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Clinical and Diagnostic Laboratory Immunology, November 1998, p. 755-761, Vol. 5, No. 6
1071-412X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Levels of Cytokines and Immune Activation Markers in Plasma in Human Immunodeficiency Virus Infection: Quality Control Procedures

Najib Aziz,1,* Parunag Nishanian,1 and John L. Fahey1,2

Departments of Medicine2 and Microbiology and Immunology,1 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

Received 15 May 1998/Returned for modification 8 July 1998/Accepted 28 July 1998

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 beta 2-microglobulin (beta 2M) 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 , beta 2M, 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.


* Corresponding author. Mailing address: Department of Microbiology and Immunology, UCLA School of Medicine, Los Angeles, CA 90095-1747. Phone: (310) 825-0825. Fax: (310) 825-0595. E-mail: naziz{at}ucla.edu.


Clinical and Diagnostic Laboratory Immunology, November 1998, p. 755-761, Vol. 5, No. 6
1071-412X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.



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