Need for an external proficiency testing program for cytokines, chemokines, and plasma markers of immune activation

An external evaluation program for measuring the performance of laboratorie s testing for cytokines and immune activation markers in biological fluids was developed, Cytokines, chemokines, soluble cytokine receptors, and other soluble markers of immune activation (CSM) were measured in plasma from a healthy human immunodeficiency virus (HIV)-seronegative reference populatio n and from HIV-seropositive individuals as well as in supernatant fluids fr om in vitro-stimulated human immune cells. The 14 components measured were tumor necrosis factor (TNF) alpha, gamma interferon, interleukin-1 (IL-1), IL-2, n-4, IL-6, IL-10, Rantes, MIP-Ia, MIP-I beta, soluble TNF receptor II , soluble IL-2 receptor alpha, beta(2)-microglobulin, and neopterin. Twelve laboratories associated with the Adult and Pediatric AIDS Clinical Trial G roups participated in the study. The performance features that were evaluat ed included intralaboratory variability, interlaboratory variability, compa rison of reagent sources, and ability to detect CSM in the plasma of normal subjects as well as the changes occurring in disease. The principal findin gs were as follows: (i) on initial testing, i.e., before participating in t he program, laboratories frequently differed markedly in their analytic res ults; (ii) the quality of testing of a CSM in individual participating labo ratories could be assessed; (iii) most commercial kits allowed distinction between normal and abnormal plasma CSM levels and between supernatants of s timulated and unstimulated cells; (iv) different sources of reagents and re ference standards frequently provided different absolute values; (v) inexpe rienced laboratories can benefit from participating in the program; (vi) la boratory performance improved during active participation in the program; a nd (vii) comparability between analyses conducted at different sites can be ensured by an external proficiency testing program.