Congenic strains displaying similar clinical phenotype of arthritis represent different immunologic models of inflammation.
Proteoglycan (PG)-induced arthritis (PGIA) is an autoimmune inflammatory disease controlled by multiple genes in the murine genome. BALB/c x 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-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha) 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-gamma 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.
Adarichev
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VA
Section of Molecular Medicine, Department of Orthopedic Surgery, Rush University Medical Center, Chicago, IL 60612, USA.
Vegvari
A
A
Szabo
Z
Z
Kis-Toth
K
K
Mikecz
K
K
Glant
T T
TT
D000818:Animals; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000235:genetics* / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology / Q000473:pathology; D003433:Crosses, Genetic; D005260:Female; D018836:Inflammation Mediators / Q000633:toxicity; D008297:Male; D051379:Mice; D020297:Mice, Congenic; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D018448:Models, Immunological; D010641:Phenotype; D011509:Proteoglycans / Q000633:toxicity
D018836:Inflammation Mediators; D011509:Proteoglycans