sCD163 como biomarcador de gravidade em hanseníase e leishmaniose visceral

• Ano de defesa: 2016
• Autor(a) principal: Silva, Ricardo Luís Louzada da
• Orientador(a): Jesus, Amélia Maria Ribeiro de
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Sergipe
• Programa de Pós-Graduação: Pós-Graduação em Ciências da Saúde
• País: Brasil
• Palavras-chave em Português: Ciências da saúde; Leishmaniose visceral; Hanseníase; Neutrófilos; Macrófagos; Marcadores biológicos; CD163
• Palavras-chave em Inglês: Leishmania; Macrophages; Neutrophils; Leprosy
• Área do conhecimento CNPq: CIENCIAS DA SAUDE
• Link de acesso: https://ri.ufs.br/handle/riufs/3630

CD163, the receptor for haptoglobin–hemoglobin complex, is expressed on monocytes/macrophages and neutrophils. A soluble form (sCD163) has been associated with the M2 macrophage phenotype. M2 macrophages down-modulate the inflammatory response and has previously been described in the most severe, lepromatous (LL) clinical presentation of leprosy as well as tuberculosis. We hypothesized that sCD163 would correlate with severity of diseases caused by intracellular pathogens. Our general objective was to verify the presence of sCD163 in sera of Leprosy and Visceral leishmaniasis (VL) patients. Sera of patients with diferent clinical forms of leprosy (n = 47), and VL (n = 65) were tested for the presence of sCD163. The levels of sCD163 were compared in the diferent clinical forms of leprosy (Indeterminate - IL, Tuberculoid-TL, Boderline-BL and Lepromatous leprosy-LL). The levels of sCD163 were also compared in sera of VL patients before treatment (D0) (n = 46), and at D30 post treatment (n = 19), and also compared at D0, between patients with classical VL (n = 33) and severe VL (n = 13). High levels of sCD163 were detected in sera from leprosy patients as compared to contact controls, and confirmed the association of sCD163 with LL leprosy, finding it at elevated levels in this clinical form. ROC curves showed high sensitivity and specificity for the association between higher levels of this molecule with the most severe LL clinical form. VL patients also presented with high levels of sCD163 in sera at D0 as compared with healthy individuals, and even higher in sera from severe VL patients. Further stratification on infection and disease status revealed a clear association with clinical parameters of disease severity and clinical cure, with a direct correlation sCD163 concentration and liver and spleen sizes. ROC curves also demonstrated high sensitivity and specificity of this molecule to associate this molecule with disease severity of VL. Additionally, sCD163 concentrations reduces after treatment (D30). In vitro cultures indicated that Leishmania infection induced CD163 expression on the surface of monocyte/macrophages and neutrophils, suggesting these cells as possible sources of sCD163 in the sera. Interestingly, the association of sCD163 levels with disease status was not mirrored by levels of haptoglobin, heme-oxygenase, or arginase. Taken together, our data support the use of sCD163 as a biomarker of disease and severity in both leprosy and VL, and indicate a role of Leishmania infection in induce the expression of CD163 in macrophages and neutrophils. This data also suggest CD163 as a marker for M2 and N2, which down modulate inflammatory responses and interfere in the outcome of intracellular infections and the severity of their associated diseases.