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Amino acid residue at position 13 in HLA-DR beta chain plays a critical role in the development of Kaposi's sarcoma in AIDS patients

Gayà, Antonia,d; Esteve, Annab; Casabona, Jordib; McCarthy, Jeanette Jc; Martorell, Jaumed; Schulz, Thomas Fe; Whitby, Deniseffor the EURO-SHAKS working group

Basic Science

Background: In 1994 human herpesvirus 8 (HHV-8) was identified as the causative agent of Kaposi's sarcoma (KS). Moreover, the crucial role of HLA molecules in determining susceptibility to several infections was recognized.

Objectives: To evaluate the influence of HLA-DRB1 polymorphism in KS susceptibility among HHV-8 infected AIDS patients.

Design: A matched case–control study was designed to identify possible biological and environmental risk factors for HIV associated KS. Cases were defined as any AIDS patient with a clinical diagnosis of KS and controls as any AIDS patient with an indicative disease other than KS or with CD4 cells counts < 200 × 106 cells/l, diagnosed at ± 4 months after case diagnosis. Each case was matched with two controls by sex, age and transmission category.

Methods: HHV-8 serostatus was determined by immunofluorescence assay for the latency associated antigen encoded by Orf73, ELISA for Orf73 and ELISA for the lytic antigen Orf65. DRB1 typing was carried out with a commercially available PCR–sequence specific primer assay.

Results: Comparison of marker frequencies in HHV-8 infected AIDS patients with or without KS showed a positive association between KS and HLA-DRB1 alleles containing phenylalanine at position 13 [odds ratio (OR), 2.24; P = 0.016]. A negative association was observed when the residue at the same position was glycine (OR, 0.16; P = 0.009).

Conclusion: These observations suggest a possible role for HLA-DRB1 in the development of KS in HHV-8 infected individuals with HIV co-infection. Progression to KS in HHV-8 infected AIDS patients may also depend on host factors controlling the immune response.

From the aFundació Banc de Sang i Teixits, Palma de Mallorca, bCentre d'Estudis Epidemiològics sobre l'HIV/sida de Catalunya (CEESCAT). Hospital Universitari Germans Trias i Pujol, Badalona, Spain, cSan Diego State University, San Diego, California, USA, dServei d'Immunologia, IDIBAPS, Hospital Clínic, Barcelona, Spain, the eDepartment of Medical Microbiology and Genitourinary Medicine. University of Liverpool, and fThe Institute of Cancer Research, London, UK. *See Appendix.

Correspondence to A. Gayà, Fundació Banc de Sang i Teixits de les Illes Balears, Rosselló i Caçador, 20, 07004 Palma de Mallorca, Spain.

Received: 16 September 2002; revised: 2 May 2003; accepted: 13 May 2003.

© 2004 Lippincott Williams & Wilkins, Inc.