Article

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

Hospital and Harvard Medical School, Boston, Massachusetts
Arthritis & Rheumatology (Impact Factor: 7.87). 01/2013; 65(1). DOI: 10.1002/art.37732
Source: PubMed

ABSTRACT OBJECTIVE.: Autoantigen presentation by HLA-DR molecules is thought to be a central component of many autoimmune diseases, but uncovering disease-relevant autoantigens has been a difficult challenge. Our goal was to identify autoantigens in patients with antibiotic-refractory Lyme arthritis, which is thought to result from infection-induced autoimmunity. 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 (PBMC). Immunoreactive peptides and their source proteins were then tested for T and B cell responses using large numbers of patients' 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 PBMC to proliferate. We then found that T and B cell responses to ECGF occurred systemically in about 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. In non-antibiotic-treated historic 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 for autoimmune T and B cell responses in this illness. © 2012 American College of Rheumatology.

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Available from: Elise E Drouin, Oct 06, 2014
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