When is enough measurement, enough? Generalizability of primate immunity over time

A statistical generalizability analysis gauges the degree to which a single assessment of a parameter successfully estimates that measure over repeated assessments for that individual. The generalizability of enumerative and functional immune parameters was estimated for two species of macaque monkeys assessed every 3 months between 18 and 42 months of age. Subjects were cross-balanced by species (bonnet, Macaca radiata, n = 22; pigtail, Macaca nemestrina, n = 21), sex (male, n = 21; female, n = 22), and brief early maternal separation with reunion (control, n = 21; separated, n = 22). Cell subset analysis showed the best generalizability (35-69%). Natural cytotoxicity also performed well (44-70%), but when computed on a lysis per cell basis, removing the effect of cell phenotype, it was less stable (15-48%). For most immune parameters, at least 5 assessments would be necessary to establish conventionally reliable (0.80) characterizations of long-term, stable individual differences in immunity, and three for minimally reliable (0.60) characterizations. More reactive parameters, as well as more behaviorally reactive species, yielded more generalizable results. Cell subsets that are typically most sensitive to acute stress (CD8, CD16) were more stable than other subsets (CD4, CD20). Behaviorally reactive species (pigtail) yielded more stable natural cytotoxicity results than the less reactive species (bonnet). Sex and rearing condition (early, brief maternal separation) did not substantially affect generalizability, although females tended to generate more stable results than did males.