Anti-α-galactosyl antibodies and immune complexes in children with Henoch–Schönlein purpura or IgA nephropathy

Abstract

Episodes of hematuria in IgA nephropathy or Henoch-Schönlein purpura are frequently associated with microbial infections. Some of those infectious agents bear alpha-galactosyl residues on their cell surface. These observations prompted us to determine, by passive hemagglutination, the titers of natural anti-galactosyl antibodies in the serum of children presenting with Henoch-Schönlein purpura (10 cases) or IgA nephropathy (7 cases). Antibody titers of normal subjects (103 cases), children with a pharyngitis of unknown etiology (7 cases), and children exhibiting mesangial IgA deposits but no hematuria at the time of testing (6 cases) ranged from 1:20 to 1:80. Elevated titers (greater than 1:80) were observed in nine of 11 patients with mesangial IgA deposits and micro- or macroscopic hematuria, in nine of 19 children with other evolutive glomerular diseases (5 cases of acute glomerulonephritis and 4 cases of minimal change disease), and in most subjects presenting with a M. pneumoniae (4/5 cases) or a E. Coli (4/5 cases) infection. Antibody titers decreased after incubation of normal and pathological sera with D-galactose (10 mM) or with alpha-galactosyl-glucoside (10 mM), but not with D-glucose (10 mM). The anti-alpha-galactosyl antibodies purified, by affinity chromatography, from sera of 10 normal children, 10 pathological controls and four children with mesangial IgA deposits without hematuria belonged to IgG class. In contrast, both IgG and IgA anti-alpha-galactosyl antibodies were detected in six of six patients with mesangial IgA deposits and hematuria. The IgA content of immune complexes detected in those patients decreased after incubation of sera with alpha-galactosyl-glucoside, but not with D-glucose.(ABSTRACT TRUNCATED AT 250 WORDS)

Induction of Cytolytic Anti-Gal Antibodies in α-1,3-Galactosyltransferase Gene Knockout Mice by Oral Inoculation withEscherichia coliO86:B7 Bacteria

“…Binding of anti-Gal IgA to the pili of Neisseria meningitidis has been shown to compete with anti-Gal IgG binding and to inhibit complementmediated cytolysis of piliated strains (12). Infection with E. coli and other gram-negative bacteria has been associated with elevated anti-Gal antibodies and autoimmune disease due to IgA immune complex deposition in children with HenochSchönlein purpura or IgA nephropathy (5).…”

Increased Immunogenicity of Tumor-Associated Antigen, Mucin 1, Engineered to Express α-Gal Epitopes: A Novel Approach to Immunotherapy in Pancreatic Cancer

“…Anti-Gal is an IgG antibody (Ab) that is present in large amounts in normal subjects and patients with malignancies, comprising ∼1% of serum-circulating IgG (16)(17)(18). Anti-Gal Ab specifically interacts with α-gal epitopes on cell surface glycolipids and glycoproteins, and it is produced throughout life due to antigenic stimulation by bacteria of the gastrointestinal flora (19).…”

Antimouse Laminin Antibodies in IgA Nephropathy and Various Glomerular Diseases

“…Since Towbin et al [14] previously reported that the circulating antibody to mouse laminin in Chagas' disease, American cutaneous leishmania sis and normal individuals recognizes terminal galactosyl-a il ->3)-galactose epitopes and since Davin et al [15] reported earlier the presence of anti-a-galactosyl antibody in sera from IgA neph ropathy patients, the possibility exists that the IgA antimouse lam inin antibody we detected might recognize the same epitopes as anti-a-galactosyl antibody. To elucidate this possibility, inhibition ELISA using melibiose (which contains an a-galactosyl residue) and treatment of the solid-phase mouse laminin by a-galactosidase were studied.…”