Mesangial Cell-Specific Antibodies Are Central to the Pathogenesis of Lupus Nephritis
To analyze O-linked oligosaccharides (O-glycans) in the hinge region of IgA1 in IgA nephropathy (IgAN), the reactivity of IgA1 to jacalin, which specifically binds to O-glycans, was investigated. Initially, renal biopsy specimens from 5 patients with IgAN and 3 patients with other renal diseases were investigated in an immunofluorescence study with jacalin, monoclonal antihuman IgA1 and IgA2 antibodies. All of the renal biopsy specimens of IgAN and none of other renal diseases were positively stained by both FITC-labeled jacalin and monoclonal anti-IgA1 antibody. The glomerular staining patterns of FITC-jacalin were similar to those of the monoclonal anti-IgA1 antibody. IgA2 was negative in all specimens. Based on the positive reactivity of deposited IgA1 to jacalin, the binding ability of serum IgA1 to jacalin was evaluated by inhibition assay using D-galactose in patients with IgAN (n = 58), other primary glomerulonephritides (PGN) (n = 41), and healthy controls (n = 52). The frequencies of the patients with serum IgA1 having a high affinity for jacalin were significantly greater in IgAN (19/58, 32.8%) compared with the healthy controls (2/52, 3.8%) and other PGN (4/41, 9.8%). These results suggested that the increased reactivity of O-glycan(s) in the IgA1 hinge region to jacalin is due to an unusual glycosylation of serum IgA1 in IgAN.