Association of antibiotic treatment-resistant Lyme arthritis with T cell responses to dominant epitopes of outer surface protein A of Borrelia burgdorferi

Arthritis Rheum. 1999 Sep;42(9):1813-22. doi: 10.1002/1529-0131(199909)42:9<1813::AID-ANR4>3.0.CO;2-0.


Objective: To explore further the association of antibiotic treatment-resistant Lyme arthritis and T cell reactivity with outer surface protein A (OspA) of Borrelia burgdorferi, including the identification of T cell epitopes associated with this treatment-resistant course.

Methods: The responses of peripheral blood and, if available, synovial fluid lymphocytes to B burgdorferi proteins, fragments, and synthetic peptides, as determined by proliferation assay and interferon-gamma production, were compared in 16 patients with treatment-responsive and 16 with treatment-resistant Lyme arthritis.

Results: The maximum severity of joint swelling correlated directly with the response to OspA. Moreover, the only significant difference between patients with treatment-resistant and treatment-responsive arthritis was in reactivity with N-terminal and C-terminal fragments of OspA, OspA1 (amino acids [aa] 16-106), and OspA3 (aa 168-273). Epitope mapping showed that 14 of the 16 patients with treatment-resistant arthritis had responses to OspA peptides (usually 4 or 5 epitopes), whereas only 5 of the 16 patients with treatment-responsive arthritis had reactivity with these peptides (usually 1 or 2 epitopes) (P = 0.003). Patients with HLA-DRB1 alleles associated with treatment-resistant arthritis were more likely to react with peptide 15 (aa 154-173) and, to a lesser degree, with peptide 21 (aa 214-233) than patients with other alleles, whereas the responses to other epitopes were similar in both groups.

Conclusion: The maximum severity of joint swelling and the duration of Lyme arthritis after antibiotic treatment are associated with T cell responses to specific epitopes of OspA.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Alleles
  • Anti-Bacterial Agents / therapeutic use
  • Antibody Formation
  • Antigens, Surface / immunology*
  • Bacterial Outer Membrane Proteins / immunology*
  • Bacterial Vaccines / immunology
  • Borrelia burgdorferi Group
  • Child
  • Doxycycline / therapeutic use
  • Drug Resistance, Microbial / immunology*
  • Epitope Mapping
  • Epitopes, T-Lymphocyte / drug effects
  • Female
  • HLA Antigens / genetics
  • Humans
  • Immunodominant Epitopes / immunology
  • Lipoproteins*
  • Lyme Disease / drug therapy*
  • Lyme Disease / immunology*
  • Male
  • Middle Aged
  • Severity of Illness Index
  • T-Lymphocytes / immunology
  • Tetracycline Resistance / immunology
  • Time Factors


  • Anti-Bacterial Agents
  • Antigens, Surface
  • Bacterial Outer Membrane Proteins
  • Bacterial Vaccines
  • Epitopes, T-Lymphocyte
  • HLA Antigens
  • Immunodominant Epitopes
  • Lipoproteins
  • OspA protein
  • Doxycycline