BackgroundImmunosenescence is associated with several changes in adaptive and innate immune cells. Altered cytokine production is among the most prominent of these changes. The impact of age-related alterations on cytokine global profiles produced by distinct populations of leukocytes from healthy Brazilian individuals was studied. We analysed frequencies of cytokine-producing lymphocytes and innate immune cells from individuals at several ages spanning a lifetime period (0–85 years).ResultsHealthy adult individuals presented a balanced profile suggestive of a mature immune system with equal contributions of both innate and adaptive immunity and of both categories of cytokines (inflammatory and regulatory). In healthy newborns and elderly, innate immune cells, especially neutrophils and NK-cells, contributed the most to a balanced profile of cytokines.ConclusionsOur results support the hypothesis that ageing is not associated with a progressive pro-inflammatory cytokine production by all leukocytes but rather with distinct fluctuations in the frequency of cytokine-producing cells throughout life.Electronic supplementary materialThe online version of this article (doi:10.1186/s12979-017-0084-5) contains supplementary material, which is available to authorized users.
In this study, strategies for serum biomarker assessment were developed for therapeutic monitoring of HCV patients. For this purpose, serum chemokine/cytokine levels were measured by cytometric-bead-array in HCV patients, categorized according to immunotherapy response as: non-responder/NR, relapser/REL and sustained-virologic-responder/SVR. The results demonstrated an overall increase of serum chemokine/cytokine levels in HCV patients. In general, therapeutic failure was associated with presence of a predominant baseline proinflammatory pattern with enhanced CCL5/RANTES, IFN-α, IFN-γ along with decreased IL-10 levels in NR and increased IL-6 and TNF in REL. SVR displayed lower baseline proinflammatory status with decreased CXCL8/IL-8, IL-12 and IL-17 levels. The inability to uphold IFN-α levels during immunotherapy was characteristic of NR. Serum chemokine/cytokine signatures further support the deleterious effect of proinflammatory baseline status and the critical role of increased/persistent IFN-α levels to guarantee the sustained virologic response. The prominent baseline proinflammatory milieu observed in NR and REL yielded a restricted biomarker network with small number of neighborhood connections, whereas SVR displayed a network with integrated cytokine connectivity. Noteworthy was that SVR presented a shift towards a proinflammatory pattern upon immunotherapy, assuming a pattern similar to that observed in NR and REL at baseline. Moreover, the immunotherapy guided REL towards a profile similar to SVR at baseline. Analysis of baseline-fold changes during treatment pointed out IFN-α and TNF as high-performance biomarkers to monitor immunotherapy outcome. This knowledge may contribute for novel insights into the treatment and control of the continuous public health threat posed by HCV infection worldwide.
Background: Identifying patients with hepatitis C virus (HCV) infection and enhancing the cascade of care are essential for eliminating HCV infection. This study aimed to estimate the prevalence of positive anti-HCV serology in Brasilia, Brazil, and evaluate the efficiency of the cascade of care for HCV-positive individuals.Methods: This cross-sectional study analyzed 57,697 rapid screening tests for hepatitis C in individuals aged > 40 years between June 2018 and June 2019. HCV-positive patients were contacted and scheduled to undergo the HCV RNA viral test, genotyping, and transient elastography.Results: The prevalence of positive serology was 0.27%. Among 161 patients with positive anti-HCV serology, 124 (77%) were contacted, 109 (67.7%) were tested for HCV RNA viral load, and 69 (42.8%) had positive results. Genotype 1 (75%) was the most prevalent genotype. Among 65 patients (94.2%) who underwent transient elastography, 30 (46.2%) presented with advanced fibrosis. Additionally, of the 161 patients, 55 (34.1%) were referred for treatment, but only 39 (24.2%) complied, with 36 (22.4%) showing sustained virological response. By the end of the study, 16 patients were still awaiting to receive medication. Conclusions:The prevalence of HCV-positive patients was low in Brasilia, and the gaps in the cascade of care for these patients were significantly below the targets of HCV infection elimination. This study opens new avenues for eliminating HCV infection and suggests that partnerships with clinical laboratories to conduct anti-HCV tests are a useful strategy to improve HCV diagnosis.
O VÍRUS DA HEPATITE C É A PRINCIPAL CAUSA DE HEPATITE CRÔNICA NO MUNDO. A INFECÇÃO CRÔNICA PELO HCV É, PREDOMINANTEMENTE, ASSINTOMÁTICA. O DIAGNÓSTICO DE HEPATITE C DEVE SER BUSCADO EM TODOS OS PACIENTES COM ELEVADOS NÍVEIS DE TRANSAMINASES NO SANGUE, COM DOENÇA HEPÁTICA CRÔNICA SEM ETIOLOGIA DEFINIDA E AQUELES QUE APRESENTEM UMA HISTÓRIA DE ELEVADO RISCO PARA TRANSMISSÃO DA DOENÇA. A TERAPIA ANTIVIRAL OBJETIVA À CURA DA HEPATITE C ATRAVÉS DA ELIMINAÇÃO DO VÍRUS. A ANEMIA É UM EFEITO ADVERSO USUAL DURANTE O TRATAMENTO COM INTERFERON PEGUILADO E RIBAVIRINA. O ESTUDO OBJETIVA OBSERVAR A TAXA DE RESPOSTA VIROLÓGICA SUSTENTADA E SUA CORRELAÇÃO COM A ANEMIA SECUNDÁRIA AO USO DESSES MEDICAMENTOS. CONCLUIU-SE QUE, APÓS 12 SEMANAS DE TRATAMENTO, A MÉDIA DA HEMOGLOBINA FOI ESTATISTICAMENTE MENOR NO GRUPO QUE OBTEVE RESPOSTA VIROLÓGICA SUSTENTADA, E A QUEDA DA HEMOGLOBINA EM RELAÇÃO À BASAL FOI MAIOR NO GRUPO QUE RESPONDEU AO TRATAMENTO. COMO A DOSAGEM DA HEMOGLOBINA É UM EXAME DE BAIXO CUSTO E MANDATÓRIO PARA A AVALIAÇÃO PRÉ E PER TRATAMENTO, SUA UTILIZAÇÃO COMO PROGNÓSTICO DE RVS DEVE SER ESTIMULADA.
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