Rheumatoid Arthritis: Flavell RA

Efthimiou P, Flavell RA, Furlan A, Gasbarrini G, Gava A, Koné-Paut I, Manna R, Punzi L, Sutterwala FS, Touitou I, Doria A. · Rheumatology Section, Lincoln Medical and Mental Health Center, New York, USA. · Clin Exp Rheumatol. · Pubmed #18570755 No free full text.

Abstract: The autoinflammatory syndromes are a group of disorders characterized by recurrent episodes of seemingly unprovoked inflammation without significant levels of autoantobodies and antigen specific T cells. Although a direct association between defective innate immune responses to bacterial components and these diseases has not been formally established, much ongoing research is aimed towards confirmation of that hypothesis. This article will review recent advances in the study of a subset of NOD-like receptors (NLRs), which control the activation of caspase-1 through the assembly of a large protein complex called inflammasome. Moreover, we will review recent progresses in understanding of a range of autoinflammatory conditions in humans.

Eynon EE, Flavell RA. · Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut, USA. · Immunol Rev. · Pubmed #10450503 No free full text.

Abstract: In the investigation of human disease, molecular biology has provided immunologists with several enormously powerful tools. Transgenic and knockout mice provide animal models to investigate mechanisms, as well as aid in the design of therapies for these diseases. These mice have been useful in several different ways. First, as direct models of disease they provide direct tools for the study of the disease. Second, expression of individual molecules can be altered in the context of established disease models. We describe here some of the models in use as well as the limitations and promise of this research.

Magnarelli LA, Ijdo JW, Padula SJ, Flavell RA, Fikrig E. · Department of Entomology, The Connecticut Agricultural Experiment Station, New Haven, Connecticut 06504, USA. · J Clin Microbiol. · Pubmed #10790090 links to  free full text

Abstract: Class-specific enzyme-linked immunosorbent assays (ELISAs) with purified recombinant antigens of Borrelia burgdorferi sensu stricto and Western blot analyses with whole cells of this spirochete were used to test human sera to determine which antigens were diagnostically important. In analyses for immunoglobulin M (IgM) antibodies, 14 (82%) of 17 serum samples from persons who had erythema migrans reacted positively by an ELISA with one or more recombinant antigens. There was frequent antibody reactivity to protein 41-G (p41-G), outer surface protein C (OspC), and OspF antigens. In an ELISA for IgG antibodies, 13 (87%) of 15 serum samples had antibodies to recombinant antigens; reactivity to p22, p39, p41-G, OspC, and OspF antigens was frequent. By both ELISAs, serum specimens positive for OspB, OspE, and p37 were uncommon. Analyses of sera obtained from persons who were suspected of having human granulocytic ehrlichiosis (HGE) but who lacked antibodies to ehrlichiae revealed IgM antibodies to all recombinant antigens of B. burgdorferi except OspB and IgG antibodies to all antigens except OspE. Immunoblotting of sera from the study group of individuals suspected of having HGE reaffirmed antibody reactivity to multiple antigens of B. burgdorferi. There was minor cross-reactivity when sera from healthy subjects or persons who had syphilis, oral infections, or rheumatoid arthritis were tested by ELISAs with p37, p41-G, OspB, OspC, OspE, and OspF antigens. Although the results of class-specific ELISAs with recombinant antigens were comparable to those recorded for assays with whole-cell antigen and for individuals with confirmed clinical diagnoses of Lyme borreliosis, immunoblotting is still advised as an adjunct procedure, particularly when there are low antibody titers by an ELISA.

Nurieva RI, Treuting P, Duong J, Flavell RA, Dong C. · Department of Immunology, and. Department of Comparative Medicine, University of Washington School of Medicine, Seattle, Washington, USA. · J Clin Invest. · Pubmed #12618524 links to  free full text

Abstract: CD4(+) helper Th cells play a major role in the pathogenesis of rheumatoid arthritis. Th cell activation, differentiation, and immune function are regulated by costimulatory molecules. Inducible costimulator (ICOS) is a novel costimulatory receptor expressed on activated T cells. We, as well as others, recently demonstrated its importance in Th2 cytokine expression and Ab class switching by B cells. In this study, we examined the role of ICOS in rheumatoid arthritis using a collagen-induced arthritis model. We found that ICOS knockout mice on the DBA/1 background were completely resistant to collagen-induced arthritis and exhibited absence of joint tissue inflammation. These mice, when immunized with collagen, exhibited reduced anti-collagen IgM Ab's in the initial stage and IgG2a Ab's at the effector phase of collagen-induced arthritis. Furthermore, ICOS regulates the in vitro and in vivo expression of IL-17, a proinflammatory cytokine implicated in rheumatoid arthritis. These data indicate that ICOS is essential for collagen-induced arthritis and may suggest novel means for treating patients with rheumatoid arthritis.