title: Levels of cytokines and immune activation markers in plasma in human immunodeficiency virus infection: quality control procedures.
abstract: Procedures for quality control (QC) in a laboratory that concentrates on cytokine and soluble marker measurements in biological fluids are outlined. Intra-assay, interassay, and interlaboratory experiences are presented. Plasma and serum beta2-microglobulin (beta2M) and neopterin test data are presented in greatest detail, along with substantial tumor necrosis factor alpha (TNF-alpha), gamma interferon, soluble interleukin-2 receptor-alpha (sIL-2Ralpha), sTNF-RII, IL-4, and IL-6 data. Recommended QC procedures for cytokine and soluble-marker testing include replicate testing of two or more reference samples provided by the kit manufacturer, replicate testing of in-house frozen reference QC samples that represent normal and abnormal analyte contents, retesting 15 to 20% of randomly selected samples, and comparing normal reference ranges each year. Also, eight cytokines and soluble markers were evaluated in human immunodeficiency virus (HIV)-seronegative and HIV-seropositive individuals stratified on the basis of CD4 T-cell numbers. Levels of some but not all cytokines in serum increased in HIV infection. There was a tendency for cytokines to increase with more advanced disease, defined by reduced CD4 T-cell numbers. Cytokine changes did not relate closely to CD4 level, indicating that separate information was provided by the measurements of TNF-alpha, sTNF-RII, sIL-2Ralpha, beta2M, and neopterin. Serum IL-4 and TNF-alpha levels were not increased. The quality of laboratory data can impact on clinical relevance. Interlaboratory comparisons revealed substantial differences at some sites and documented the need for external proficiency-testing quality assurance programs.
authors.affiliation: Department of Microbiology and Immunology, Center for Interdisciplinary Research in Immunology and Disease, Jonsson Comprehensive Cancer Center and UCLA AIDS Institute, UCLA School of Medicine, Los Angeles, California 90095-1747, naziz@ucla.edu
authors.forename: N
authors.initials: N
authors.lastname: Aziz
authors.forename: P
authors.initials: P
authors.lastname: Nishanian
authors.forename: J L
authors.initials: JL
authors.lastname: Fahey
mesh_terms: D015415:Biomarkers / Q000097:blood; D001774:Blood Chemical Analysis / Q000592:standards*; D018791:CD4 Lymphocyte Count; D016207:Cytokines / Q000097:blood*; D015658:HIV Infections / Q000175:diagnosis* / Q000276:immunology*; D006801:Humans; D007124:Immunoenzyme Techniques; D007753:Laboratories / Q000592:standards; D019798:Neopterin / Q000097:blood*; D011786:Quality Control; D011863:Radioimmunoassay; D011933:Reagent Kits, Diagnostic; D012016:Reference Values; D015203:Reproducibility of Results; D001613:beta 2-Microglobulin / Q000032:analysis*
chemical_list: D015415:Biomarkers; D016207:Cytokines; D011933:Reagent Kits, Diagnostic; D001613:beta 2-Microglobulin; D019798:Neopterin