Cytokine and HLA polymorphisms in atrophic gastritis: Relevance in the onset of autoimmunity against gastric and thyroid cells

M. Asti, E. Trespi, C. Colla, C. Alvisi, M. Perego, A. De Silvestri, C. Badulli, L. Salvaneschi, M. Martinetti

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Abstract

Helicobacter pylori (HP), a Gram negative gastric pathogen, plays the major causative role in the atrophic gastritis, which has always been considered an autoimmune disease. In the present work we wanted to investigate the role of cytokine and HLA polymorphisms in the outcome of HP-induced gastric disease. In particular we speculated the possibility that a susceptible genetic profile could influence the evolution of infection towards autoimmune gastritis and/or thyroiditis. We enrolled 43 patients: 15 were HP positive at level of gastric biopsy, 16 had anti-parietal cells autoantibodies (APCA) and 14 had autoantibodies against thyroid. All subjects were genomically typed for HLA class I and II alleles, at four digits, and tested for cytokine polymorphisms of TNFA (-308 promoter), TGFβ1 (codon 10 and 25), IL-10 (promoter -1082, -819 and -592), IL-6 (promoter -174) and IFN-γ (intron 1 +874) using PCR-SSP technique. We observed a direct relationship between APCA autoantibodies and biopsy proven HP clearance (p=0.0012). Correspondence analysis showed that patients with APCA autoantibodies have the following low producer genotypes of IL-6 and TGF-β1: IL-6 -174 CC and TGF-β1 10CC and/or TGF-β1 25 CC. Autoimmunity against thyroid gland was instead related to the presence of HLA-DRB1*0301 allele (p=0.012). Correspondence analysis showed that patients with anti-thyroid autoantibodies displayed the "high producer" genotypes of IFN-γ, IL-10 and TNFA: IFN-γ +874 TT; IL-10-819 CC and -592 CC; TNFA-308 A. We applied multiple logistic regression to evaluate the hierarchy risk of autoimmunity in patients affected by atrophic gastritis. We found that the strongest association was with HP disappearance (OR 14.8, p=0.0092), followed by the presence of HLA-DRB1 *0301 (OR 2.29) and IFN-γ +874 TT high producer genotype (OR 1.78). We hypothesised that, in people possessing peculiar HLA or cytokine polymorphisms, HP infection could induce autoimmune gastritis and/or thyroiditis as the result of cellular or humoral aberrant reaction against self structures through molecular mimicry between bacterial antigen and gastric or thyroid constituents.

Original languageEnglish
Pages (from-to)237
Number of pages1
JournalEuropean Journal of Immunogenetics
Volume28
Issue number2
Publication statusPublished - 2001

ASJC Scopus subject areas

  • Immunology
  • Genetics

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    Asti, M., Trespi, E., Colla, C., Alvisi, C., Perego, M., De Silvestri, A., Badulli, C., Salvaneschi, L., & Martinetti, M. (2001). Cytokine and HLA polymorphisms in atrophic gastritis: Relevance in the onset of autoimmunity against gastric and thyroid cells. European Journal of Immunogenetics, 28(2), 237.