O-glycosylation of serum IgA1 antibodies against mucosal and systemic antigens in IgA nephropathy.
In IgA nephropathy (IgAN), serum IgA1 with abnormal O-glycosylation deposits in the glomerular mesangium. The underlying mechanism of this IgA1 O-glycosylation abnormality is poorly understood, but recent evidence argues against a generic defect in B cell glycosyltransferases, suggesting that only a subpopulation of IgA1-committed B cells are affected. For investigation of whether the site of antigen encounter influences IgA1 O-glycosylation, the O-glycosylation of serum IgA1 antibodies against a systemic antigen, tetanus toxoid (TT), and a mucosal antigen, Helicobacter pylori (HP), was studied in patients with IgAN and control subjects. Serum IgA1 was purified from cohorts of patients with IgAN and control subjects with HP infection and after systemic TT immunization. The IgA1 samples were applied to HP- and TT-coated immunoplates to immobilize specific antibodies, and IgA1 O-glycosylation profiles were assessed by binding of the O-glycan-specific lectin Vicia villosa using a modified ELISA technique. Although total serum IgA1 had raised lectin binding in IgAN, the O-glycosylation of the specific IgA1 antibodies to TT and HP did not differ between patients and control subjects. In both groups, IgA1 anti-HP had higher lectin binding than IgA1 anti-TT. This study demonstrates that IgA1 O-glycosylation normally varies in different immune responses and that patients produce the full spectrum of IgA1 O-glycoforms. IgA1 with high lectin binding was produced in response to mucosal HP infection in all subjects. The raised circulating level of this type of IgA1 in IgAN is likely to be a consequence of abnormal systemic responses to mucosally encountered antigens rather than a fundamental defect in B cell O-glycosylation pathways.
Smith
Alice C
AC
University of Leicester Department of Infection, Immunity and Inflammation, and John Walls Renal Unit, Leicester General Hospital, Leicester, United Kingdom. aa50@le.ac.uk
Molyneux
Karen
K
Feehally
John
J
Barratt
Jonathan
J
D000328:Adult; D001402:B-Lymphocytes; D005260:Female; D005922:Glomerulonephritis, IGA / Q000097:blood / Q000276:immunology*; D006031:Glycosylation; D016481:Helicobacter Infections / Q000276:immunology*; D016480:Helicobacter pylori / Q000276:immunology; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood / Q000378:metabolism*; D037102:Lectins / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008895:Milk, Human / Q000276:immunology; D009092:Mucous Membrane / Q000276:immunology*; D013745:Tetanus Toxoid / Q000276:immunology
D007070:Immunoglobulin A; D037102:Lectins; D013745:Tetanus Toxoid