RESUMO
Kidney transplantation (KT) is the preferred treatment for end-stage renal diseases. Human leukocyte antigen G (HLA-G) and programmed death-ligand 1 (PD-L1) have notable clinical and therapeutic significance in transplantation because of their roles in promoting tolerance. This study aimed to assess HLA-G and PD-L1 levels at various stages following KT. A cohort of 12 patients was monitored from the pretransplant phase to 12 months post-surgery. Blood samples were taken at specific intervals: before kidney transplantation (T0), and then on the 7th (T7), 30th (T30), 90th (T90), 180th (T180), and 365th days post transplantation. Renal biopsies were performed in patients with graft dysfunction. Plasma levels of soluble HLA-G (sHLA-G) and PD-L1 were quantified using enzyme-linked immunosorbent assays. Additionally, immunohistochemistry was used to detect the presence of both molecules in biopsy samples. Multivariate analysis indicated that episodes of rejection were correlated with decreased expression of sHLA-G (Pâ <â .001) and PD-L1 (Pâ <â .001). Over the course of the study, the sHLA-G levels also declined (Pâ <â .001). Patients who had been transfused had lower PD-L1 levels (Pâ =â .03). Furthermore, kidney recipients from related live donors had increased HLA-G expression (Pâ <â .001). Our findings suggest that diminished HLA-G and PD-L1 levels correlate with an increased risk of graft rejection. Notably, HLA-G expression significantly decrease after the third-month posttransplantation.
Assuntos
Transplante de Rim , Humanos , Transplante de Rim/efeitos adversos , Antígenos HLA-G , Antígeno B7-H1 , Estudos de Coortes , Rejeição de EnxertoRESUMO
BACKGROUND: miR-21, miR-214 and miR-let-7a are three validated and well-known miRNAs. miR-21 is described as an "oncomir" while miR-214 and miR-let-7a are described mainly as tumor suppressors. The role of these miRNAs remains unclear in cervical cancer, an important malignancy among women worldwide and responsible for many deaths every year. OBJECTIVE: The objective of this study is to describe the expression profile of miR-21, miR-214 and miR-let-7a in plasma and in cervical scraping from a control group and patients with different grades of cervical lesions and invasive cervical cancer and correlate with HPV infection groups. METHODS: Plasma and cervical scraping were submitted to DNA and RNA extraction. HPV detection and typing were performed by conventional PCR followed by PAGE to amplicons interpretation. The miRNA relative expression in plasma and cervical scraping samples was performed by real time PCR using specific TaqMan probes. RESULTS: miR-21 (p=0.0277) and miR-214 (p=0.0151) were up-regulated in cervical scraping samples of invasive cervical cancer (ICC) group. However, miR-214 was also up-regulated in the LSIL group (p=0.0062). Both miRNAs were not related to HPV infection. However, miR-let-7a was higher in HPV positive plasma samples (p=0.0433) than in HPV negative plasma samples and the correlation analysis confirmed the association between the levels of this miRNA with the presence of HPV (p=0.0407; r=0.3029), but not with lesion grade (p>0.05). CONCLUSION: Our results suggest that miR-21 is related to cervical cancer progression and miR-214 appears to have an ambiguous role in cervical lesions. miR-let-7a may be upregulated at a systemic level in patients with HPV infection.
