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BIBTEX RIS

CD11c+CD123Low Dendritic Cell Subset and the Triad TNF-α/IL-17A/IFN-γ Integrate Mucosal and Peripheral Cellular Responses in HIV Patients With High-Grade Anal Intraepithelial Neoplasia

2014; Lippincott Williams & Wilkins; Volume: 68; Issue: 2 Linguagem: Inglês

10.1097/qai.0000000000000412

ISSN

1944-7884

Autores

Adriana Gonçalves Daumas Pinheiro Guimarães, Allyson Guimarães Costa, Olindo Assis Martins‐Filho, João Paulo Diniz Pimentel, Danielle Alves Gomes Zauli, Vanessa Peruhype-Magalhães, Andréa Teixeira‐Carvalho, Samantha Ribeiro Béla, Marcelo Antônio Pascoal-Xavier, Jordana Grazziela Coelho-dos-Reis, Josilene S. Abranches, José J. P. Guimarães, Adriana Malheiro, Luiz C. L. Ferreira,

Tópico(s)

Immunotherapy and Immune Responses

Resumo

The incidence of anal cancer has increased over the past 25 years, and HIV/HPV coinfection is the most important risk factor for anal squamous cell carcinoma. In this study, we demonstrated that the evaluation of systemic and compartmentalized anal mucosa immune response is relevant to differentiating HIV(+) patients at risk of anal intraepithelial neoplasia (AIN).A systems biology approach was used to integrate different immunological parameters from anal mucosal tissue and peripheral blood assessed by phenotypic and intracytoplasmic analysis of lymphocytes and dendritic cell subsets.Our data demonstrated that anal mucosal mononuclear cells from AIN(+)HIV(+) patients showed a robust capacity in producing proinflammatory/regulatory cytokines, mainly mTNF-α > IL-4 > IL-10 > IL-6 = IL-17A. Mucosal TNF-α/IFN-γ/IL-17A are selective high-grade squamous intraepithelial lesion (HSIL)-related biomarkers. Higher levels of circulating CD11cCD123cells and CD1a cells along with elevated levels of IFN-γCD4 T cells are major features associated with HSIL in AIN(+)HIV(+) patients. Regardless of the presence of AIN, HIV(+) patients presented a complex biomarker network, rich in negative connections. Among those patients, however, HSIL+ patients displayed stronger positive links between peripheral blood and anal mucosa environments, exemplified by the subnet of IL-17A/TNF-α/CD4IFN-γ/CD11cCD123 cells.The significant association between HSIL and the levels of TNF-α/IL-17A/IFN-γ along with the different subsets of DCs present in the anal mucosa milieu should be studied in more detail as a way to identify and categorize HIV(+) patients vis à vis the high risk of anal cancer outcome.

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