Aberrant glycosylation of IgA from patients with IgA nephropathy.
Despite the prominent role of IgA, particularly IgA1, in the pathogenesis of IgA nephropathy (IgAN), the precise role of this molecule in the process remains unclear. Four biotin-conjugated lectins in sandwich-type enzyme-linked immunosorbent assays were devised to determine the glycosylation profiles of total IgA and its subclasses. We took advantage of differential binding properties of these lectins to sugar residues to dissect the oligosaccharide chains O-linked to the hinge and those N-linked to the Fc region of total IgA and IgA subclasses in 47 patients with IgAN and an equal number of controls. The proportion of sialylated IgA1 was higher in patients compared with controls (p < 0.02), whereas IgA2 in patients appeared less well sialylated. A reduction of galactose in pathological IgA as detected by RCA-I became significant after treatment of the molecule with neuraminidase (p < 0.01). Defective galactosylation was also observed for patient IgA1 when it was probed with ECL, a lectin that has a specificity for Gal 1,4 N-acetylglucosamine groupings on N-linked oligosaccharides. The RCA and ECL results, therefore, suggest that increased sialylation on the IgA1 is on O-linked oligosaccharides in the hinge region. This was partly confirmed by a small increase in the binding of PNA to IgA1 from the patient group. This lectin binds preferentially to Gal 1,3 N-acetylgalactosamine groups that are found on O-linked oligosaccharides.
Baharaki
D
D
Laboratory of Immunology, Brest University Medical School Hospital, France.
Dueymes
M
M
Perrichot
R
R
Basset
C
C
Le Corre
R
R
Clèdes
J
J
Youinou
P
P
D005690:Galactose / Q000172:deficiency / Q000378:metabolism; D005922:Glomerulonephritis, IGA / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D007070:Immunoglobulin A / Q000378:metabolism*; D007141:Immunoglobulin Fc Fragments / Q000378:metabolism; D007678:Kidney Glomerulus / Q000378:metabolism
D007070:Immunoglobulin A; D007141:Immunoglobulin Fc Fragments; D005690:Galactose