A novel human autoantigen, endothelial cell growth factor, is a target of T and B cell responses in patients with Lyme disease. Issue 1 (27th December 2012)

• Record Type: Journal Article
• Authors: Drouin, Elise E.; Seward, Robert J.; Strle, Klemen; McHugh, Gail; Katchar, Kianoosh; Londoño, Diana; Yao, Chunxiang; Costello, Catherine E.; Steere, Allen C.
• Is Part Of: Arthritis and rheumatism. Volume 65:Issue 1(2013:Jan.)
• Page Start: 186
• Page End: 196
• Publication Date: 2012-12-27
• Subjects: Arthritis -- Periodicals; Rheumatism -- Periodicals; Arthritis -- Periodicals; Rheumatic Diseases -- Periodicals; Rhumatisme -- Périodiques; Arthrite -- Périodiques; 616.72
• DOI: 10.1002/art.37732
• Languages: English
• ISSNs: 0004-3591

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <sec id="abs1-1" sec-type="section"> <title>Objective</title> <p>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.</p> </sec> <sec id="abs1-2" sec-type="section"> <title>Methods</title> <p>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.</p> </sec> <sec id="abs1-3" sec-type="section"> <title>Results</title> <p>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 (<italic>P</italic> < 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.</p> </sec> <sec id="abs1-4" sec-type="section"> <title>Conclusion</title> <p>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.</p> </sec> </abstract>