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Congenic strains displaying similar clinical phenotype of arthritis represent different immunologic models of inflammation

Genes & Immunity volume 9, pages 591–601 (2008)Cite this article

Abstract

Proteoglycan (PG)-induced arthritis (PGIA) is an autoimmune inflammatory disease controlled by multiple genes in the murine genome. BALB/c × DBA/2 congenic strains carrying four major PGIA chromosome loci were immunized, and positions of loci on chromosomes 3, 7, 8 and 19 (loci Pgia26, Pgia21, Pgia4 and Pgia12, respectively) were confirmed. Each congenic strain exhibited a different pattern of regulation of clinical and immunologic features of PGIA, and these features were significantly influenced by gender. Locus Pgia26 delayed PGIA onset in males and females, and the effect was associated with a lower rate of antigen-induced lymphocyte proliferation and lower production of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α) and interleukin-4 (IL-4). Pgia12 similarly delayed onset in males, but the effect was achieved by elevated proliferation of PG-specific lymphocytes and enhanced production of IFN-γ and IL-4. The effect of the Pgia21 locus was arthritis-suppressive in females but PGIA-permissive in congenic males. These opposite effects are attributed to two-fold higher serum autoantibody and IL-6 levels in males than in females. Our study supports the idea that each congenic strain represents a different immunologic subtype of PGIA, providing an explanation for the complex etiology and various clinical phenotypes of rheumatoid arthritis.

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Acknowledgements

This work was supported by research Grants P01 AR045652 and R01 AR040310 of the National Institutes of Health (USA), the JO Galante, MD Endowment Chair (Rush University Medical Center, Chicago, IL, USA) and The Grainger Foundation (Chicago, IL, USA). We thank for human cartilage samples received from surgeons of Midwest Orthopedics (Rush University Medical Center, Chicago, IL, USA) and technical support of Dr A Nesterovitch and Dr G Hutas (Rush University Medical Center).

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Author notes

  1. V A Adarichev

    Present address: 4Current address: Department of Medicine, The Division of Rheumatology, Albert Einstein College of Medicine of Yeshiva University, Bronx, NY, USA.,

Authors and Affiliations

  1. Department of Orthopedic Surgery, Section of Molecular Medicine, Rush University Medical Center, Chicago, IL, USA

    V A Adarichev, A Vegvari, Z Szabo, K Kis-Toth, K Mikecz & T T Glant

  2. Department of Biochemistry, Rush University Medical Center, Chicago, IL, USA

    K Mikecz & T T Glant

  3. Department of Internal Medicine, Section of Rheumatology, Rush University Medical Center, Chicago, IL, USA

    T T Glant

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  1. V A Adarichev
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Correspondence to T T Glant.

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Adarichev, V., Vegvari, A., Szabo, Z. et al. Congenic strains displaying similar clinical phenotype of arthritis represent different immunologic models of inflammation. Genes Immun 9, 591–601 (2008). https://doi.org/10.1038/gene.2008.54

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