- Lyme disease, which is caused by the tick-borne spirochete, Borrelia burgdorferi, is now the most common vector-borne infection in the United States. The broad range goal of this grant proposal is to understand the pathogenesis of chronic Lyme arthritis, a severe manifestation of the illness that may not respond to antibiotic therapy. In an effort to achieve this goal, the Lyme disease spirochete or its DNA or antigens will be sought in the joint fluid or synovium of patients with treatment-responsive or treatment-resistant Lyme arthritis. Since particular immune responses early in the infection correlate with the subsequent severity and duration of arthritis, specific immune factors will be determined both in patients with erythema migrans, the first sign of the infection, and in those with treatment-responsive or treatment-resistant arthritis, which occurs months to years after disease onset. These factors include 1) T and B cell reactivity with B. burgdorferi antigens, particularly to epitopes of outer-surface protein A (OspA), 2) the phenotype of T helper cells (Th1 or Th2) induced by spirochetal antigens, especially by OspA, and 3) the lymphokines and monokines present in erythema migrans or synovial lesions. The epitopes of OspA recognized, the cytokines produced, and the HLA-DR alleles of patients will be correlated with clinical findings in an effort to implicate particular immune responses in the pathogenesis of treatment-resistant arthritis. In addition to providing information about the pathogenesis and appropriate treatment of Lyme arthritis, these studies may give clues regarding the pathogenesis of other forms of chronic inflammatory arthritis in which the cause is not yet known, including rheumatoid arthritis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR020358-25
Application #
6171416
Study Section
General Medicine A Subcommittee 2 (GMA)
Program Officer
Serrate-Sztein, Susana
Project Start
1987-07-01
Project End
2001-03-31
Budget Start
2000-04-01
Budget End
2001-03-31
Support Year
25
Fiscal Year
2000
Total Cost
$378,157
Indirect Cost
Name
Tufts University
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02111
Vudattu, Nalini K; Strle, Klemen; Steere, Allen C et al. (2013) Dysregulation of CD4+CD25(high) T cells in the synovial fluid of patients with antibiotic-refractory Lyme arthritis. Arthritis Rheum 65:1643-53
Drouin, Elise E; Seward, Robert J; Strle, Klemen et al. (2013) A novel human autoantigen, endothelial cell growth factor, is a target of T and B cell responses in patients with Lyme disease. Arthritis Rheum 65:186-96
Katchar, Kia; Drouin, Elise E; Steere, Allen C (2013) Natural killer cells and natural killer T cells in Lyme arthritis. Arthritis Res Ther 15:R183
Li, Xin; Strle, Klemen; Wang, Peng et al. (2013) Tick-specific borrelial antigens appear to be upregulated in American but not European patients with Lyme arthritis, a late manifestation of Lyme borreliosis. J Infect Dis 208:934-41
Strle, Klemen; Shin, Junghee J; Glickstein, Lisa J et al. (2012) Association of a Toll-like receptor 1 polymorphism with heightened Th1 inflammatory responses and antibiotic-refractory Lyme arthritis. Arthritis Rheum 64:1497-507
Seward, Robert J; Drouin, Elise E; Steere, Allen C et al. (2011) Peptides presented by HLA-DR molecules in synovia of patients with rheumatoid arthritis or antibiotic-refractory Lyme arthritis. Mol Cell Proteomics 10:M110.002477
Li, Xin; McHugh, Gail A; Damle, Nitin et al. (2011) Burden and viability of Borrelia burgdorferi in skin and joints of patients with erythema migrans or lyme arthritis. Arthritis Rheum 63:2238-47
Steere, Allen C; Drouin, Elise E; Glickstein, Lisa J (2011) Relationship between immunity to Borrelia burgdorferi outer-surface protein A (OspA) and Lyme arthritis. Clin Infect Dis 52 Suppl 3:s259-65
Strle, Klemen; Jones, Kathryn L; Drouin, Elise E et al. (2011) Borrelia burgdorferi RST1 (OspC type A) genotype is associated with greater inflammation and more severe Lyme disease. Am J Pathol 178:2726-39
Yakimchuk, Konstantin; Roura-Mir, Carme; Magalhaes, Kelly G et al. (2011) Borrelia burgdorferi infection regulates CD1 expression in human cells and tissues via IL1-?. Eur J Immunol 41:694-705

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