A novel human autoantigen, endothelial cell growth factor, is a target of T and B cell responses in patients with Lyme disease

Arthritis Rheum. 2013 Jan;65(1):186-96. doi: 10.1002/art.37732.


Objective: Autoantigen presentation by HLA-DR molecules is thought to be a central component of many autoimmune diseases, but identifying disease-relevant autoantigens has been a difficult challenge. In this study we aimed to identify autoantigens in patients with antibiotic-refractory Lyme arthritis, in which infection-induced autoimmunity is thought to play an important role.

Methods: Using tandem mass spectrometry, naturally presented HLA-DR self peptides from a patient's synovium were identified, synthesized, and reacted with his peripheral blood mononuclear cells (PBMCs). Immunoreactive peptides and their source proteins were then tested for T and B cell responses using large numbers of patient cells or sera.

Results: Of 120 HLA-DR-presented self peptides identified from one patient, one peptide derived from endothelial cell growth factor (ECGF) caused his PBMCs to proliferate. T and B cell responses to ECGF occurred systemically in ∼10-30% of patients with early or late manifestations of Lyme disease, primarily in those with refractory arthritis-associated HLA-DR alleles, such as DRB1*0101 and 0401. Compared with patients with antibiotic-responsive arthritis, those with antibiotic-refractory arthritis had significantly higher concentrations of ECGF in synovial fluid (P<0.0001) and more often had ECGF antibody reactivity. Among non-antibiotic-treated historical patients who developed arthritis, 26% had ECGF reactivity, which often developed before the onset of arthritis and was associated with significantly longer courses of arthritis.

Conclusion: T and B cell responses to ECGF occur in a subset of patients with Lyme disease, particularly in those with antibiotic-refractory arthritis, providing the first direct evidence of autoimmune T and B cell responses in this illness.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autoantigens / immunology*
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • Drug Resistance, Bacterial
  • Endothelial Growth Factors / immunology*
  • Enzyme-Linked Immunosorbent Assay
  • Enzyme-Linked Immunospot Assay
  • HLA-DR Antigens / immunology*
  • HLA-DR Antigens / metabolism
  • Humans
  • Immunoblotting
  • Immunohistochemistry
  • Lyme Disease / drug therapy
  • Lyme Disease / immunology*
  • Lyme Disease / metabolism
  • Proteomics
  • T-Lymphocytes
  • Tandem Mass Spectrometry


  • Autoantigens
  • Endothelial Growth Factors
  • HLA-DR Antigens