Lambda Light Chain Predominance Links Glomerular C1q Deposition to Endocapillary Hypercellularity in Ig A Nephropathy
BAIER E. 1, GERSMANN A. 2, HAKROUSH S. 2, TAMPE B. 1
1 Department of Nephrology and Rheumatology, University Medical Center Goettingen, Goettingen, Germany; 2 Department of Pathology, University Medical Center Goettingen, Goettingen, Germany
Involvement of the complement system is a key driver of immune complex-mediated nephritogenicity in immunoglobulin A nephropathy (IgAN), being the most prevalent form of primary glomerulopathy worldwide. Despite growing pathophysiological insights on lambda light chain (LLC) predominance in IgAN, its implications on 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 LLC-predominant biopsy-proven IgAN.
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 levels of creatinine, eGFR, complement C3/ C4 and proteinuria. Oxford-scored lesions mesangial hypercellularity (M), endocapillary hypercellularity (E), segmental sclerosis (S), tubular atrophy (T), crescents (C), and other Banff-score alike lesions were evaluated. Immune histochemistry-detected glomerular deposits of complement factors C1q/ C3c and kappa / LLCs were semiquantitatively scored. Two groups were formed according to the LLC status: LLC-positive (n=20) and LLC-negative (n=17). Clinicopathological correlations were analyzed in both groups regarding glomerular C1q and C3c deposits.
Enrolled patients featured a mean age of 51 (SD: 17) years with median creatinine levels of 1.5 mg/dL. C1q and C3c deposition featured no significant association with serum parameters indicative of kidney injury or proteinuria. In the LLC-negative group, glomerular C1q deposition inversely correlated with systemic C4 levels (beta=-0.602, p=0.011).
We identified E to feature the strongest association with glomerular C1q deposition in the LLC-positive group (beta=0.745, p<0.001). In the LLC-negative group, a significant correlation of C3c deposition and M was identified (beta=0.762, p<0.001).
We here show a correlative pattern of LLC-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 LLC-predominance.