IgG Fc receptor polymorphisms and association with autoimmune disease.
The aim of this study was to investigate whether a genetic polymorphism of Fc gammaRIII exists in mice, which could explain the different susceptibility to pathogenic IgG anti-collagen type II (CII) antibodies in mice carrying the collagen-induced arthritis (CIA)-susceptible H-2q haplotype. The gene for Fc gammaRIII was sequenced in 11 common mouse strains, and the results revealed three different haplotypes of mouse Fc gammaRIII: Fc gammaRIII:V, Fc gammaRIII:H and Fc gammaRIII:T. To study the consequences of this polymorphism, we generated mice carrying the Fc gammaRIII:H haplotype from the CIA-susceptible, H-2q-positive DBA/1 mouse or the Fc gammaRIII:V haplotype from the CIA-resistant, H-2q-positive SWR mouse. After CII immunization or transfer of IgG anti-CII antibodies, Fc gammaRIII:H-expressing mice, but not Fc gammaRIII:V-expressing mice, developed progressively severe arthritis. We also investigated if C5, in addition to Fc gammaRIII polymorphism, could affect the susceptibility to the pathogenic IgG anti-CII antibodies in H-2q-positive mice. Here we show that SWR mice, naturally deficient in C5, can develop CIA when supplemented with C5 and that anti-C5 antibody treatment of Fc gammaRIII:H-expressing mice inhibits arthritis development. These data demonstrate for the first time a genetic polymorphism of Fc gammaRIII in mice that may, together with C5, regulate induction of autoimmune disease.
Andrén
Maria
M
Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden.
Johanneson
Bo
B
Alarcón-Riquelme
Marta E
ME
Kleinau
Sandra
S
D000595:Amino Acid Sequence; D000818:Animals; D001169:Arthritis, Experimental / Q000235:genetics* / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology*; D001483:Base Sequence; D003182:Complement C5 / Q000172:deficiency / Q000276:immunology; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D017452:Receptors, IgG / Q000235:genetics*
D003182:Complement C5; D017452:Receptors, IgG