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Basic Science

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, Denisef; for the EURO-SHAKS working group

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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.

© 2004 Lippincott Williams & Wilkins, Inc.


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