title: Both IgA nephropathy and alcoholic cirrhosis feature abnormally glycosylated IgA1 and soluble CD89-IgA and IgG-IgA complexes: common mechanisms for distinct diseases.
abstract: Abnormalities of IgA arise in alcoholic cirrhosis, including mesangial IgA deposits with possible development of secondary IgA nephropathy (IgAN). Since little is known about circulating immune complexes in cases of secondary IgAN, we analyzed IgA-associated parameters in the serum of 32 patients with compensated or advanced alcoholic cirrhosis. Galactose deficiency and decreased sialylation of IgA1, as well as increased amounts of abnormally glycosylated polymeric IgA1, were detected in the serum of patients with advanced alcoholic cirrhosis. Moreover, aberrant IgA1 formed complexes with IgG and soluble CD89 in serum of patients with advanced alcoholic cirrhosis, similar to those found in primary IgAN. The IgA1 of alcoholic cirrhosis, however, had a modified N-glycosylation, not found in primary IgAN. In patients with alcoholic cirrhosis and IgAN, IgA deposits were associated with CD71 overexpression in mesangial areas, suggesting that CD71 might be involved in deposit formation. Although the IgA1 found in alcoholic cirrhosis bound more extensively to human mesangial cells than control IgA1, they differ from primary IgAN by not inducing mesangial cell proliferation. Thus, abnormally glycosylated IgA1 and soluble CD89-IgA and IgA-IgG complexes, features of primary IgAN, are also present in alcoholic cirrhosis. Hence, common mechanisms appear to be shared by diseases of distinct origins, indicating that common environmental factors may influence the development of IgAN.
authors.affiliation: Inserm U699, Paris, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Tissandié
authors.forename: Willy
authors.initials: W
authors.lastname: Morelle
authors.forename: Laureline
authors.initials: L
authors.lastname: Berthelot
authors.forename: François
authors.initials: F
authors.lastname: Vrtovsnik
authors.forename: Eric
authors.initials: E
authors.lastname: Daugas
authors.forename: Francine
authors.initials: F
authors.lastname: Walker
authors.forename: Didier
authors.initials: D
authors.lastname: Lebrec
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Trawalé
authors.forename: Claire
authors.initials: C
authors.lastname: Francoz
authors.forename: François
authors.initials: F
authors.lastname: Durand
authors.forename: Ivan C
authors.initials: IC
authors.lastname: Moura
authors.forename: Valérie
authors.initials: V
authors.lastname: Paradis
authors.forename: Richard
authors.initials: R
authors.lastname: Moreau
authors.forename: Renato C
authors.initials: RC
authors.lastname: Monteiro
mesh_terms: D000328:Adult; D000368:Aged; D000936:Antigen-Antibody Complex; D015703:Antigens, CD / Q000097:blood*; D001706:Biopsy; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D005690:Galactose / Q000097:blood / Q000172:deficiency; D005922:Glomerulonephritis, IGA / Q000097:blood / Q000276:immunology* / Q000473:pathology; D006031:Glycosylation; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood*; D007074:Immunoglobulin G / Q000097:blood*; D007668:Kidney / Q000276:immunology* / Q000473:pathology; D008104:Liver Cirrhosis, Alcoholic / Q000097:blood / Q000150:complications / Q000276:immunology* / Q000473:pathology; D008297:Male; D050527:Mesangial Cells / Q000276:immunology / Q000473:pathology; D008875:Middle Aged; D010297:Paris; D011961:Receptors, Fc / Q000097:blood*
chemical_list: D000936:Antigen-Antibody Complex; D015703:Antigens, CD; C036832:Fc(alpha) receptor; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D011961:Receptors, Fc; D005690:Galactose