Caracterização soroepidemiológica e estudo do perfil das citocinas IL-1β, IL-2, IL-17A, MCP-1 eTGFβ1 em indivíduos com febre chikungunya no estado do Ceará, Brasil

Abstract

Chikungunya fever is an arbovirus that has had a major impact on public health in Brazil, as it is transmitted by Aedes aegypti, a mosquito widely spread in the country, and due to its high morbidity, evolving with chronic arthritis in many infected people. The immunological mechanisms that produce these symptoms as well as the protection mechanisms have not been fully elucidated yet. Thus, in this study, the seroepidemiological profile was characterized and the response of cytokines IL-1β, IL-2, IL-17A, MCP-1 and TGF-β1 was evaluated in individuals with chikungunya fever in the acute, post-acute and chronic phases, and in the seropositivity groups for anti-CHIKV antibodies. It was a descriptive and cross-sectional study, with collection of sociodemographic data and analysis of serum samples from 351 patients with chikungunya fever in 2017 in the state of Ceará, Brazil. Serology for antiCHIKV and anti-DENV antibodies and quantification of serum cytokines were performed using the ELISA method. All data were analyzed and modeled using the Stata® 15 software, using the Mann-Whitney, Kruskal-Wallis and Pearson chi-square statistical tests, with significance of p <0.05. In the study, predominant individuals were born in Fortaleza (54.99%), female (78.92%) and aged between 18 and 69.9 years (69.05%). Subjects above the median age (51.73) were more frequent in the post-acute and chronic phases (p = 0.033). Female subjects had a longer duration of symptoms when compared to male subjects (p = 0.0321). The medians of age by seropositivity groups for anti-CHIKV were: 48.02 for IgM + IgG-; 53.44 for IgM + IgG + and 59.45 for IgM-IgG +. There was a predominance of females in all groups. In the group with IgM + IgG-, 50.00% of the subjects were in the acute phase and the other 50.00% in the post-acute phase; in the group with IgM + IgG +, 53.41% were in the post-acute phase; in the group with IgM-IgG +, 70.83% were in the chronic phase. 7.98% of IgM anti-CHIKV / IgM anti-DENV codetection was found. Individuals with IgM-IgG + had higher levels of IL-2 (p = 0.0317) compared to the other groups. In the chronic phase of the disease, the subjects had higher levels of TGF-β1 compared to the other phases. Subjects with IgM + IgG + and IgM- IgG + showed higher levels of TGF-β1 (p = 0.0121) compared to those with IgM + IgG-. No significant difference was observed when comparing the levels of IL-1β, IL-17A and MCP-1 in the disease phases and in the seropositivity groups for antiCHIKV antibodies. A decrease in the MCP-1 / TGF- β1 ratios was observed with progression to the chronic phase of the disease (p = 0.0203), also in the group with IgM- IgG +, when compared to the other groups (p = 0.0038). Thus, it was possible to conclude that female subjects affected by chikungunya and aged over 51.73 years had longer duration of symptoms and that high levels of IL-2 and TGF-β1 were related to the group with IgM-IgG+ and the chronic phase of the disease, suggesting that the immunological characteristics of CHIKF chronicity are associated with changes in immunotolerance switches.