title: The 19 kDa protein of Yersinia enterocolitica O:3 is recognized on the cellular and humoral level by patients with Yersinia induced reactive arthritis.
abstract: OBJECTIVE
  Gastrointestinal infections with Yersinia enterocolitica O:3 (YE O:3) can trigger reactive arthritis (ReA). The cellular immune response seems to be of pathogenic importance in ReA, since synovial fluid mononuclear cells (SFMC) of patients with ReA have been shown to recognize YE O:3 antigens. One of these, a 19 kDa protein identified as the beta-urease subunit of YE, has been identified as a target of SFMC. We investigated the humoral immune response to this antigen.
  
  
  METHODS
  Sera of 32 patients with SFMC proliferation to YE O:3 diagnosed as having ReA (n = 16) and undifferentiated oligoarthritis (UOA, n = 16), and of patients with other rheumatic diseases (n = 32) and healthy persons (n = 12) were investigated for the humoral response to the biochemically purified 19 kDa protein of YE. Anti-19 kDa antibodies (ab) were identified by immunoblotting; ab to the Yersinia outer membrane protein (YOP) antigen were detected by ELISA. Proliferation of SFMC to 19 kDa and other YE O:3 antigens was tested in 12 patients in parallel.
  
  
  RESULTS
  SFMC of all 32 patients with ReA and UOA showed the highest proliferation to YE O:3 (13.7+/-7.5), and 10/12 of these patients had the highest stimulation index to the 19 kDa (14.9+/-6.4). Anti-19 kDa IgG ab were detected in 93% and 55% and anti-19 kDa IgA ab in 56% and 36% of the ReA and UOA patients, respectively, compared to 26% (p = 0.002) and 8% (p = 0.001) in controls. IgG ab to the 19 kDa were sensitive (93%) and IgA ab specific (92%) to detect patients with a synovial cellular response to YE. IgG ab to YOP were found in 62% and IgA ab in 46% of the ReA patients and in 32% (p = 0.002) and 13% (p = 0.004) of the controls.
  
  
  CONCLUSIONS
  This study provides evidence of a cellular and a significant humoral immune response to the 19 kDa protein in Yersinia triggered arthritis. Detection of IgG antibodies to the 19 kDa correlates with a synovial cellular immune response in YE induced arthritis. These antibodies can be used as a screening system for research and possibly also for clinical purposes, since absence of such antibodies seems to negatively predict YE O:3 directed immune reactivity.
authors.affiliation: Department of Nephrology and Rheumatology, Klinikum Benjamin Franklin, Freie Universität Berlin, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Appel
authors.forename: A
authors.initials: A
authors.lastname: Mertz
authors.forename: A
authors.initials: A
authors.lastname: Distler
authors.forename: J
authors.initials: J
authors.lastname: Sieper
authors.forename: J
authors.initials: J
authors.lastname: Braun
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000917:Antibody Formation; D000937:Antigen-Antibody Reactions; D000942:Antigens, Bacterial / Q000276:immunology*; D001168:Arthritis / Q000276:immunology; D016918:Arthritis, Reactive / Q000175:diagnosis / Q000276:immunology*; D015415:Biomarkers / Q000032:analysis; D015153:Blotting, Western; D002648:Child; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D007111:Immunity, Cellular / Q000502:physiology; D007070:Immunoglobulin A / Q000032:analysis; D007074:Immunoglobulin G / Q000032:analysis; D008297:Male; D008875:Middle Aged; D000091402:Prohibitins; D012680:Sensitivity and Specificity; D015009:Yersinia Infections / Q000175:diagnosis / Q000276:immunology*; D015008:Yersinia enterocolitica / Q000276:immunology*
chemical_list: D000942:Antigens, Bacterial; D015415:Biomarkers; D007070:Immunoglobulin A; D007074:Immunoglobulin G; C000717331:PHB2 protein, human; D000091402:Prohibitins