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A prospective study of Chlamydia pneumoniae infection and risk of MS in two US cohorts

From the Departments of Nutrition (K.L. Munger and Dr. Ascherio) and Epidemiology (Dr. Ascherio), Harvard School of Public Health, Boston, MA; Division of Research (Dr. DeLorenze), Kaiser Foundation Research Institute, Oakland, CA; Division of Preventive Medicine (L.I. Levin), Walter Reed Army Institute of Research, Washington, DC; Army Medical Surveillance Activity (Dr. Rubertone), US Army Center for Health Promotion and Preventive Medicine, Washington, DC; Orentreich Foundation for the Advancement of Science, Inc. (Drs. Vogelman and Orentreich), Cold-Spring-on-Hudson, NY; US Army Physical Disability Agency (Dr. Peck), Washington, DC; National Laboratory for Sexually Transmitted Diseases (Dr. Peeling), National Microbiology Laboratory, Winnipeg, Canada; and Channing Laboratory (Dr. Ascherio), Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA.

Address correspondence and reprint requests to Dr. Alberto Ascherio, Department of Nutrition, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115; e-mail: alberto.ascherio{at}channing.harvard.edu

Background: Chlamydia pneumoniae (Cpn) has been proposed as a possible etiologic agent in multiple sclerosis (MS). However, previous studies were cross-sectional and could not assess whether Cpn infection preceded the onset of MS.

Methods: The authors conducted a prospective nested case-control study among 3 million US Army personnel and 121,466 members of the Kaiser Permanente Medical Care Program (KPMCP) cohort. Serum samples collected prior to onset of MS symptoms were available for 83 MS cases in the Army and 46 in the KPMCP cohort. Two controls were matched to each case on age, sex, and date of blood collection. Microimmunofluorescence was used to measure serum immunoglobulin M (IgM) and immunoglobulin G (IgG) antibody titers to Cpn; IgG titers 1:16 were considered positive for past Cpn infection.

Results: Seropositivity for Cpn was not significantly associated with risk of MS in either cohort (Army: OR = 1.0; 95% CI 0.6, 1.8; KPMCP: OR = 1.5; 95% CI 0.7, 3.1) or in the pooled analysis (OR = 1.2; 95% CI 0.8, 1.9). Serum levels of anti-Cpn IgG antibody were also not associated with an increased risk of MS in the Army (OR for a fourfold difference in antibody titers = 0.9; 95% CI 0.7, 1.2) or in the pooled analysis (OR = 1.2; 95% CI 0.9, 1.4), but a significant increase in risk was seen in the KPMCP cohort (OR = 1.7; 95% CI 1.2, 2.5). The difference between these results in the Army and the KPMCP cohort was significant (p = 0.01).

Conclusions: Neither Cpn seropositivity nor serum anti-Cpn IgG antibody titers predicted risk of developing MS. However, due to the heterogeneity of results between cohorts, we cannot exclude the possibility that infection with Cpn may modify the risk of MS.

Received October 2, 2003. Accepted in final form December 30, 2003.

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