Tuberculosis (TB) is still one of the top ten leading causes of death in the world. Compared to other Baltic and Eastern European countries, TB incidence (24.8 new cases per 100 000 people in 2017) in Latvia is relatively high. One of the regions with the highest TB incidence is Latgale (31.1 cases per 100 000 people). The aim of this pilot study was to identify markers of genetic predisposition to TB in Latgale. The study included 26 patients (16 males and 10 females) aged between 18 and 85 with bilateral TB pneumonia and without HIV infection. HLA typing was performed in HLA-DRB1, -DQA1, and -DQB1 loci by a polymerase chain reaction with low resolution sequence-specific primers. HLA-DRB1*07 and HLA-DRB1*11 alleles were identified as risk alleles for TB. HLA-DRB1*15 allele was a protective allele. Due to the limitations of this exploratory study, a broader study needs to be conducted to revealing specific risk and protective HLA Class II alleles for TB in the subpopulation of Latgale.
This study aimed to detect the expression level of ORAI1 and STIM1 genes in blood of patients with bilateral pulmonary tuberculosis (TB) in comparison with the control group. Both genes encode proteins providing store-operated Ca 2+ entry (SOCE) into the cells, including immune cells, to activate transcriptional factors for producing cytokines and inflammation-restricting proteins. The study included 45 patients with confirmed TB, aged 20 to 86, and 35 volunteers, aged from 21 to 73, without active TB infection. The expression of ORAI1 and STIM1 genes in blood was performed by real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR). Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was used as the referent gene. Inflammation was assessed by levels of interferon γ (IFN-γ) and interleukin 18 in serum (ELISA method). The results showed lower expression of ORAI1 in blood and higher levels of in serum of TB patients than that of the control group and no differences in expression of the STIM1 gene. It indicates some impairment in the SOCE mechanism of immune cells, which is associated with TB.
Antiretroviral therapy (ART) aims at suppressing viral replication and strengthening immune system in patients with HIV-1. Human Leukocyte Antigens (HLA) are among factors responsible for effectiveness of ART. The aim of this study was to determine the effect of HLA Class II alleles on the response to long-time ART, assessed by a change in CD4+ T-cell count in relation to viral load. The sample included 69 patients (17 females and 52 males) aged 20 to 50 with HIV-1 infection, who were undergoing ART in the Latvian Centre of Infectious Diseases. The median period of observation was 5.7 years. CD4+ T-cell count and viral load were analysed at the baseline and end of the period of observation. HLA typing was performed by polymerase chain reaction with low resolution sequence specific primers. Multiple hierarchical linear regression analysis confirmed that an increase in HIV-1 viral load was associated with a decrease in the level of CD4+ T-cell count. In addition, HLA-DRB1*04 and HLA-DQB1*06:01 alleles contributed negatively to the level of CD4+ T-cell count.
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