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1.
Immunology ; 131(1): 89-98, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20545782

RESUMO

Cervical neoplastic lesions are associated with infection by high-risk human papilloma-viruses (HPV). The two genotypes most frequently found in the lesions are HPV-16 and HPV-18 with a prevalence of 50-60% and 15-18%, respectively. The E6 and E7 viral oncoproteins are involved in the transformation process and represent foreign antigens for the host. We previously reported that anti-HPV-18 E6 CD4(+) T cells are present in patients with high-grade HPV-18-expressing cervical lesions but also in 50% of the total consecutive patients tested, independently of the HPV type carried. These results indicated that HPV-18 E6 is immunogenic and suggested that all responsive patients, irrespective of the HPV expressed, had encountered HPV-18 and cleared the infection. Here, we investigated anti-HPV-18 E7 CD4(+) T-cell immunity in a cohort of 23 HPV-18 E6-responsive patients. We found that, although E7-specific CD4(+) T cells were present in all women, a robust T helper type (Th1)/Th2 type response against E7 was associated with HPV-18-negative status, suggesting that indeed these patients might have cleared the virus. In agreement with this hypothesis, we found strong anti-E7 CD4(+) T-cell immunity in 20% of 24 healthy donors without evidence of disease. In contrast, a robust Th1/Th2 type response against E6 but not E7 correlated with a lack of disease relapse and/or infection recurrence but did not discriminate between HPV-18-positive and HPV-18-negative patients. Collectively, our data suggest different roles for anti-HPV-18 E6 and E7 CD4(+) T cells in anti-viral and anti-tumour immunity.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Colo do Útero/virologia , Proteínas de Ligação a DNA/imunologia , Papillomavirus Humano 18/imunologia , Proteínas Oncogênicas Virais/imunologia , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Adenocarcinoma/imunologia , Adenocarcinoma/patologia , Adenocarcinoma/virologia , Adulto , Proteínas de Ligação a DNA/metabolismo , Feminino , Humanos , Ativação Linfocitária/imunologia , Pessoa de Meia-Idade , Proteínas Oncogênicas Virais/metabolismo , Infecções por Papillomavirus/imunologia , Infecções por Papillomavirus/virologia , Infecções Tumorais por Vírus/imunologia , Infecções Tumorais por Vírus/virologia , Neoplasias do Colo do Útero/imunologia , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia , Adulto Jovem , Displasia do Colo do Útero/imunologia , Displasia do Colo do Útero/patologia , Displasia do Colo do Útero/virologia
2.
Gynecol Endocrinol ; 25(8): 508-13, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19551544

RESUMO

BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common endocrine cause of hirsutism, acne and pattern alopecia, often characterised by ovulation disorders (usually manifested as oligo- or amenorrhea). In addition, 30-40% of women with PCOS have impaired glucose tolerance, and a defect in the insulin signalling pathway seems to be implicated in the pathogenesis of insulin resistance. For this reason, insulin-lowering medications represent novel approach in women with PCOS. The aim of this study was to evaluate the effects of myo-inositol (MYO), an isoform of inositol, belonging to the vitamin B complex, in the treatment of cutaneous disorders like hirsutism and acne. METHODS: Fifty patients with PCOS were enrolled in the study. BMI, LH, FSH, insulin, HOMA index, androstenedione, testosterone, free testosterone, hirsutism and acne were evaluated at the baseline and after receiving MYO therapy for 6 months. RESULTS: After 3 months of MYO administration, plasma LH, testosterone, free testosterone, insulin and HOMA index resulted significantly reduced; no significant changes were observed in plasma FSH and androstenedione levels. Both hirsutism and acne decreased after 6 months of therapy. DISCUSSION: MYO administration is a simple and safe treatment that ameliorates the metabolic profile of patients with PCOS, reducing hirsutism and acne.


Assuntos
Acne Vulgar/tratamento farmacológico , Acne Vulgar/etiologia , Hirsutismo/etiologia , Inositol/administração & dosagem , Síndrome do Ovário Policístico/complicações , Complexo Vitamínico B/administração & dosagem , Adulto , Esquema de Medicação , Feminino , Hirsutismo/tratamento farmacológico , Homeostase , Humanos , Insulina/sangue , Hormônio Luteinizante/sangue , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/tratamento farmacológico , Testosterona/sangue , Resultado do Tratamento , Adulto Jovem
3.
J Immunol ; 179(10): 7176-83, 2007 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-17982110

RESUMO

Cervical neoplastic lesions are associated with infection by high-risk human papilloma viruses (HPVs). HPV-16 and HPV-18 are the most common genotypes. It has been proposed that development of HPV-16-positive cervical lesions is associated with impaired CD4(+) T cell immunity against early Ags. The aim of the study was to evaluate whether this impairment also applies to HPV-18. We investigated the presence and the quality of anti-HPV-18 E6 CD4(+) T cell responses in the blood of 37 consecutive patients with high-grade cervical lesions, 25 normal donors, and 20 cord bloods. The immune infiltrate in the cervical lesions was also evaluated. The characteristics of the responses were correlated to the clinical outcome. We found that one or more HPV-18 E6 peptides, containing naturally processed epitopes, were able to induce a response in 40-50% of the patients, depending on the effector function tested. Importantly, these percentages rose to 80-100% when HPV-18-positive patients were considered. HPV-18 E6-specific CD4(+) T cells produced mixed Th1/Th2 responses and statistical analysis of the cytokines produced revealed that the amount of IFN-gamma released could predict infection persistence and/or disease relapse after surgery. Finally, we found that a higher number of infiltrating CD4(+) and T-bet(+) T cells in the lesions correlated with a favorable clinical outcome. Our results strongly suggest a relevant role for CD4(+) T cells in the control of the HPV-18 compared with HPV-16 infections in patients with high-grade cervical lesions and identify an immunologic parameter potentially useful for patients' stratification.


Assuntos
Proteínas de Ligação a DNA/imunologia , Papillomavirus Humano 18/imunologia , Interferon gama/imunologia , Proteínas Oncogênicas Virais/imunologia , Infecções por Papillomavirus/imunologia , Peptídeos/imunologia , Células Th1/imunologia , Células Th2/imunologia , Neoplasias do Colo do Útero/imunologia , Adulto , Apresentação de Antígeno/imunologia , Feminino , Papillomavirus Humano 16/imunologia , Humanos , Pessoa de Meia-Idade , Infecções por Papillomavirus/cirurgia , Recidiva , Resultado do Tratamento , Neoplasias do Colo do Útero/cirurgia
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