| A Toll-like receptor 1 polymorphism is associated with heightened T-helper 1 inflammatory responses and antibiotic-refractory lyme arthritis. | |
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MedLine Citation:
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PMID: 22246581 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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OBJECTIVE.: Single-nucleotide polymorphisms (SNPs) have been identified in several genes encoding Toll-like receptors (TLRs) that alter immune function, inflammatory responses and disease susceptibility. The SNPs with best evidence for affecting immune function are TLR1 (1805GG), TLR2 (2258GA) and TLR5 (1174CT). METHODS.: We studied the frequency and functional outcome of these polymorphisms in 248 patients with Lyme disease. Cytokine and chemokine levels were determined in serum of patients with erythema migrans (EM), joint fluid of patients with Lyme arthritis, and supernatants of B. burgdorferi-stimulated PBMC from Lyme arthritis patients, using multiplex assays. RESULTS.: The frequency of TLR1-1805GG polymorphism was greater in patients with antibiotic-refractory arthritis compared with patients with EM or antibiotic-responsive arthritis. Early in the illness, EM patients with 1805GG, primarily those infected with B. burgdorferi RST1 strains, had higher serum levels of IFNγ, CXCL9 and CXCL10, and more severe infection than patients with 1805TG/TT. These inflammatory responses were amplified in patients with Lyme arthritis, and the highest responses were observed in antibiotic-refractory arthritis patients with 1805GG who had been infected with RST1 strains. When PBMC from Lyme arthritis patients were stimulated with a B. burgdorferi RST1 strain, the 1805GG group had significantly larger fold-increase in the levels of IFNγ, CCL2, CXCL9 and CXCL10, than the 1805TG/TT group. In contrast, the TLR2 and TLR5 polymorphisms did not vary among groups in frequency or function. CONCLUSION.: The TLR1-1805GG polymorphism in B. burgdorferi RST1-infected patients was associated with stronger T(H) 1-like inflammatory responses, which may set the stage for antibiotic-refractory arthritis. |
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Authors:
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Klemen Strle; Junghee J Shin; Lisa J Glickstein; Allen C Steere |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-1-13 |
Journal Detail:
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Title: Arthritis and rheumatism Volume: - ISSN: 1529-0131 ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2012-1-16 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0370605 Medline TA: Arthritis Rheum Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2012 by the American College of Rheumatology. |
Affiliation:
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Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA. kstrle@partners.org. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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