Immunofluorescence Patterns in IgAN are Associated With Active, Necrotizing Lesions

Area of Science:

• Nephrology
• Immunology
• Pathology

Background:

• IgA nephropathy (IgAN) exhibits significant heterogeneity, complicating treatment decisions.
• Current therapeutic strategies often lack personalization.
• Understanding distinct immunological profiles is vital as new targeted therapies emerge.

Purpose of the Study:

• To identify distinct immunological endotypes in IgA nephropathy.
• To determine the association of these endotypes with severe histological lesions, particularly glomerular necrosis.
• To inform precision medicine approaches in IgAN management.

Main Methods:

• Retrospective analysis of 284 patients with biopsy-proven IgAN.
• Exclusion of secondary forms of IgAN.
• Stratification into three immunofluorescence endotypes: "classic", "full-house", and "complement".
• Multivariable logistic regression to identify factors associated with glomerular necrosis.

Main Results:

• The "full-house" IgAN phenotype (26.1%) was associated with a significantly higher prevalence of glomerular necrosis (30.1%), 5 times greater than the "classic" pattern.
• The "full-house" pattern was the strongest independent predictor of necrosis (OR: 11.32, P < 0.001).
• The "complement" pattern (9.2%) identified a distinct subgroup with severe functional decline and the worst baseline renal function (median eGFR 20 ml/min/m²).

Conclusions:

• Immunohistological subtyping reveals critical IgAN endotypes missed by standard MEST-C scores.
• "Full-house" pattern serves as a marker for necrotizing lesions, potentially linked to IgG-mediated complement activation.
• "Complement" pattern indicates advanced functional loss, highlighting distinct immunopathological subgroups for potential treatment stratification.