The objective is to define pathogenic mechanisms involved in chronic fatigue syndrome. Studies will concentrate on patients with chronic fatigue + cognitive impairment following infection by the spirochete B.burgdorferi (Bb) (the cause of Lyme disease). Controls will be matched Bb-infected subjects without such problems. Subjects will be evaluated at single time points and serially for clinical parameters (using fatigue and cognition rating scales) and immune parameters. The following specific points will be addressed: 1. Are predisposing factors involved? Document HLA-DR type, allergy history, depression/psychologic profile, and skin test response of patients vs. controls. 2. Is immune activation involved? Examine blood and cerebrospinal fluid for immune complexes (IC) using polyethylene glycol, chromatography, and Raji cell assay; spontaneous, mitogen, and antigen-induced lymphocyte proliferation; and cytokines/soluble markers using ELISA in patients vs. controls. 3. Is immune activation directed against Bb? Isolate IC to probe for anti-Bb antibodies. Compare in vitro lymphocyte reactivity and cytokine production to Bb in patients vs. controls. 4. Compare the immune profile of patient with fatigue alone vs cognitive impairment. Correlate humoral, cellular, and soluble immune parameters with measured clinical parameters of fatigue and cognition. 5. Do fatigue or cognitively impaired patients have persistent Bb infection? Probe isolated IC for Bb antigens using monoclonal/polyclonal antibodies, ELISA, and immunoblot. This study targets a specific subgroup of postinfectious fatigue patients to examine the role of immune activation and persistent infection in their fatigue, and the relationship of cognitive impairment to fatigue. This work should provide insights for the heterogeneous group of patients with chronic fatigue syndromes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI031561-03
Application #
2066541
Study Section
Epidemiology and Disease Control Subcommittee 2 (EDC)
Project Start
1992-04-01
Project End
1996-03-31
Budget Start
1994-04-01
Budget End
1996-03-31
Support Year
3
Fiscal Year
1994
Total Cost
Indirect Cost
Name
State University New York Stony Brook
Department
Neurology
Type
Schools of Medicine
DUNS #
804878247
City
Stony Brook
State
NY
Country
United States
Zip Code
11794
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Schutzer, S E; Coyle, P K; Reid, P et al. (1999) Borrelia burgdorferi-specific immune complexes in acute Lyme disease. JAMA 282:1942-6
Gaudino, E A; Coyle, P K; Krupp, L B (1997) Post-Lyme syndrome and chronic fatigue syndrome. Neuropsychiatric similarities and differences. Arch Neurol 54:1372-6
Krupp, L B; Sliwinski, M; Masur, D M et al. (1994) Cognitive functioning and depression in patients with chronic fatigue syndrome and multiple sclerosis. Arch Neurol 51:705-10
Coyle, P K; Krupp, L B; Doscher, C et al. (1994) Borrelia burgdorferi reactivity in patients with severe persistent fatigue who are from a region in which Lyme disease is endemic. Clin Infect Dis 18 Suppl 1:S24-7
Krupp, L B; Masur, D M; Kaufman, L D (1993) Neurocognitive dysfunction in the eosinophilia-myalgia syndrome. Neurology 43:931-6
Coyle, P K (1993) Neurologic complications of Lyme disease. Rheum Dis Clin North Am 19:993-1009
Coyle, P K; Krupp, L B; Doscher, C (1993) Significance of reactive Lyme serology in multiple sclerosis. Ann Neurol 34:745-7
Coyle, P K; Deng, Z; Schutzer, S E et al. (1993) Detection of Borrelia burgdorferi antigens in cerebrospinal fluid. Neurology 43:1093-8