Association of a toll-like receptor 1 polymorphism with heightened Th1 inflammatory responses and antibiotic-refractory Lyme arthritis.

Authors:
Address: Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. kstrle@partners.org.
Journal:

Publication:

abstract

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.

Related Articles
Borrelia burgdorferi RST1 (OspC type A) genotype is associated with greater inflammation and more severe Lyme disease.
Am J Pathol. 2011
Borrelia burgdorferi RST1 (OspC type A) genotype is associated with greater inflammation and more severe Lyme disease.
Strle K, Jones KL, Drouin EE, Li X, Steere AC. Am J Pathol. 2011 Jun; 178(6):2726-39.
Analysis of Borrelia burgdorferi genotypes in patients with Lyme arthritis: High frequency of ribosomal RNA intergenic spacer type 1 strains in antibiotic-refractory arthritis.
Arthritis Rheum. 2009
Analysis of Borrelia burgdorferi genotypes in patients with Lyme arthritis: High frequency of ribosomal RNA intergenic spacer type 1 strains in antibiotic-refractory arthritis.
Jones KL, McHugh GA, Glickstein LJ, Steere AC. Arthritis Rheum. 2009 Jul; 60(7):2174-82.
High levels of inflammatory chemokines and cytokines in joint fluid and synovial tissue throughout the course of antibiotic-refractory lyme arthritis.
Arthritis Rheum. 2007
High levels of inflammatory chemokines and cytokines in joint fluid and synovial tissue throughout the course of antibiotic-refractory lyme arthritis.
Shin JJ, Glickstein LJ, Steere AC. Arthritis Rheum. 2007 Apr; 56(4):1325-35.
Review Relationship between immunity to Borrelia burgdorferi outer-surface protein A (OspA) and Lyme arthritis.
Clin Infect Dis. 2011
Review Relationship between immunity to Borrelia burgdorferi outer-surface protein A (OspA) and Lyme arthritis.
Steere AC, Drouin EE, Glickstein LJ. Clin Infect Dis. 2011 Feb; 52 Suppl 3:s259-65.
Review Infectious arthritis and immune dysregulation: lessons from Lyme disease.
Curr Opin Rheumatol. 2010
Review Infectious arthritis and immune dysregulation: lessons from Lyme disease.
Iliopoulou BP, Huber BT. Curr Opin Rheumatol. 2010 Jul; 22(4):451-5.

To top • Home

TraveldoctorOnline 2001 • Disclaimer • webmaster

The contents within traveldoctoronline are presented only for informational purposes and cannot substitute for professional health care or any other medical treatment.All users of this website with health problems should be oblige always to consult their medical doctor before starting any treatment.