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.
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.


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


METHODS
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 x 10 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).


CONCLUSIONS
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.
Gayà
Antoni
A
Fundació Banc de Sang i Teixits, Palma de Mallorca, Spain.
Esteve
Anna
A
Casabona
Jordi
J
McCarthy
Jeanette J
JJ
Martorell
Jaume
J
Schulz
Thomas F
TF
Whitby
Denise
D
D017088:AIDS-Related Opportunistic Infections / Q000235:genetics* / Q000276:immunology; D000328:Adult; D000595:Amino Acid Sequence; D018791:CD4 Lymphocyte Count; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D019288:Herpesvirus 8, Human / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics* / Q000502:physiology; D012307:Risk Factors; D012514:Sarcoma, Kaposi / Q000235:genetics* / Q000276:immunology
D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains