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Serologic Assessment of Type 1 and Type 2 Immunity in Healthy Japanese Adults

Departments of ¹ Epidemiology and ² Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts; Departments of ³ Laboratory Medicine and ⁴ Internal Medicine II, Miyazaki Medical College, Miyazaki, Japan; ⁵ Division of Biostatistics and Epidemiology, University of Massachusetts Medical School Cancer Center, Worcester, Massachusetts; ⁶ Miyazaki Prefectural Nursing University, Miyazaki, Japan; ⁷ Nectandra Institute, San Ramon, Costa Rica; and ⁸ Department of Epidemiology, Boston University School of Public Health, Boston, Massachusetts

Requests for reprints: Brenda M. Birmann, Department of Epidemiology, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA 02115. Phone: 617-432-1221; Fax: 617-432-4626. E-mail: bbirmann{at}hsph.harvard.edu

We assessed the informativeness of several serologic biomarkers of immune function using serum specimens collected in the Miyazaki Cohort Study from subjects who were seronegative for anti–human T-cell lymphotrophic virus I and anti–hepatitis C virus. To broadly characterize type 1 immune status, we measured EBV antibody titers, because titer profiles associated with cellular immune suppression are well described. We also tested for three type 2 biomarkers: total serum IgE, soluble CD23, and soluble CD30. Nonreactivity to a tuberculin purified protein derivative (PPD) skin test is indicative of diminished delayed-type hypersensitivity (type 1) responsiveness in the study population due to a history of tuberculosis exposure or Bacillus Calmette-Guérin vaccination. We therefore evaluated the serologic markers as predictors of PPD nonreactivity using logistic regression. Subjects whose EBV antibody profiles were consistent with deficient type 1 immunity were more than thrice as likely to be PPD nonreactive as persons with "normal" antibody titers. Elevated total IgE was also strongly associated with PPD nonreactivity (odds ratio 3.4, 95% confidence interval 1.2-9.9); elevated soluble CD23 had a weaker, but positive, odds ratio, whereas soluble CD30 levels were not predictive of PPD status. Therefore, PPD nonreactivity is associated, in this population, with a pattern of serum biomarkers that is indicative of diminished type 1 and elevated type 2 immunity. We conclude that, with the exception of soluble CD30, the serologic markers are informative for the characterization of type 1/type 2 immune status using archived sera from study populations of healthy adults.