title: Recombinant Salmonella typhimurium outer membrane protein A is recognized by synovial fluid CD8 cells and stimulates synovial fluid mononuclear cells to produce interleukin (IL)-17/IL-23 in patients with reactive arthritis and undifferentiated spondyloarthropathy.
abstract: In developing countries, one-third of patients with reactive arthritis (ReA) and undifferentiated spondyloarthropathy (uSpA) are triggered by Salmonella typhimurium. Synovial fluid mononuclear cells (SFMCs) of patients with ReA and uSpA proliferate to low molecular weight fractions (lmwf) of outer membrane proteins (Omp) of S. typhimurium. To characterize further the immunity of Omp of Salmonella, cellular immune response to two recombinant proteins of lmwf, OmpA and OmpD of S. typhimurium (rOmpA/D-sal) was assessed in 30 patients with ReA/uSpA. Using flow cytometry, 17 of 30 patients' SF CD8(+) T cells showed significant intracellular interferon (IFN)-γ to Omp crude lysate of S. typhimurium. Of these 17, 11 showed significantly more CD8(+) CD69(+) IFN-γ T cells to rOmpA-sal, whereas only four showed reactivity to rOmpD-sal. The mean stimulation index was significantly greater in rOmpA-sal than rOmpD-sal [3·0 (1·5-6·5) versus 1·5 (1·0-2·75), P < 0·005]. Similarly, using enzyme-linked immunospot (ELISPOT) in these 17 patients, the mean spots of IFN-γ-producing SFMCs were significantly greater in rOmpA-sal than rOmpD-sal [44·9 (3·5-130·7) versus 19·25 (6-41), P < 0·05]. SFMCs stimulated by rOmpA-sal produced significantly more proinflammatory cytokines than rOmpD-sal: IFN-γ [1·44 (0·39-20·42) versus 0·72 (0·048-9·15) ng/ml, P < 0·05], interleukin (IL)-17 [28·60 (6·15-510·86) versus 11·84 (6·83-252·62) pg/ml, P < 0·05], IL-23 [70·19 (15-1161·16) versus 28·25 (> 15-241·52) pg/ml, P < 0·05] and IL-6 [59·78 (2·03-273·36) versus 10·17 (0·004-190·19) ng/ml, P < 0·05]. The rOmpA-sal-specific CD8(+) T cell response correlated with duration of current synovitis (r = 0·53, P < 0·05). Thus, OmpA of S. typhimurium is a target of SF CD8(+) T cells and drives SFMC to produce increased cytokines of the IL-17/IL-23 axis which contribute to the pathogenesis of Salmonella-triggered ReA.
authors.affiliation: Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences.
authors.forename: S
authors.initials: S
authors.lastname: Chaurasia
authors.affiliation: Biotechnology Division, Central Institute of Medicinal and Aromatic Plants, Lucknow, India.
authors.forename: A K
authors.initials: AK
authors.lastname: Shasany
authors.affiliation: Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences.
authors.forename: A
authors.initials: A
authors.lastname: Aggarwal
authors.affiliation: Department of Clinical Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences.
authors.forename: R
authors.initials: R
authors.lastname: Misra
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016918:Arthritis, Reactive / Q000276:immunology* / Q000382:microbiology / Q000503:physiopathology; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D020381:Interleukin-17 / Q000096:biosynthesis* / Q000276:immunology; D053759:Interleukin-23 / Q000096:biosynthesis*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D008297:Male; D008875:Middle Aged; D000091402:Prohibitins; D012480:Salmonella Infections / Q000276:immunology; D012486:Salmonella typhimurium / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D025242:Spondylarthropathies / Q000276:immunology*; D013582:Synovial Fluid / Q000166:cytology / Q000276:immunology*; D055815:Young Adult
chemical_list: D001425:Bacterial Outer Membrane Proteins; D016207:Cytokines; C508717:IL17A protein, human; D020381:Interleukin-17; D053759:Interleukin-23; C000717331:PHB2 protein, human; D000091402:Prohibitins; C078167:OMPA outer membrane proteins; D007371:Interferon-gamma
keywords: antigens; arthritis; bacterial; cytokines; cytotoxic T cells