Cross-reactivity between the rheumatoid arthritis-associated motif EQKRAA and structurally related sequences found in

H Tiwana1, C Wilson, A Alvarez

  • 1Infection and Immunity Group, King's College, London, United Kingdom.

Insights

Molecular mimicry between the bacterium Proteus mirabilis and rheumatoid arthritis (RA) susceptibility sequences may contribute to RA development. This study found specific bacterial peptides mimic sequences found in RA-associated HLA alleles.

Area of Science:

  • Immunology
  • Microbiology
  • Genetics

Background:

  • Rheumatoid arthritis (RA) pathogenesis may involve molecular mimicry.
  • Certain HLA-DRB1 alleles are associated with RA susceptibility.

Purpose of the Study:

  • To investigate potential molecular mimicry between RA susceptibility sequences and bacterial peptides.
  • To explore the role of Proteus mirabilis in RA etiopathogenesis.

Main Methods:

  • Antiserum-based binding assays were used to test cross-reactivity between peptides.
  • Peptide binding to cell lines expressing specific HLA-DRB1 alleles was assessed.

Main Results:

  • Antiserum against RA susceptibility sequence EQKRAA bound to bacterial peptide ESRRAL, and vice versa.
  • These specific peptides bound to HLA-DRB1*0401 (RA-associated) but not HLA-DRB1*0402 (not associated with RA).
  • Other related bacterial and self-peptide sequences showed no significant binding to the tested HLA alleles.

Conclusions:

  • Molecular mimicry between Proteus mirabilis and RA-associated HLA alleles is suggested as a potential mechanism in RA development.
  • This mimicry may involve specific bacterial peptides and RA-associated HLA variants.

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