HIV asociētās tuberkulozes imunoģenētiskie aspekti

Translated title of the contribution: The Immunogenetic Aspects of HIV-Associated Tuberculosis

Inga Ažiņa

Research output: Types of ThesisDoctoral Thesis


Tuberculosis is an infectious disease, which develops frequently during HIV-1 infection and increases immunodeficiency accelerating one’s death. Diagnostics of HIV-associated tuberculosis is an important problem, because of losing typical clinical and roentgenological symptoms of the mycobacterial infection under pronounced immunodeficiency. In Latvia, the number of patients with HIV-associated tuberculosis increased simultaneously with increasing number of patients with HIV-1. Previous studies demonstrated that development of tuberculosis in patients with HIV-1 is impacted not only by HIV-1 virus activity but also by allelic variants of genes’ class II of the major histocompatibility complex and by change in an immune reaction. At the same time, there is no clarity regarding the contribution of each factor explaining development of tuberculosis in patients with HIV-1 infection. Therefore, the aim of the doctoral thesis (The Immunogenetic aspects of HIV-associated tuberculosis) was to investigate the relationship of HLA Class II alleles with markers of immunological status and HIV-1 viral load in patients with HIV-associated tuberculosis in Latvia. The research was performed in Riga East University Hospital, Latvian Centre of Infectious Disease between 2012 and 2016. The research sample consisted of 258 patients. The first group included 158 HIV-associated tuberculosis patients at age from 23 to 59 with HIV-1 infection and confirmed active tuberculosis (HIV-1/TB group). The second group included 100 patients at age from 18 to 48 with HIV-1 infection without tuberculosis (HIV-1 group). All patients with HIV-1 infection and tuberculosis received antiretroviral therapy and anti-tuberculosis therapy according to Guidelines for treatment of HIV-1 infected adults in Europe. In order to assess genetic predisposition, HLA class II (HLA-DRB1*, HLA-DQA1*, and HLA-DQB1*) typing was performed by real time polymerase chain reaction. In order to assess immunological status, CD4+ cells count, levels of three interleukins (IL-1β, IL-10, IL-18) and of interferon-γ (IFN-γ) were detected in peripheral blood. HIV-1 viral activity was represented by viral load (HIV RNS). The results of immunogenetic analysis revealed five protective and four risk alleles associated with development of HIV-associated tuberculosis. In patients with HIV-1, development of tuberculosis associates with HLA-DQA1*01:03, HLA-DQA1*05:01, HLA-DQB1*02:01, and HLA-DQB1*04:01 alleles. Resistance against tuberculosis associates with HLA-DRB1*01, HLA-DQA1*01:01, HLA-DQA1*01:02, HLA-DQB1*05:02, and HLA-DQB1*06:02 alleles. The results of a regression analysis demonstrate that the number of CD4+ T lymphocytes is the main factor associated with the development of tuberculosis coinfection among factors included into analysis. A correlative analysis indicate that the number of CD4+ cells is related to viral load that is in accordance with the previous studies. In addition, the number of CD4+ cells correlates with risk and protectives alleles. Within a group of HIV-associated tuberculosis, correlations between alleles, levels of cytokines, and the number of CD4+ T lymphocytes confirm an impact of alleles on immunological reaction. Some alleles of HLA class II can have an effect on time of tuberculosis development. In addition to revealed effect of CD4+ T lymphocytes, this study revealed the relationship between exitus letalis and the level of IL-18 (higher in the group of patients who were alive in a certain time point). In summary, the results provide more detailed view of genetic factors in the development of HIV-associated tuberculosis. The findings can be also helpful in the early assessment of the patient’s status and assigning a therapy.
Translated title of the contributionThe Immunogenetic Aspects of HIV-Associated Tuberculosis
Original languageLatvian
  • Rozentāle, Baiba, First/Primary/Lead supervisor
  • Lejnieks, Aivars, First/Primary/Lead supervisor
Place of PublicationRiga
Publication statusPublished - 2017
Externally publishedYes


  • Medicine
  • Subsection – Infectology
  • Doctoral Thesis

Field of Science*

  • 3.2 Clinical medicine

Publication Type*

  • 4. Doctoral Thesis


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