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Abstract: TH-PO536

Lambda Light Chain Predominance Links C1q Deposition to Endocapillary Hypercellularity in IgA Nephropathy

Session Information

Category: Glomerular Diseases

  • 1401 Glomerular Diseases: From Inflammation to Fibrosis

Authors

  • Baier, Eva, Universitatsmedizin Gottingen Klinik fur Nephrologie und Rheumatologie, Gottingen, Niedersachsen, Germany
  • Tampe, Bjoern, Universitatsmedizin Gottingen Klinik fur Nephrologie und Rheumatologie, Gottingen, Niedersachsen, Germany
Background

Involvement of the complement system is a key driver of immune complex-mediated nephritogenicity in immunoglobulin A nephropathy (IgAN), being the most prevalent primary glomerulopathy worldwide. Despite growing insights on the pathophysiological relevance of lambda (λ) light chain (LC) predominance in IgAN, implications of glomerular complement deposition remain largely elusive. Therefore, we here aimed to systematically assess the correlative pattern of clinicopathological findings and glomerular complement C1q and C3c deposits in λ-LC predominant biopsy-proven IgAN.

Methods

A total of 37 patients with biopsy-proven IgAN obtained between 2016 and 2021 were retrospectively included in a single center observational study. Clinical data assessment comprised age, sex, serum creatinine levels, blood urea nitrogen, eGFR, complement C3/ C4 and proteinuria. Oxford-scored lesions mesangial (M) and endocapillary hypercellularity (E), segmental sclerosis (S), tubular atrophy (T), crescentic formations (C), and other lesions scored analogous to the Banff classification were evaluated. Immune histochemistry-detected glomerular deposits of complement factors C1q/ C3c and kappa (κ)/ λ LCs were semiquantitatively scored. Two groups were formed according to the λ-LC status: λ-LC positive (n=20) and λ-LC negative (n=17). Clinicopathological correlations were analyzed in both groups regarding glomerular C1q and C3c deposits by means of multivariable linear regression.

Results

Enrolled patients featured a median creatinine level of 1.5 mg/dL. C1q and C3c deposition featured no significant association with serum parameters indicative of kidney injury or proteinuria. We identified endocapillary hypercellularity to feature the strongest association with glomerular C1q deposition in the λ-LC positive group (ρ=0.7; β=0.745, p<0.001). In the λ-LC negative group, a significant correlation of C3c deposition and mesangial hypercellularity was identified (ρ=0.6; β=0.762, p<0.001).

Conclusion

We here show a correlative pattern of λ LC-associated deposition of complement factors C1q and C3c in distinct histopathological features of IgAN implying an involvement of the classical pathway in the preset of λ-LC predominance.