Title

Tumor Necrosis Factor Receptor-Associated Factor 1 Influences Krn/I-A G7 Mouse Arthritis Autoantibody Production

Keywords

Arthritis; autoantibody; GPI; KRN; TRAF1KO

Abstract

Purpose: Recently, genomewide association analysis has revealed that the Tumor Necrosis Factor Receptor-associated factor 1-Complement 5 (TRAF1-C5) containing locus on chromosome 9 was associated with an increased risk for RA. Studies in model systems suggested that either gain- or loss-of-function TRAF1 mutations have immune effects that could plausibly lead to or exacerbate the arthritis phenotype. KRN/I-Ag7 (KxB/N) is a genetic mouse model of inflammatory arthritis. We aimed to assess the impact of TRAF1 deficiency on KRN/I-Ag7 mice. Methods: We have bred KRN/I-Ag7 mice onto a TRAF1-deficient background and followed cohorts for the spontaneous appearance of arthritis. We have also transferred KxB/N serum to B6.I-Ag7 TRAF1KO recipients. In addition, systemic autoimmunity was induced through cGVH by injecting bm12 splenocytes into TRAF1KO recipient mice. Results: TRAF1-deficient KRN/I-Ag7 mice spontaneously developed severe, progressive arthritis, comparable to that seen in TRAF1-intact KRN/I-A g7 mice. However, the anti-GPI antibody titer was significantly lower in the former group. Interestingly, the TRAF1KO mice that had background levels of anti-GPI antibodies still showed severe arthritis, although with a brief delay compared to TRAF1 sufficient mice. In addition, TRAF1KO mice were fully susceptible to passive, serum transfer experiments. In another model of autoimmunity, TRAF1KO had no effect on cGVH autoantibodies production; nor was the response to an exogenous antigen impaired. Conclusion: The pathogenesis of spontaneous KRN/I-Ag7 arthritis can largely proceed by TRAF1-independent pathways. The production of anti-GPI autoantibody, but not other autoantibody or antibody responses, was markedly impaired by TRAF1 deficiency. The spontaneous arthritis model in KRN mice appears to be much less antibody dependent than previously believed. © 2013 Springer Science+Business Media New York.

Publication Date

5-1-2013

Publication Title

Journal of Clinical Immunology

Volume

33

Issue

4

Number of Pages

759-766

Document Type

Article

Personal Identifier

scopus

DOI Link

https://doi.org/10.1007/s10875-013-9866-5

Socpus ID

84878020814 (Scopus)

Source API URL

https://api.elsevier.com/content/abstract/scopus_id/84878020814

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