Significant glomerular IgM deposition predicts poorer kidney outcomes in lupus nephritis compared with other forms of immune complex deposits.

Objective: Glomerular immune complex deposition plays a central role in lupus nephritis (LN), but the prognostic relevance of individual immunoglobulin components remains unclear. This study aimed to investigate the clinical impact of glomerular immunoglobulin M (IgM) deposition intensity on patient outcomes.

Methods: This retrospective cohort study analysed 952 biopsy-proven LN patients (1996-2019) from the First Affiliated Hospital of Sun Yat-sen University. A semiquantitative scoring system stratified glomerular immunoglobulin G (IgG), immunoglobulin A (IgA), IgM, complement 3 (C3) and complement component 1q (C1q) deposition into low (-/+) and high (++ to ++++) groups. The primary outcome was a composite of doubling of serum creatinine from baseline or the development of end-stage renal disease (ESRD). The secondary outcome was all-cause mortality. A multivariable Cox regression model was used to adjust for baseline clinical and pathological factors.

Results: Among the studied immune complexes, only high glomerular IgM deposition was significantly associated with adverse renal outcomes (p=0.025). These patients had higher baseline Systemic Lupus Erythematosus Disease Activity Index scores (SLEDAI) (16 (12-20) vs 15 (12-18), p<0.001), more severe histopathological features (including proliferative glomerulonephritis, endocapillary hypercellularity, leucocyte infiltration and microthrombi), and profound complement activation (lower median serum C3 and complement 4 (C4) levels, both p<0.05). High glomerular IgM deposition also correlated with high IgA (r=0.48) and C3 (r=0.40) deposition (both p<0.01). Multivariable analysis revealed that high glomerular IgM deposition remained an independent predictor of renal progression (adjusted HR=1.485, 95% CI 1.040 to 2.119, p=0.029).

Conclusion: High glomerular IgM deposition emerged as an independent prognostic marker for adverse renal outcomes in LN, potentially outperforming other individual immune complexes. These findings highlight the pathogenic significance of IgM in LN and support its value in risk stratification and treatment guidance.