title: A novel human autoantigen, endothelial cell growth factor, is a target of T and B cell responses in patients with Lyme disease.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA. edrouin@partners.org
authors.forename: Elise E
authors.initials: EE
authors.lastname: Drouin
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Seward
authors.forename: Klemen
authors.initials: K
authors.lastname: Strle
authors.forename: Gail
authors.initials: G
authors.lastname: McHugh
authors.forename: Kianoosh
authors.initials: K
authors.lastname: Katchar
authors.forename: Diana
authors.initials: D
authors.lastname: Londoño
authors.forename: Chunxiang
authors.initials: C
authors.lastname: Yao
authors.forename: Catherine E
authors.initials: CE
authors.lastname: Costello
authors.forename: Allen C
authors.initials: AC
authors.lastname: Steere
mesh_terms: D001324:Autoantigens / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D024881:Drug Resistance, Bacterial; D016228:Endothelial Growth Factors / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D058501:Enzyme-Linked Immunospot Assay; D006684:HLA-DR Antigens / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D008193:Lyme Disease / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D040901:Proteomics; D013601:T-Lymphocytes; D053719:Tandem Mass Spectrometry
chemical_list: D001324:Autoantigens; D016228:Endothelial Growth Factors; D006684:HLA-DR Antigens