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Genetic control of antibody production during collagen-induced arthritis development in heterogeneous stock mice

In English

Författare

  • Michael Forster
  • Bruno Raposo
  • Diana Ekman
  • Dorota Klaczkowska
  • Marjan Popovic
  • Kutty S. Nandakumar
  • Therese Lindvall
  • Malin Hultqvist
  • Ivanka Teneva
  • Martina Johannesson
  • Emma Ahlqvist
  • Rikard Holmdahl
Visa allt

Summary, in English

Objective. To identify genetic factors driving pathogenic autoantibody formation in collagen-induced arthritis (CIA), a mouse model of rheumatoid arthritis (RA), in order to better understand the etiology of RA and identify possible new avenues for therapeutic intervention. Methods. We performed a genome-wide analysis of quantitative trait loci controlling autoantibody to type II collagen (anti-CII), anti-citrullinated protein antibody (ACPA), and rheumatoid factor (RF). To identify loci controlling autoantibody production, we induced CIA in a heterogeneous stock-derived mouse cohort, with contribution of 8 inbred mouse strains backcrossed to C57BL/10. Q. Serum samples were collected from 1,640 mice before arthritis onset and at the peak of the disease. Antibody concentrations were measured by standard enzyme-linked immunosorbent assay, and linkage analysis was performed using a linear regression-based method. Results. We identified loci controlling formation of anti-CII of different IgG isotypes (IgG1, IgG3), antibodies to major CII epitopes (C1, J1, U1), antibodies to a citrullinated CII peptide (citC1), and RF. The anti-CII, ACPA, and RF responses were all found to be controlled by distinct genes, one of the most important loci being the immunoglobulin heavy chain locus. Conclusion. This comprehensive genetic analysis of autoantibody formation in CIA demonstrates an association not only of anti-CII, but interestingly also of ACPA and RF, with arthritis development in mice. These results underscore the importance of non-major histocompatibility complex genes in controlling the formation of clinically relevant autoantibodies.

Avdelning/ar

  • Immunology

Publiceringsår

2012

Språk

Engelska

Sidor

3594-3603

Publikation/Tidskrift/Serie

Arthritis and Rheumatism

Volym

64

Issue

11

Dokumenttyp

Artikel i tidskrift

Förlag

John Wiley & Sons Inc.

Ämne

  • Rheumatology and Autoimmunity

Status

Published

Forskningsgrupp

  • Immunology

ISBN/ISSN/Övrigt

  • ISSN: 1529-0131