Genetic control of antibody production during collagen-induced arthritis development in heterogeneous stock mice
(2012) In Arthritis and Rheumatism 64(11). p.3594-3603- Abstract
- 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... (More)
- 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. (Less)
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- author
- organization
- publishing date
- 2012
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Arthritis and Rheumatism
- volume
- 64
- issue
- 11
- pages
- 3594 - 3603
- publisher
- John Wiley & Sons Inc.
- external identifiers
-
- wos:000310544500013
- scopus:84868104226
- pmid:22886420
- ISSN
- 1529-0131
- DOI
- 10.1002/art.34658
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Medical Inflammation Research (013212019)
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- aa5edcd9-4c53-4fa3-a7fb-c1775ba611e7 (old id 3283464)
- date added to LUP
- 2016-04-01 10:56:59
- date last changed
- 2022-03-20 01:32:35
@article{aa5edcd9-4c53-4fa3-a7fb-c1775ba611e7, abstract = {{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.}}, author = {{Forster, Michael and Raposo, Bruno and Ekman, Diana and Klaczkowska, Dorota and Popovic, Marjan and Nandakumar, Kutty S. and Lindvall, Therese and Hultqvist, Malin and Teneva, Ivanka and Johannesson, Martina and Ahlqvist, Emma and Holmdahl, Rikard}}, issn = {{1529-0131}}, language = {{eng}}, number = {{11}}, pages = {{3594--3603}}, publisher = {{John Wiley & Sons Inc.}}, series = {{Arthritis and Rheumatism}}, title = {{Genetic control of antibody production during collagen-induced arthritis development in heterogeneous stock mice}}, url = {{http://dx.doi.org/10.1002/art.34658}}, doi = {{10.1002/art.34658}}, volume = {{64}}, year = {{2012}}, }