GENETIC VARIATIONS OF HLA DRB1 ALLELES IN CEREBRAL TOXOPLASMOSIS IN PATIENTS WITH HIV INFECTION
DOI:
https://doi.org/10.11603/1681-2727.2018.2.9021Keywords:
HIV infection, opportunistic diseases, cerebral toxoplasmosis, HLA DRB1 alleles.Abstract
SUMMARY. Toxoplasmosis of the central nervous system is one of the most common causes of brain damage in AIDS patients. The polymorphism of the HLA DRB1 loci is associated with protection against HIV-1 and can affect the development of opportunistic diseases.
The aim of the work is to study the variations of HLA DRB1 alleles in cerebral toxoplasmosis and compare them with the data of patients with other opportunistic diseases in the 4th clinical stage of HIV infection to determine the protective capabilities.
Patients and methods. The study involved 70 patients with HIV infection and opportunistic diseases, indicative for 4th clinical stage, aged 24 to 61 years, among whom 41 (58.6 %) were males and 29 (41.4 %) females.
66 (94.3 %) patients were discharged from the hospital with improvement, 4 (5.7%) patients died due to the disease.
Patients were divided into two groups: the main group consisted of 23 patients (32.9 %), with brain toxoplasmosis, confirmed by detection of Toxoplasma gondii DNA in the cerebral spinal fluid, serological studies and characteristic features in a series of tomograms, and in dead patients, studies of autopsy material of brain tissue. The comparison group included 47 patients (67.1 %) who had other opportunistic diseases.
The DRB1 alleles genotyping was performed by PCR variant of Sequence Specific Primers (PCR-SSP). The study was carried out by sets of «HLA-DNA-TECH» for the typing of the genes DRB1 produced by «DNA-Technology» (Russia).
The statistical processing of the study results was conducted using STATISTICA v.6.1® application package.
Results. The analysis of variations of alleles of the DRB1 locus of the HLA class II system in 70 patients with the 4th clinical stage of HIV infection showed that in most cases allele loci DRB1*01 (21.4 %), DRB1*04 (18.6 %), DRB1*07 (25.7 %), DRB1*11 (35.7 %), DRB1*13 (18.6 %), DRB1*15 (17.1 %), DRB1*16 (21.4 %) were detected. The alleles DRB1*02, DRB1*05, DRB1*06, DRB1*09, DRB1*18 were not detected in any case.
There was the tendency determined of increased number of carriers of DRB1*01 (30.4 %), DRB1*15 (26.1 %), DRB1*16 (30.4 %) alleles within the patients with toxoplasmosis in comparison to other opportunistic diseases – 17.0 %, 12.8 % and 17.0 %, respectively. At larger groups of observation the difference between these indicators can reach a critical level of statistical significance (p<0.05) for prediction of cerebral toxoplasmosis development. At the same time, the risk of toxoplasmosis development among HIV-positive patients with DRB1*13 alleles was significantly lower than in other diseases (rs=-0.26; p<0.05). Thus, the allele of the DRB1*13 gene was found in 1 (4.3 %) of the patient with toxoplasmic infection and in 12 (25.5 %) patients with opportunistic diseases of another etiology (p=0.048 FET), indicating a possible protective effect of the identified alleles.
The performed analysis of variations of the DRB1 alleles of the HLA class II system with toxoplasmosis separately, depending of sex, showed the presence of probable associations with toxoplasmosis in females, carriers of alleles of the DRB1*16 gene (46.2 %; p<0.01), while in males this variant was more often associated with opportunistic diseases of another etiology (25.8 % vs. 10.0 %; p>0.05). The opposite tendencies were established for DRB1*04 alleles: they were found only in female patients without toxoplasmic infection (31.3 %; p<0.05); in males, on the contrary, DRB1*04 allelic carriers were more commonly seen in patients with toxoplasmosis (30.0 % vs. 16.1 %; p>0.05).
Conclusions. Expression of the HLA-DRB1 variant has definitive connection to sex, influences progression of HIV and development of toxoplasmosis. The tendency to increase of DRB1*01 (30.4 %), DRB1*15 (26.1 %), DRB1*16 (30.4 %) alleles carriers among patients with toxoplasmosis suggests increased susceptibility to toxoplasmosis and the need to intensification of prophylaxis activities in this group. The lower risk of toxoplasmosis development among HIV-positive patients with DRB1*13 alleles than of other diseases (rs=-0.26; p<0.05) indicates the protective effect of this genetic variant regarding toxoplasmosis.
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