Dados do Trabalho

Título

High levels of IP-10 are associated with immune activation, low CD4+ T cell counts and parasite load in visceral leishmaniasis patients: implications to severity and relapses

Introdução

Visceral leishmaniasis (VL) is an infectious disease caused by Leishmania (L.) infantum in Brazil. Depletion of CD4+T lymphocytes, polyclonal activation, microbial translocation, and cytokine storm are involved in immunopathogenesis and have been investigated for involvement in the VL severity. Nevertheless, the factors related to the clinical remission and relapses remain unclear. IP-10, a chemokine induced by IFN-γ and LPS, have been related to prognosis in several infectious diseases, as HIV and malaria.

Objetivo (s)

Our aim was to assess IP-10 levels in VL patients and verify if it were associated with different clinical outcomes or severity in VL.

Material e Métodos

Thus, fifteen VL patients recruited from Hospital Eduardo de Menezes (BH-MG) were evaluated since active phase until 12 months post-treatment (mpt). Ten healthy controls (HC) were included. IP-10 levels were evaluated by Luminex assay. Absolute CD4+T counts and activated T cells were evaluated by flow cytometry. Parasite loads were assessed by qPCR.

Resultados e Conclusão

High levels of IP-10 were observed in active VL, with progressive decrease throughout the clinical follow-up (p<0.05). Despite this, IP-10 levels remain significantly higher in VL patients up to 12mpt when compared to HC. Similarly, high percentages of activated CD4+/CD8+T cells were observed in VL patients throughout the follow-up. Besides, low counts of CD4+T cells were observed in VL patients at early stages of follow-up (p<0.05), reaching values close to HC from 6mpt. Curiously, IP-10 levels were negatively correlated with CD4+T cells counts and positively correlated with activated CD4+/CD8+ T-cells and parasite load. Subsequently, patients were stratified according to VL relapses (non-relapsing [NR-VL]: n=10; and relapsing [R-VL]: n=5). Interestingly, IP-10 levels were significantly higher in NR-VL patients when compared to R-VL in active disease. These levels were negatively correlated with the number of VL episodes. Our results suggest that IP-10 may be involved in VL pathogenesis, which may be implicated in relapses and severe disease.

Palavras-chave

visceral leishmaniasis, IP-10, clinical outcome

Agradecimentos

FAPERJ, CNPq, IOC/FIOCRUZ, IFRJ