Research of HLA II Class DRB1, DQA1, DQB1 Genetic Markers in Patients with HIV Infection and AIDS

Abstract

Aims: To find out the most frequent associations of the HLA II class loci DRB1*, DQA1*, DQB1* with the HIV/AIDS infection. Place and Duration of Study: The study took place in The Laboratory of Clinical Immunology and Immunogenetics (LCII) of Riga Stradiņš University (RSU), Riga, Latvia, Riga Eastern Clinical University Hospital, “Infectology Centre of Latvia”, between May 1991 and December 2004. Methodology: We analysed the medical documentation of 2500 patients and included 1180 (888 men, 292 women, 185 of them in AIDS phase) HIV infected patients. Genomic DNA was extracted from the blood with phenol-chloroform extraction method. Low-resolution HLA typing for HLA- DRB1*; DQB1*; DQA1* was performed by polymerise chain reaction (PCR) with amplification with sequence-specific primers (SSP). PCR products were separated on 3% agarose, the amplified bands were visualized, and the HLA-DRB1; DQA1; DQB1 type was deduced. Results: Genetic markers of immunologic alleles upon development of HIV infection – HLA-DRB1*03(17:01); 05(11:01); 07:01; HLA-DQA1*01:01; 02:01; 03:01; 06:01; HLA-DQB1* 03:02; 05:01; 03:03; 03:04, as well as resistance markers connected with slow development of HIV infection – HLA-DRB1*01:01; 04:01; 06(13:01); HLA-DQA1*01:03; 04:01; 05:01; HLA-DQB1*03:01; 03:03; 04:01-2; 06:01; 06:02-8 are located in different groups of patients. High risk markers in case of HIV infection development belonging to the following groups of alleles: HLA-DRB1*03(17:01), DRB1*05(11:01), DQA1*01:01; 03:01 un DQB1*05:01; 03:02, as well as three-loci haplotypes HLA-DRB1*03(17:01)/ DQB1*05:01/ DQA1*01:01; HLA-DRB1*05(11:01)/DQB1*03:01/ DQA1 *05:01; DRB1*01:01/DQB1*03:02/ DQA1*03:01 and DRB1*01:01/DQB1*05:01/DQA1*01:01 are determined. Resistance to HIV infection development forms in the following groups of alleles: HLA-DRB1*01:01; 06(13:01), HLA-DQB1* 03:01; 06:02-8; HLA-DQA1*01:02; 01:03, as well as in haplotypes HLA- DRB1*01:01/DQB1*06:02-8/DQA1*01:02;HLA-DRB1*06(13:01)/DQB1*06:02-8/DQA1*01:02; HLA-DRB1*01:01/DQB1*03:01/DQA1*01:02; and HLA-DRB1*06(13:01)/DQB1*06:02-8/ DQA1*01:02 in different groups of HIV/AIDS patients. Conclusion: The prevalence of genes DRB1; DQA1; DQB1 and DRB1-DQA-DQB1 combinations in the five groups of HIV infected patients have been established. Comparative analysis was performed also in the group of healthy donors (control group). The role of the main histocompatibility complex has been established, it enables marker functions and that can be used in the additional prognostic diagnostics in case of HIV infection. The obtained results testify that upon the identification of HIV genes it is possible to understand the molecular mechanisms in case of progression of AIDS syndrome complex; this possibly can be beneficial for the determination of the clinical results of infected patients.