| Association of a Toll-like receptor 1 polymorphism with heightened Th1 inflammatory responses and antibiotic-refractory Lyme arthritis. | |
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MedLine Citation:
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PMID: 22246581 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVE: Single-nucleotide polymorphisms (SNPs) that alter immune function, inflammatory responses, and disease susceptibility have been identified in several genes encoding Toll-like receptors (TLRs). The TLR SNPs with the best evidence of an effect on immune function are those in TLR1 (1805GG), TLR2 (2258GA), and TLR5 (1174CT). This study was undertaken to assess the frequency and functional outcomes of these polymorphisms in patients with Lyme disease. METHODS: SNP frequencies and functional outcomes were assessed in 248 patients with Lyme disease. Cytokine and chemokine levels were determined using multiplex assays in the serum of patients with erythema migrans (EM), joint fluid of patients with Lyme arthritis, and supernatants of Borrelia burgdorferi-stimulated peripheral blood mononuclear cells (PBMCs) from patients with Lyme arthritis. RESULTS: The frequency of the TLR1-1805GG polymorphism was greater in patients with antibiotic-refractory arthritis compared with patients with EM or those with antibiotic-responsive arthritis. Early in the illness, patients with EM carrying 1805GG, primarily those infected with B burgdorferi 16S-23S ribosomal spacer RNA intergenic type 1 (RST1) strains, had higher serum levels of interferon-γ (IFNγ), CXCL9, and CXCL10 and had more severe infection than EM patients carrying the 1805TG/TT polymorphism. These inflammatory responses were amplified in patients with Lyme arthritis, and the highest responses were observed in patients with 1805GG in the antibiotic-refractory group who had been infected with RST1 strains. When PBMCs from patients with Lyme arthritis were stimulated with a B burgdorferi RST1 strain, the 1805GG group had a significantly larger fold increase in the levels of IFNγ, CCL2, CXCL9, and CXCL10 compared to the 1805TG/TT group. In contrast, the TLR2 and TLR5 polymorphisms did not vary in frequency or function among the groups. CONCLUSION: The TLR1-1805GG polymorphism in B burgdorferi RST1-infected patients was associated with stronger Th1-like inflammatory responses, an environment that 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; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Arthritis and rheumatism Volume: 64 ISSN: 1529-0131 ISO Abbreviation: Arthritis Rheum. Publication Date: 2012 May |
Date Detail:
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Created Date: 2012-04-27 Completed Date: 2012-07-13 Revised Date: 2013-05-03 |
Medline Journal Info:
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Nlm Unique ID: 0370605 Medline TA: Arthritis Rheum Country: United States |
Other Details:
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Languages: eng Pagination: 1497-507 Citation Subset: AIM; IM |
Copyright Information:
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Copyright © 2012 by the American College of Rheumatology. |
Affiliation:
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Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA. kstrle@partners.org |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adolescent Adult Aged Anti-Bacterial Agents / therapeutic use* Biological Markers / blood Borrelia burgdorferi / classification, drug effects, genetics Cells, Cultured Chemokine CXCL10 / blood Chemokine CXCL9 / blood Child Drug Resistance, Bacterial / genetics* Humans Interferon-gamma / blood Joints / microbiology, pathology Leukocytes, Mononuclear Lyme Disease* / drug therapy, genetics, immunology Middle Aged Polymorphism, Single Nucleotide* Synovial Fluid / metabolism, microbiology Synovitis* / genetics, immunology, pathology Th1 Cells / immunology*, pathology Toll-Like Receptor 1 / genetics*, metabolism Young Adult |
| Grant Support | |
ID/Acronym/Agency:
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AR-007258/AR/NIAMS NIH HHS; AR-020358/AR/NIAMS NIH HHS; R01 AR020358-36/AR/NIAMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Anti-Bacterial Agents; 0/Biological Markers; 0/CXCL10 protein, human; 0/CXCL9 protein, human; 0/Chemokine CXCL10; 0/Chemokine CXCL9; 0/Toll-Like Receptor 1; 82115-62-6/Interferon-gamma |
| Comments/Corrections | |
Comment In:
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Arthritis Rheum. 2012 May;64(5):1311-5
[PMID:
22246662
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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