title: Peculiar antibody reactivity to human connexin 37 and its microbial mimics in patients with Crohn's disease.
abstract: OBJECTIVE
  We found that pooled Crohn's disease (CD) sera strongly react with a human gap-junction connexin 37 (Cx37) peptide and tested for anti-Cx37 antibody reactivity in sera from CD patients and controls. We also investigated whether peptide-recognition is due to Cx37/microbial molecular mimicry.
  
  
  METHODS
  The PSI-BLAST program was used for Cx37(121-135)/microbial alignment. Reactivity to biotinylated human Cx37(121-135) and its microbial mimics was determined by ELISA using sera from 44 CD, 30 ulcerative colitis and 28 healthy individuals.
  
  
  RESULTS
  Anti-Cx37(121-135) reactivity (1/200 dilution) was present in 30/44 (68%) CD cases and persisted at 1/1000 dilution. Database search shows that Cx37(121-135) contains the -ALTAV- motif which is cross-recognized by diabetes-specific phogrin and enteroviral immunity. Testing of 9 Cx37(121-135)-microbial mimics revealed 57-68% reactivity against human enterovirus C, Lactococcus lactis, coxsackie virus A24 and B4. Anti-Cx37(121-135) was inhibited by itself or the microbial mimics. No reactivity was found against the poliovirus, rubella, and Mycobacterium tuberculosis mimics, or the beta cell phogrin autoantigen. Microbial/Cx37 reactivity was not able to differentiate CD patients from UC or healthy controls, in terms of overall prevalence and antibody titres, but microbial mimics were unable to inhibit reactivity to human Cx37 in the majority of the controls.
  
  
  CONCLUSIONS
  Sera from CD patients react with connexin 37 and cross-react with specific Cx37-mimicking enteroviral peptides. Microbial/self reactivity can be seen in UC and healthy controls. The lack of responses to other Cx37(121-135) microbial mimics and the inability of the reactive microbes to inhibit reactivity to self is intriguing and warrants further investigation.
authors: Division of Gene and Cell Based Therapy, King's College London School of Medicine at King's College Hospital, London, UK.
authors: Andreas
authors: A
authors: Koutsoumpas
authors: Dimitrios
authors: D
authors: Polymeros
authors: Zacharias
authors: Z
authors: Tsiamoulos
authors: Daniel
authors: D
authors: Smyk
authors: George
authors: G
authors: Karamanolis
authors: Konstantinos
authors: K
authors: Triantafyllou
authors: E I
authors: EI
authors: Rigopoulou
authors: Alastair
authors: A
authors: Forbes
authors: Diego
authors: D
authors: Vergani
authors: Dimitrios P
authors: DP
authors: Bogdanos
authors: Spiros D
authors: SD
authors: Ladas
mesh_terms: D000328:Adult; D000937:Antigen-Antibody Reactions; D001426:Bacterial Proteins / Q000737:chemistry / Q000276:immunology; D017630:Connexins / Q000097:blood / Q000737:chemistry / Q000276:immunology*; D003424:Crohn Disease / Q000097:blood / Q000276:immunology* / Q000382:microbiology; D029822:Enterovirus B, Human / Q000737:chemistry; D030015:Enterovirus C, Human / Q000737:chemistry; D005260:Female; D006801:Humans; D013294:Lactococcus lactis / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D018716:Molecular Mimicry / Q000276:immunology*; D017386:Sequence Homology, Amino Acid; D014764:Viral Proteins / Q000737:chemistry / Q000276:immunology; D000097006:Gap Junction alpha-4 Protein
chemical_list: D001426:Bacterial Proteins; D017630:Connexins; D014764:Viral Proteins; D000097006:Gap Junction alpha-4 Protein