HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Adarichev, V. A. Articles by Glant, T. T. Search for Related Content PubMed PubMed Citation Articles by Adarichev, V. A. Articles by Glant, T. T.

Combined Autoimmune Models of Arthritis Reveal Shared and Independent Qualitative (Binary) and Quantitative Trait Loci ¹

Vyacheslav A. Adarichev^*, Juan C. Valdez^2,*, Tamás Bárdos^3,*, Alison Finnegan^,, Katalin Mikecz^*, and Tibor T. Glant^4,*,

^* Section of Biochemistry and Molecular Biology, Departments of Orthopedic Surgery and Biochemistry, Section of Rheumatology, Department of Internal Medicine, and Department of Immunology/Microbiology, Rush University at Rush-Presbyterian-St. Luke’s Medical Center, Chicago, IL 60612

Collagen-induced arthritis (CIA) and proteoglycan-induced arthritis (PGIA) are murine models for rheumatoid arthritis both in terms of their pathology and genetics. Using the F₂ hybrids of the CIA-susceptible, but PGIA-resistant DBA/1 mice, and the CIA-resistant, but PGIA-susceptible BALB/c mice, our goals were to 1) identify both model-specific and shared loci that confer disease susceptibility, 2) determine whether any pathophysiological parameters could be used as markers that distinguish between nonarthritic and arthritic mice, and 3) analyze whether any immune subtraits showed colocalization with arthritis-related loci. To identify chromosomal loci, we performed a genome scan on 939 F₂ hybrid mice. For pathophysiological analyses, we measured pro- and anti-inflammatory cytokines (IL-1, IL-6, TNF-, IFN-, IL-4, IL-10, IL-12), Ag-specific T cell proliferation and IL-2 production, serum IgG1 and IgG2 levels of both auto- and heteroantibodies, and soluble CD44. In addition to multiple CIA- and PGIA-related loci identified in previous studies, we have identified nine new CIA- and eight new PGIA-linked loci. Comprehensive statistical analysis demonstrated that IL-2 production, T cell proliferation, and IFN- levels differed significantly between arthritic and nonarthritic animals in both CIA and PGIA populations. High levels of TNF-, IFN-, IL-2, and Ab production were detected in F₂ hybrids with CIA, whereas T cell proliferation, IL-2 and IFN- production, and a shift to IgG2a isotype were more characteristic of PGIA. Quantitative trait loci analysis demonstrated colocalization of numerous immune subtraits with arthritis-related traits. Quantitative trait loci on chromosomes 5, 10, 17, 18, and X were found to control arthritis in both models.

This article has been cited by other articles:

				T. T. Glant, S. Szanto, A. Vegvari, Z. Szabo, K. Kis-Toth, K. Mikecz, and V. A. Adarichev Two Loci on Chromosome 15 Control Experimentally Induced Arthritis through the Differential Regulation of IL-6 and Lymphocyte Proliferation J. Immunol., July 15, 2008; 181(2): 1307 - 1314. [Abstract] [Full Text] [PDF]

				X. Yu, K. Bauer, P. Wernhoff, D. Koczan, S. Moller, H.-J. Thiesen, and S. M. Ibrahim Fine Mapping of Collagen-Induced Arthritis Quantitative Trait Loci in an Advanced Intercross Line J. Immunol., November 15, 2006; 177(10): 7042 - 7049. [Abstract] [Full Text] [PDF]

				B. Sarraj, K. Ludanyi, T. T. Glant, A. Finnegan, and K. Mikecz Expression of CD44 and L-Selectin in the Innate Immune System Is Required for Severe Joint Inflammation in the Proteoglycan-Induced Murine Model of Rheumatoid Arthritis J. Immunol., August 1, 2006; 177(3): 1932 - 1940. [Abstract] [Full Text] [PDF]

				K. Ohmura, A. Johnsen, A. Ortiz-Lopez, P. Desany, M. Roy, W. Besse, J. Rogus, M. Bogue, A. Puech, M. Lathrop, et al. Variation in IL-1{beta} gene expression is a major determinant of genetic differences in arthritis aggressivity in mice PNAS, August 30, 2005; 102(35): 12489 - 12494. [Abstract] [Full Text] [PDF]

				A. Vegvari, Z. Szabo, S. Szanto, A. B. Nesterovitch, K. Mikecz, T. T. Glant, and V. A. Adarichev Two Major Interacting Chromosome Loci Control Disease Susceptibility in Murine Model of Spondyloarthropathy J. Immunol., August 15, 2005; 175(4): 2475 - 2483. [Abstract] [Full Text] [PDF]

				L. I. Rutitzky, H. J. Hernandez, Y.-S. Yim, D. E. Ricklan, E. Finger, C. Mohan, I. Peter, E. K. Wakeland, and M. J. Stadecker Enhanced Egg-Induced Immunopathology Correlates With High IFN-{gamma} in Murine Schistosomiasis: Identification of Two Epistatic Genetic Intervals J. Immunol., January 1, 2005; 174(1): 435 - 440. [Abstract] [Full Text] [PDF]

				S. Szanto, I. Gal, A. Gonda, T. T. Glant, and K. Mikecz Expression of L-Selectin, but Not CD44, Is Required for Early Neutrophil Extravasation in Antigen-Induced Arthritis J. Immunol., June 1, 2004; 172(11): 6723 - 6734. [Abstract] [Full Text] [PDF]

				R. J. A. Fijneman, M. Vos, J. Berkhof, P. Demant, and G. Kraal Genetic Analysis of Macrophage Characteristics as a Tool to Identify Tumor Susceptibility Genes: Mapping of Three Macrophage-Associated Risk Inflammatory Factors, Marif1, Marif2, and Marif3 Cancer Res., May 15, 2004; 64(10): 3458 - 3464. [Abstract] [Full Text] [PDF]