Association of a Toll‐like receptor 1 polymorphism with heightened Th1 inflammatory responses and antibiotic‐refractory Lyme arthritis
Abstract
ARTHRITIS & RHEUMATISM Vol. 64, No. 5, May 2012, pp 1497–1507 DOI 10.1002/art.34383 © 2012, American College of Rheumatology Association of a Toll-like Receptor 1 Polymorphism With Heightened Th1 Inflammatory Responses and Antibiotic-Refractory Lyme Arthritis Klemen Strle, Junghee J. Shin, Lisa J. Glickstein, and Allen C. Steere 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 out- comes 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 arthri- tis, and supernatants of Borrelia burgdorferi–stimulated peripheral blood mononuclear cells (PBMCs) from pa- tients with Lyme arthritis. Results. The frequency of the TLR1-1805GG poly- morphism 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- (IFN), CXCL9, and CXCL10 and had more severe infection than EM pa- tients 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 stimu- lated with a B burgd
Key Biomarkers
Symptom Clusters
Cited By (2)
References (9)
- Chemokine Signatures in the Skin Disorders of Lyme Borreliosis in Europe: Predominance of CXCL9 and CXCL10 in Erythema Migrans and Acrodermatitis and CXCL13 in LymphocytomaInfection and Immunity · 2007
- High levels of inflammatory chemokines and cytokines in joint fluid and synovial tissue throughout the course of antibiotic‐refractory lyme arthritisArthritis & Rheumatism · 2007
- Borrelia burgdorferi Genetic Markers and Disseminated Disease in Patients with Early Lyme DiseaseJournal of Clinical Microbiology · 2006
- Treg cell numbers and function in patients with antibiotic‐refractory or antibiotic‐responsive lyme arthritisArthritis & Rheumatism · 2010
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