A Clinicopathological Study of IgA Variant-Proliferative Glomerulonephritis with Monotypic Ig Deposits (PGNMID)

Background: Proliferative glomerulonephritis with monotypic immunoglobulin deposits (PGNMID) is a rare form of monoclonal gammopathy of renal significance (MGRS) related to glomerular non-organized monotypic Ig deposits, usually IgG. The IgA variant of PGNMID has been rarely described. We aimed atdescribing a large cohort of IgA-PGNMID to detail population characteristics, treatment, and renal and hematological outcome. Methods: We conducted a multicentric retrospective study of all French patients with monotypic IgA glomerular deposits with a PGNMID diagnosis between May 2012 and May 2023. Patients were classified in two groups according to the presence of a detectable monotypic IgA component (blood, urine, or blood marrow). Renal, and hematological, baseline characteristics and long-term follow-up were analyzed. Results: Forty-three patients were identified. Eighteen (41,8%) patients had a detectable monoclonal IgA clone (IgA-MGRS) and 25 (58,1%) (unproven MGRS) had no identified clone in blood and/or blood marrow. Most patients were men (65%), and the mean age was 52 years. Renal function impairment was frequent at diagnosis (DFG < 60 ml/min in 77,7 % and 68%, in the IgA-MGRS and unproven MGRS groups, respectively) and proteinuria > 1 g/g in 15/18 (83,3%) and 22/25 (88%) cases, in the IgA-MGRS and unproven MGRS groups, respectively. There were no significant differences between groups at baseline, except for hypertension. After treatment with anti-plasmocytic drugs, patients with a detectable clonal IgA and eGFR > 30 ml/min/m2 had a correlation between hematological and renal response after one year follow-up (Fisher p=0,04). 3/7 patients (42,8 %) had disease recurrence after renal transplantation, and all of them had hematological relapse. Four patients developed overt malignancy with MM. At last follow-up, renal survival was significantly lower in IgA-MGRS group than unproven MGRS and primitive polytypic IgA nephropathy groups. Conclusion: In conclusion, IgA-PGNMID is a distinct entity from IgA nephropathy, with renal outcome correlated with hematological outcome after anti plasmocytic treatment. A pathogenic plasma cell clone is identified in 42% cases and is associated with a worse renal prognosis.