IgM as a novel predictor of disease progression in secondary focal segmental glomerulosclerosis

Abstract

AimTo determine the role of immunoglobulin M (IgM) deposits in clinical manifestations, disease outcome, and treatment response of idiopathic and secondary focal segmental glomerulosclerosis (FSGS).MethodsKidney biopsy specimens of 171 patients diagnosed with FSGS (primary and secondary) and 50 control patients were retrospectively included in the study. For each patient, clinical and outcome data were obtained and compared to morphological parameters, including immunofluorescence analysis of mesangial IgM and complement 3 (C3) deposits analyzed on kidney biopsy samples.ResultsThere were significant positive correlations between IgM and C3 deposition in secondary FSGS (P < 0.001) and between IgM and mesangial deposits detected by electron microscopy in secondary FSGS (P = 0.015), which indicated that higher IgM deposition correlated with higher C3 deposition and mesangial deposits only in secondary FSGS. Patients with secondary FSGS and the deposition of IgM showed inferior renal outcomes at earlier time points in comparison with patients with negative IgM expression (P = 0.022).ConclusionsWe detected a positive correlation between IgM and C3 in secondary FSGS. The association between IgM deposition and worse renal outcome in secondary FSGS indicates that IgM may play a role in the progression of this disease.

Co-Deposition of IgM and C3 May Indicate Unfavorable Renal Outcomes in Adult Patients with Primary Focal Segmental Glomerulosclerosis

“…Until recently, significance of these pathological findings has been unclear, yet Strassheim et al [12] demonstrated that IgM deposits activated the classical and alternative pathways (APs) of the complement system within the glomerulus and contributed to disease progression in adriamycin nephropathy, an animal model of FSGS. The importance of these depositions on the disease course of patients with primary FSGS is still obscure [8, 13]; we therefore aimed to investigate the significance of glomerular IgM and C3 deposition on clinical and pathological features and outcomes of adult patients with primary FSGS.…”

Clinical relevance of glomerular IgM deposition in patients with lupus nephritis

“…On the basis of the above relevance of glomerular IgM deposition in patients with lupus nephritis, it is important to evaluate the predictive value of glomerular IgM deposition for long-term renal outcome in lupus nephritis. Recently, several studies showed that IgM deposition predicted renal outcome in patients with IgAN, FSGS and diabetic nephropathy [7,9,22,23].…”

“…In another animal model of adriamycin-induced focal segmental glomerulosclerosis (FSGS), IgM deposition activated the complement system and mediated glomerular injury [6]. In the subsequent clinical studies, IgM deposition independently associated with worse renal outcomes in patients with various glomerular diseases, including FSGS, IgA nephropathy (IgAN), and diabetic nephropathy (DN) [7][8][9].…”

Clinical characteristics and outcomes of idiopathic membranous nephropathy with glomerular IgM deposits

“…Consistent with our study, it has been shown that patients who have IgAN with IgM deposition have a higher C1q deposition rate and more severe Oxford classi cation (statistically signi cant differences in mesangial proliferation, endocapillary proliferation, segmental sclerosis, and crescents) [22]. There should be no signi cant difference in immune complex deposition in the glomeruli in patients with typical FSGS lesions, thin basement membrane nephropathy, and mild glomerular lesions, but one study showed that patients with FSGS lesions had a signi cantly higher IgM deposition rate than patients with thin basement membrane nephropathy and mild glomerular lesions (55.4% vs. 30.0%) [23]. In addition, other studies have shown that patients with IgM nephropathy who present with only IgM deposits in the mesangial area are more likely to progress to FSGS lesions as con rmed by repeat renal biopsy [24][25][26].…”