Published: June 2023

Background and Aims

Nephrotic syndrome (NS) is a rare complication of haematopoietic stem cell transplantation (HSCT). When it occurs, it usually develops after cessation of immunosuppressive therapy, which is why it is commonly denominated as a renal form of chronic graft-versus-host disease. Membranous nephropathy (MN) is the most common pathological finding. The protocadherin FAT1 antigen is a novel antigen identified only in patients with MN who have undergone allogeneic HSCT. PLA2R and NELL1 antigens can also be found, even though they are rare and not specific to HSCT-associated MN. The aim of this study was to present a case series of allogeneic HSCT-associated MN, the treatment, outcomes and presence of a novel antigen specifically detected in this population.

Method

All patients with full blown NS due to MN after HSCT in UHC Zagreb were enrolled. Kidney biopsy was performed and examined by light, immunofluorescence and electron microscopy. Biopsy samples were sent to Renal Pathology Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic for detection of FAT1 antigen in biopsy tissue samples

Results

In last 30 years there had been 1302 HSCT in UHC Zagreb and three of them developed MN. The first two patients were treated with allogeneic HSCT for acute myeloid leukaemia (AML). Both developed NS after cessation of GVHD prophylaxis, after 1 and 8 months respectively. The first patient's kidney function was preserved, while the second patient's was reduced. Kidney biopsy showed MN. Thorough examination found no secondary cause of the disease. In the first patient, complete remission (CR) was achieved after 5 months of steroids, 2 boluses of cyclophosphamide (CP) and cyclosporine treatment. The second patient reached partial remission (PR) after 6 months of steroid treatment and oral CP. Immunosuppression was terminated due to infectious complications. CR was achieved after an additional 8 months while the patient was not taking immunosuppressants. Both patients remained in CR during the follow-up period.

The third patient with acute lymphoblastic leukaemia (ALL) underwent a related peripheral blood HSCT. Sixteen years later, he developed NS with preserved renal function and was diagnosed with MN. Apart from thyroid disease, no secondary cause was detected and he was treated with rituximab. Partial remission (PR) was achieved after 24 months of therapy.

Anti-PLA2R antibodies were negative in all three cases. Tissue samples from patients 1 and 2 were positive for FAT1 antigen using laser microdissection and tandem mass spectrometry (MS/MS) of glomeruli. The third patient was negative for FAT1. Clinical and biopsy findings in our cohort of HSCT-associated MN are summarised in Tables 1 and 2.

Conclusion

MN can occur at different points in time, sometimes even years, after HSCT. It can be successfully treated with steroids and immunosuppressants, achieving long-term remission. Most patients with HSCT-associated MN are FAT1-positive, although it is not the only antigen associated with MN in HSCT patients. In the future, serum testing for anti-FAT1 antibodies in patients with HSCT could be of similar significance in diagnosing FAT1-associated MN as PLA2R antibodies are for PLA2R-associated MN.