Autoimmune Mechanisms in Antibiotic Treatment-Resistant Lyme Arthritis

J Autoimmun. 2001 May;16(3):263-8. doi: 10.1006/jaut.2000.0495.

Abstract

In about 10% of patients with Lyme arthritis in the United States, joint inflammation persists for months or even several years after the apparent eradication of the spirochete, Borrelia burgdorferi, from the joint with antibiotic treatment. We propose a model of molecular mimicry affecting genetically susceptible individuals to explain this treatment-resistant course. The majority of patients with treatment-resistant Lyme arthritis have HLA-DRB1*0401 or related alleles, and the severity and duration of their arthritis correlate with cellular and humoral immune responses to outer-surface protein A OspA) of the spirochete. Using an algorithm, the immunodominant epitope of OspA presented by the DRB1*0401 molecule was predicted to be located at aa 165-173. In a search of the Genetics Computer Group gene bank, only one human protein was identified, lymphocyte function associated antigen-1 (hLFA-1), that had sequence homology with OspA(165-173)and predicted binding in the DRB1*0401 molecule. Synovial fluid T cells from most patients with treatment-resistant arthritis responded to both OspA and hLFA-1, whereas those from patients with other forms of chronic inflammatory arthritis did not. Molecular mimicry between a dominant T cell epitope of OspA and hLFA-1 may be an important factor in the persistence of joint inflammation in genetically susceptible patients with treatment-resistant Lyme arthritis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Anti-Bacterial Agents / therapeutic use*
  • Antigens, Surface / genetics
  • Antigens, Surface / immunology
  • Arthritis, Infectious / drug therapy
  • Arthritis, Infectious / immunology*
  • Arthritis, Infectious / microbiology
  • Arthritis, Infectious / physiopathology
  • Autoantigens / immunology
  • Autoimmunity / immunology*
  • Bacterial Outer Membrane Proteins / genetics
  • Bacterial Outer Membrane Proteins / immunology
  • Bacterial Vaccines
  • Borrelia burgdorferi Group / immunology
  • Borrelia burgdorferi Group / pathogenicity
  • Drug Resistance, Microbial
  • Genetic Variation
  • HLA-DR Antigens / immunology
  • HLA-DR4 Antigen / immunology
  • HLA-DRB1 Chains
  • Humans
  • Lipoproteins*
  • Lyme Disease / drug therapy
  • Lyme Disease / immunology*
  • Lyme Disease / microbiology
  • Lyme Disease / physiopathology
  • Lyme Disease Vaccines / genetics
  • Lyme Disease Vaccines / immunology
  • Lymphocyte Function-Associated Antigen-1 / immunology
  • United States

Substances

  • Anti-Bacterial Agents
  • Antigens, Surface
  • Autoantigens
  • Bacterial Outer Membrane Proteins
  • Bacterial Vaccines
  • HLA-DR Antigens
  • HLA-DR4 Antigen
  • HLA-DRB1 Chains
  • HLA-DRB1*04:01 antigen
  • Lipoproteins
  • Lyme Disease Vaccines
  • Lymphocyte Function-Associated Antigen-1
  • OspA protein