Investigação epidemiológica e relação entre polimorfismos genéticos nos antígenos leucocitários humanos (HLA) classe II (DRB1* e DQB1*) em indivíduos com tuberculose pulmonar, extrapulmonar e sem tuberculose no Estado do Amazonas

Abstract

Tuberculosis (TB) is an infectious and transmissible disease caused by mycobacteria of the Mycobacterium tuberculosis complex. The most common clinical form is pulmonary tuberculosis (PTB), however other organs and/or systems can be affected, causing extrapulmonary tuberculosis (ExPTB). Despite being an ancient disease, tuberculosis remains as a major public health problem worldwide. In Brazil, in 2022, there were more than 78,000 new cases of TB, approximately 2.2 deaths/100,000 inhabitants due to TB. In that same year, Amazonas recorded 84.1 TB cases/100,000 inhabitants and 4.0 deaths caused by TB/100 thousand inhabitants, the highest rates of the disease in the country. These data encourage research in the field of immunology, given that most individuals infected with M. tuberculosis can control the infection and less than 10% progress to active disease. Furthermore, TB has a broad clinical spectrum, suggesting that immunogenetic factors, such as HLA - Human Leukocyte Antigen (human leukocyte antigen) class II molecules, may be involved in the evolution of the disease. These molecules are constitutively present in antigen-presenting cells and form complexes with peptides that will be presented to T helper (Th) lymphocytes. In TB, the immune response by Th1 lymphocytes is important for controlling the infection. For this reason, the objective of this research was to investigate the distribution of HLA-class II gene alleles (DRB1 and DQB1) in individuals with TB. This study included 519 participants, 195 were PTB patients, 67 ExPTB and 257 healthy controls, all recruited from a reference center in Amazonas. Sputum samples made it possible to identify the mycobacteria involved, while blood samples made it possible to evaluate HLA alleles. The results revealed that HLA-DRB1*04 was the most frequent allele in PTB patients (23.8%) when compared with the control group (14.6%) (p = 0.0005; OR 1.833; 95%CI 1.305 to 2.556) and with ExPTB patients (12.7%) (p = 0.009; OR 2.155; 95%CI 1.257 to 3.847). HLA-DRB1*07 was more frequent in the control group (10.7%) when compared with PTB patients (4.6%) (p = 0.0014; OR 0.404; 95%CI 0.234 to 0.686). As for DQB1 alleles, HLA-DQB1*02 was the most frequent in the control group (15.2%) when compared with PTB patients (10.0%) (p = 0.0281, OR 0.621; 95% CI 0.408 to 0.942); while HLA-DQB1*0302 was the most frequent in PTB patients (22.1%), compared with controls (13.0%) (p = 0.0005; OR 1.887; 95%CI 1.330 to 2.661) and with ExPTB patients (11.9%) (p = 0.0150; OR 2.086; 95%CI 1.188 to 3.624). There was no association between HLA and the ExPTB clinical form, but this group had the highest number of individuals who were blank/homozygous for HLA-DRB1 (7.5%) (p = 0.0415; OR 2.510; 95% CI 1.145 to 5.768). Finally, in the assessed groups, individuals expressing HLA-DRB1*04 and DQB1*0302 alleles are more likely to develop the pulmonary clinical form of TB. On the other hand, the HLA-DRB1*07 and HLA-DQB1*02 alleles seem to have a protective effect only for the PTB form.