N-Glycan Remodelling and Lectin Pathway Activation in the Pathogenesis of IgA Nephropathy in Nigerian Patients

IgA nephropathy, the most common primary glomerulonephritis globally, is driven by aberrant O-glycosylation of the IgA1 hinge region, leading to lectin pathway complement activation and glomerular injury. This study investigates N-glycan remodelling of serum IgA1, lectin pathway complement activation markers, and their biochemical relationship to disease severity in Nigerian IgA nephropathy patients. A multi-centre case-control design was employed across nephrology units in Oyo, Lagos, and Cross River States, recruiting 70 biopsy-confirmed IgA nephropathy patients, 70 patients with other glomerulonephritides, and 70 healthy controls. Serum IgA1 O-glycoform characterisation was performed by lectin ELISA using Helix aspersa agglutinin specific for galactose-deficient IgA1. N-glycan profiling of circulating IgA1 was conducted by 2-AA labelled HILIC-UHPLC-fluorescence detection. Mannose-binding lectin, MASP-2, and C3 were measured to characterise lectin pathway activation. Oxford classification scoring from biopsy reports stratified glomerular injury severity. Multi-variate models linked glycobiochemical parameters to renal prognosis indices. This study constitutes the first characterisation of IgA1 glycopathology in Nigerian renal patients and generates original biochemical knowledge for a mechanistically defined nephrology condition in West Africa. Keywords: IgA nephropathy, O-glycosylation, lectin complement pathway, glycobiology, glomerulonephritis.