Genetic control of antibody production during collagen induced arthritis development in heterogeneous stock mice (171.44)

• Published in: JOURNAL OF IMMUNOLOGY Vol. 188; no. 1_Supplement; pp. 171 - 171.44
• Main Authors: Foerster, Michael, Raposo, Bruno, Ekman, Diana, Klaczkowska, Dorota, Popovic, Marjan, Kutty Selva, Nandakumar, Lindvall, Therese, Hultqvist, Malin, Teneva, Ivanka, Johannesson, Martina, Ahlqvist, Emma, Holmdahl, Rikard
• Format: Journal Article Conference Proceeding
• Language: English
• Published: 01-05-2012
• Subjects: Medicin och hälsovetenskap
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.188.Supp.171.44

The aim of this study was to identify genetic factors driving pathogenic autoantibody formation in collagen induced arthritis (CIA), a mouse model for rheumatoid arthritis (RA) in order to understand the etiology of the disease and improve possibilities for therapeutic intervention. To this end we made a genome wide analysis of quantitative trait loci (QTL) controlling autoantibodies towards type II collagen (AC2A), anti-citrullinated protein antibodies (ACPA) and rheumatoid factors (RF). To identify loci controlling autoantibody production, we induced CIA in a heterogeneous stock (HS) derived mouse cohort. Serum samples of 1843 mice were collected before onset and at peak of the disease. All antibody concentrations were measured by ELISA and linkage analysis was performed using a linear regression based method. We identified loci controlling formation of AC2A of different IgG isotypes, antibodies to major type II collagen (CII) epitopes, to a citrullinated CII peptide and RF. The AC2A, ACPA and RF responses were all found to be controlled by distinct genes, one of the most important loci being the Immunoglobulin heavy chain (IgH) locus. Here, we provide a comprehensive genetic analysis of autoantibody formation in CIA. Our study demonstrates that not only AC2A, but interestingly also ACPA and RF are associated with arthritis development in mice. These results underscore the importance of non-MHC genes controlling the formation of clinically relevant autoantibodies.