Document Detail


A novel human autoantigen, endothelial cell growth factor, is a target of T and B cell responses in patients with Lyme disease.
MedLine Citation:
PMID:  23044924     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Elise E Drouin; Robert J Seward; Klemen Strle; Gail McHugh; Kianoosh Katchar; Diana Londoño; Chunxiang Yao; Catherine E Costello; Allen C Steere
Related Documents :
14871274 - Human embryonic stem cells: a potential source for cellular therapy.
24759184 - Increased activated natural killer t cells in the liver of patients with advancedstage ...
23596304 - Potential of herpesvirus saimiri-based vectors to reprogram a somatic ewing's sarcoma f...
24704664 - Limited efficacy of immunosuppressive drugs on cd8+ t cell-mediated and natural killer ...
12499424 - Diagnostic role of tests for t cell receptor (tcr) genes.
16618774 - Characterization of the mouse ifn-lambda ligand-receptor system: ifn-lambdas exhibit an...
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Arthritis and rheumatism     Volume:  65     ISSN:  1529-0131     ISO Abbreviation:  Arthritis Rheum.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-01-02     Completed Date:  2013-03-17     Revised Date:  2014-01-09    
Medline Journal Info:
Nlm Unique ID:  0370605     Medline TA:  Arthritis Rheum     Country:  United States    
Other Details:
Languages:  eng     Pagination:  186-96     Citation Subset:  AIM; IM    
Copyright Information:
Copyright © 2013 by the American College of Rheumatology.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Autoantigens / immunology*
B-Lymphocytes / immunology*,  metabolism
Drug Resistance, Bacterial
Endothelial Growth Factors / immunology*
Enzyme-Linked Immunosorbent Assay
Enzyme-Linked Immunospot Assay
HLA-DR Antigens / immunology*,  metabolism
Humans
Immunoblotting
Immunohistochemistry
Lyme Disease / drug therapy,  immunology*,  metabolism
Proteomics
T-Lymphocytes
Tandem Mass Spectrometry
Grant Support
ID/Acronym/Agency:
AR-20358/AR/NIAMS NIH HHS; HHSN268201000031C/HL/NHLBI NIH HHS; N01-HV-00239/HV/NHLBI NIH HHS; N01-HV-28178/HV/NHLBI NIH HHS; N01HV28178/HL/NHLBI NIH HHS; P41 GM104603/GM/NIGMS NIH HHS; P41 RR010888/RR/NCRR NIH HHS; P41-GM-104603/RR-10888/GM/NIGMS NIH HHS; R01 AR020358/AR/NIAMS NIH HHS; S10 RR015942/RR/NCRR NIH HHS; S10 RR020946/RR/NCRR NIH HHS; S10-RR-15942/RR/NCRR NIH HHS; S10-RR-20946/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Autoantigens; 0/Endothelial Growth Factors; 0/HLA-DR Antigens
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Lack of MMP10 exacerbates experimental colitis and promotes development of inflammation-associated c...
Next Document:  Highly Diastereo- and Enantioselective Organocatalytic One-Pot Sequential 1,4-Addition/Dearomative-F...