RESUMO
Cervical cancer incidence worldwide exceeds half a million new cases per year. The human papillomavirus (HPV) being the major causative agent of CC uses a variety of strategies to evade immune surveillance, where the immune status varies amongst individuals. This immune evasion altered by HPV is reflected in persistent infections, causing the evolution of cervical neoplasia. The role of the immune system in viral recognition and elimination is of extreme relevance in the development of CC. The interactions of the HLA-E ligand in the target cell along with CD94/NKG2 receptors, which are expressed predominantly, but not exclusively, on NK cells' surface, are responsible for activating or inhibiting cytotoxic activity according to their function. The engagement between HLA-E and CD94/NKG2 molecules is one of the fundamental surveillance mechanisms in patients with CIN I, II and III, where HLA-E expression increases significantly, especially in HPV 16 and 18 infections. Higher HLA-E expression was observed in most histopathological types of CC, and at the same time was correlated to best survival of the patient. This review aims to summarize and discuss the immunological role of HLA-E in the context of HPV infection and immune system evasion, and the oncogenic process of cervical cancer.
Assuntos
Antígenos de Histocompatibilidade Classe I/imunologia , Evasão da Resposta Imune , Papillomaviridae/imunologia , Infecções por Papillomavirus/imunologia , Suscetibilidade a Doenças , Feminino , Antígenos de Histocompatibilidade Classe I/genética , Humanos , Vigilância Imunológica , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/virologia , Neoplasias do Colo do Útero/etiologia , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/patologia , Antígenos HLA-ERESUMO
Human papillomavirus (HPV) can induce cervical intraepithelial neoplasias (CIN) grades 1, 2 and 3. Untreated, these lesions may progress to cervical cancer (CC) which is the third most common cancer in women worldwide. HLA-G plays an immunotolerant role in the immune response. The aim of this study was to characterize the configuration of SNPs located at the distal promoter of HLA-G in patients with CIN2 and CIN3 and control women. The study sample was composed of 207 women as follows: 73 diagnosed with CIN2 lesions, 56 with CIN3 and 78 healthy control women. Genotyping was performed by sequence base typing. Eleven haplotype configurations subdivided in two main haplogroups (H1dist and H2dist), were characterized and compared between patients and controls. The haplotypes H1.1Dist (GAGAACGC) and H2.1Dist (AGGTACAC) were more frequent in Euro-Descendants as well as in Brazilian Mixed. Nevertheless, the haplotype H2.1Dist standed out as a susceptibility haplotype in Brazilian Mixed patients while the H1.1Dist presented a protector effect in this same ethnic group. Whether such LCR haplotype configurations can impact on HLA-G gene expression levels in women who developed cervical intraepithelial neoplasia is still unknown and it is of utmost importance that more investigation on this field be pursued.
Assuntos
Antígenos HLA-G/genética , Haplótipos , Sequências Reguladoras de Ácido Nucleico/genética , Displasia do Colo do Útero/genética , Neoplasias do Colo do Útero/genética , Adolescente , Adulto , Sequência de Bases , Feminino , Frequência do Gene , Genótipo , Humanos , Pessoa de Meia-Idade , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/genética , Projetos Piloto , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas/genética , Neoplasias do Colo do Útero/complicações , Adulto Jovem , Displasia do Colo do Útero/complicaçõesRESUMO
OBJECTIVE: The aim of the present study was to investigate a broad spectrum of autoantibodies in patients with endemic pemphigus foliaceus (EPF)-fogo selvagem-and to determine the possible association between EPF and other autoimmune diseases. MATERIALS AND METHODS: Indirect immunofluorescence was used to test 120 patients with EPF and 200 healthy controls for the presence of the following autoantibodies: anti-desmoglein-1 (APF), anti-neutrophil cytoplasmic (ANCA), anti-smooth muscle (SMA), anti-mitochondrial (AMA), anti-nuclear (ANA), anti-liver kidney microsomal (LKM), anti-gastric parietal cells (GPCA) and anti-thyroid microsome (TMA). RESULTS: APF antibodies were detected in 62.5% of the patients (75/120), ANA and SMA in 0.8% (1/120), and TMA in 1.6% (2/120). None of the patients was positive for ANCA, AMA, LKM or GPCA. In the control group, a positivity of 2% was observed for SMA (4/200), 1.5% for TMA (3/200), and 0.5% (1/200) for ANA and GPCA. None of the controls was positive for APF, LKM, AMA or ANCA. CONCLUSIONS: The prevalence of the autoantibodies ANA, SMA, AMA, GPCA, LKM and ANCA in patients with EPF was similar to that observed in the control group. No association with clinical or laboratory manifestations of other concomitant autoimmune diseases was observed in EPF patients. These results confirm the concept that EPF is an organ-specific autoimmune disease.