An evaluation of p16INK4a expression in cervical intraepithelial neoplasia specimens, including women with HIV-1

Although several studies have evaluated the role of p16INK4a as a diagnostic marker of cervical intraepithelial neoplasia (CIN) and its association with disease progression, studies regarding the role of p16INK4a in human immunodeficiency virus (HIV)-infected patients remain scarce. The present study was designed to determine the potential utility of p16INK4a as a diagnostic marker for CIN and invasive cervical cancer in HIV-positive and negative cervical specimens. An immunohistochemical analysis of p16INK4a was performed in 326 cervical tissue microarray specimens. Performance indicators were calculated and compared using receiving operating characteristics curve (ROC)/area under the curve. In HIV-1-negative women, the percentage of cells that was positive for p16INK4a expression was significantly correlated with the severity of CIN (p < 0.0001). A ROC curve with a cut-off value of 55.28% resulted in a sensitivity of 89%, a specificity of 81%, a positive predictive value of 91% and a negative predictive value of 78%. HIV-seropositive women exhibited decreased expression of p16INK4a in CIN2-3 specimens compared with HIV-negative specimens (p = 0.031). The ROC data underscore the potential utility of p16INK4a under defined conditions as a diagnostic marker for CIN 2-3 staging and invasive cervical cancer. HIV-1 infection, however, is associated with relatively reduced p16INK4a expression in CIN 2-3.

Perfil de citocinas e células imunológicas em pacientes com tuberculose pleural co-infectados ou não pelo HIV / Cytokine and immune cell profile pleural tuberculosis in patients with and without HIV co-infection

Introdução: a tuberculose pleural tem uma evolução benigna, mesmo quando associada à infecção pelo HIV. Com o objetivo de compreender os mecanismos imunológicos envolvidos neste fenômeno, nós comparamos as concentrações de citocinas e subgrupos de células imunológicas no líquido e tecido pleural de pacientes com tuberculose pleural com e sem infecção pelo HIV. Material e métodos: foram incluídos 42 pacientes com o diagnóstico de tuberculose pleural dos quais 12 infectados pelo HIV. A análise imunohistoquímica do tecido pleural foi realizada em 21 pacientes utilizando os seguintes anticorpos monoclonais: anti-CD4, anti-CD8, anti-delta TCR, anti-perforina e anti-fasL. A concentração de citocinas (IL-2,IL-4, IL-10, IL-12 e IFN-) foi medida pelo método ELISA no líquido pleural de 29 pacientes. Resultados: a mediana das proporções de células CD8+ e perforina+ foi superior nos pacientes infectados pelo HIV. A proporção de células CD4+, FasL+ e delta-TCR+ foram semelhantes nos dois grupos. A IL-4 foi indetectável em todos os pacientes. Três de nove pacientes infectados pelo HIV apresentaram uma concentração de IL-2 superior a 40 pg/ml (p=0,02). Conclusões: as concentrações de IFN-, IL-10 e IL-12 foram semelhantes nos dois grupos. A citotoxicidade mediada pela perforina e a IL-2 parecem ter um papel importante na proteção contra Mycobacterium tuberculosis nos estádios iniciais da infecção pelo HIV. As células CD8+ do tecido pleural podem ser uma fonte alternativa de síntese de IFN- em pacientes com tuberculose pleural co-infectados pelo HIV.

Introduction: pleural tuberculosis (TB) has a benign course whether associated or not to HIV infection. To understand the immune mechanisms involved in this phenomenon, we compared cytokine concentrations and subsets of immune cells in the pleural fluid/tissue from patients with TB pleurisy with and without HIV co-infection. Material and methods: forty-two patients diagnosed with pleural TB were included, twelve of whom were HIV-infected. Immunohistochemical analysis of pleural tissue was performed in 21 patients with TB pleurisy with and without HIV co-infection. Material and methods: forty-two patients diagnosed with pleural TB were included, twelve of whom were HIV-infected. Immunohistochemical analysis of pleural tissue was performed in 21 patients using the following monoclonal antibodies: anti-CD4, anti CD-8, anti-delta TCR, anti-perforin and anti FasL. Cytokine (IL-2, OÇ-4, IL-10, IL-12 amd IFN-) concentration was measured by the ELISA method in the pleural fluid of 29 patients. Results: the median proportions of CD8+ and perforin + cells were higher in HIV-infected patients. The proportions of CD4+, FasL+ and delta-TCR+ cells were similar in both groups. IL-4 was undetectable in all patients. Three out of nine HIV-infected patients had IL-2 concentration ouver 40pg/ml (p=0.02). Conclusion: the concentrations of IFN-, IL-10 and IL-12 were similar in both groups. Perforin-mediated cytotoxicity and IL-2 may play an important role in protection against Mycobacterium tuberculosis in the early stages of HIV infection. Pleural CD8+ cells may be an alternative source for IFN- in HIV-infected patients with tuberculosis.