{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T06:09:39Z","timestamp":1791266979480,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2012,4,26]],"date-time":"2012-04-26T00:00:00Z","timestamp":1335398400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2012,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Single\u2010nucleotide polymorphisms (SNPs) that alter immune function, inflammatory responses, and disease susceptibility have been identified in several genes encoding Toll\u2010like receptors (TLRs). The <jats:italic>TLR<\/jats:italic> SNPs with the best evidence of an effect on immune function are those in <jats:italic>TLR1<\/jats:italic> (1805GG), <jats:italic>TLR2<\/jats:italic> (2258GA), and <jats:italic>TLR5<\/jats:italic> (1174CT). This study was undertaken to assess the frequency and functional outcomes of these polymorphisms in patients with Lyme disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>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 <jats:italic>Borrelia burgdorferi<\/jats:italic>\u2013stimulated peripheral blood mononuclear cells (PBMCs) from patients with Lyme arthritis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The frequency of the <jats:italic>TLR1<\/jats:italic>\u20101805GG polymorphism was greater in patients with antibiotic\u2010refractory arthritis compared with patients with EM or those with antibiotic\u2010responsive arthritis. Early in the illness, patients with EM carrying 1805GG, primarily those infected with <jats:italic>B burgdorferi<\/jats:italic> 16S\u201323S ribosomal spacer RNA intergenic type 1 (RST1) strains, had higher serum levels of interferon\u2010\u03b3 (IFN\u03b3), 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\u2010refractory group who had been infected with RST1 strains. When PBMCs from patients with Lyme arthritis were stimulated with a <jats:italic>B burgdorferi<\/jats:italic> RST1 strain, the 1805GG group had a significantly larger fold increase in the levels of IFN\u03b3, CCL2, CXCL9, and CXCL10 compared to the 1805TG\/TT group. In contrast, the <jats:italic>TLR2<\/jats:italic> and <jats:italic>TLR5<\/jats:italic> polymorphisms did not vary in frequency or function among the groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The <jats:italic>TLR1<\/jats:italic>\u20101805GG polymorphism in <jats:italic>B burgdorferi<\/jats:italic> RST1\u2013infected patients was associated with stronger Th1\u2010like inflammatory responses, an environment that may set the stage for antibiotic\u2010refractory arthritis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.34383","type":"journal-article","created":{"date-parts":[[2012,1,13]],"date-time":"2012-01-13T19:12:30Z","timestamp":1326481950000},"page":"1497-1507","source":"Crossref","is-referenced-by-count":145,"title":["Association of a Toll\u2010like receptor 1 polymorphism with heightened Th1 inflammatory responses and antibiotic\u2010refractory Lyme 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