In vitro-generated immune complexes containing galactose-deficient IgA1 stimulate proliferation of mesangial cells.
IgA nephropathy (IgAN) patients have elevated serum levels of immune complexes consisting of IgA1 with galactose-deficient hinge-regionO-glycans (Gd-IgA1) and anti-glycan IgG. These immune complexes deposit in the kidney and activate mesangial cells. To confirm that the activity of these immune complexes depends on the interaction of Gd-IgA1 with anti-glycan IgG, we generatedin vitroanalogous immune complexes using Gd-IgA1 myeloma protein and anti-glycan IgG from cord blood of healthy women. The Gd-IgA1 and anti-glycan IgG from cord-blood serum formed IgA1-IgG immune complexes that resembled those in sera of patients with IgAN. Furthermore, the ability to activate cellular proliferation was dependent on a heat-sensitive serum factor. In summary, we developed a new protocol forin-vitroformation of IgA1-IgG immune complexes, thus providing a new tool for studies of the pathogenesis of IgAN.
Department of Microbiology, University of Alabama, Birmingham, AL, USA ; Department of Pediatrics, Nippon Medical School, Tokyo, Japan.
Takeshi
T
Yanagihara
Rhubell
R
Brown
Stacy
S
Hall
Zina
Z
Moldoveanu
Alice
A
Goepfert
Milan
M
Tomana
Bruce A
BA
Julian
Jiri
J
Mestecky
Jan
J
Novak
Anti-glycan IgG; Galactose-deficient IgA1; IgA nephropathy; Immune complexes; Mesangial cells; O-glycosylation