Assuntos
MicroRNAs , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Feminino , Humanos , MicroRNAs/genética , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/genética , Neoplasias do Colo do Útero/genéticaRESUMO
Aim: Human Leukocyte Antigen-G (HLA-G) is a non-classical class I molecule that is involved in maternal-fetal immunotolerance. In cancer, this molecule contributes to the tumor escape. The aim of this study was to evaluate the 14 bp In/Del and +3142 C > G polymorphisms of the HLA-G 3' UTR and its relation with plasma and tissue HLA-G expression in patients with grade IV (high-grade) and grade I/II (low-grade) gliomas and controls.Patients and methods: Peripheral blood and tumor biopsies were collected from 85 patients with gliomas and blood samples from 94 controls. Polymorphisms were analyzed from blood DNA. Soluble HLA-G (sHLA-G) was measured by ELISA in plasma of the subjects and the tissue expression by immunohistochemistry on patient's tissue.Results: Higher levels of sHLA-G were observed in grade IV gliomas patients than in controls (p < 0.0001). In grade IV patients, the heterozygous 14pb In/Del, +3142 C/G genotypes and Del/C*In/G haplotype were associated with higher sHLA-G levels (p < 0.0001) when compared with controls. GBM patients were stratified into high and low sHLA-G expression and an association was found between +3142 C allele and high sHLA-G plasmatic levels (p = 0.0095). Tissue HLA-G immunolabel was higher in high-grade than low-grade gliomas (p = 0.0033).Conclusion: This was the first study evaluating HLA-G 3' UTR polymorphisms and expression in patients with gliomas. The 14 bp In/Del and +3142 C/G genotypes and haplotypes showed high influence over sHLA-G expression, suggesting a heterozygous advantage in the tumor context and may contribute to a worse prognosis in glioma patients.
Assuntos
Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Glioma/genética , Glioma/metabolismo , Antígenos HLA-G/sangue , Regiões 3' não Traduzidas , Adulto , Mapeamento Encefálico , Criança , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Leber congenital amaurosis (LCA) is a severe disease that leads to complete blindness in children, typically before the first year of life. Due to the clinical and genetic heterogeneity among LCA and other retinal diseases, providing patients with a molecular diagnosis is essential to assigning an accurate clinical diagnosis. Using our gene panel that targets 300 genes that are known to cause retinal disease, including 24 genes reported to cause LCA, we sequenced 43 unrelated probands with Brazilian ancestry. We identified 42 unique variants and were able to assign a molecular diagnosis to 30/43 (70%) Brazilian patients. Among these, 30 patients were initially diagnosed with LCA or a form of early-onset retinal dystrophy, 17 patients harbored mutations in LCA-associated genes, while 13 patients had mutations in genes that were reported to cause other diseases involving the retina.
RESUMO
Besides HPV infection, the progression to cervical cancer also depends on the host immune response. HLA-G molecules are involved in the inhibition of cell-mediated immune responses and may permit the development of an infection in the female cervical tract. The aim of this study was to explore the possible influence of the two HLA-G polymorphisms located on the 3'UTR on the susceptibility to cervical cancer and risk factors in Brazilian patients. Polymorphism analysis (14 bp In/Del and +3142C/G) was performed by PCR. A total of 105 cervical samples were tested, 50 without lesions and 55 with lesions; 22 with high grade (HSIL) and 33 with invasive cancer (ICC). The polymorphisms (∗)Del/Del was associated with a decreased risk of developing ICC in smokers and (∗)In and (∗)In/In were associated with an increased risk of HSIL and a higher risk of ICC in smokers. The genotype (∗)In/Del was associated with the increased risk of HSIL only among women with a family history of cancer. The haplotypes (∗)In/G and (∗)Del/G were associated with increased and decreased risk of HSIL and cervical cancer, respectively. In conclusion, the 3'UTR of HLA-G is associated with an increased risk of developing cervical cancer, especially in smokers.
Assuntos
Regiões 3' não Traduzidas , Antígenos HLA-G/genética , Polimorfismo Genético , Displasia do Colo do Útero/genética , Neoplasias do Colo do Útero/genética , Neoplasias Vaginais/genética , Adulto , Idoso , Análise Mutacional de DNA , Feminino , Haplótipos , Hereditariedade , Humanos , Pessoa de Meia-Idade , Mutação , Gradação de Tumores , Fatores de Risco , Fumar , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/patologia , Neoplasias Vaginais/diagnóstico , Neoplasias Vaginais/patologia , Displasia do Colo do Útero/diagnóstico , Displasia do Colo do Útero/patologiaRESUMO
Laryngeal squamous cell carcinoma is one of the most common malignant neoplasms of the head and neck. In Brazil, laryngeal tumors represent 2% of all cancers and are associated with approximately 3,000 deaths annually. Human papillomavirus (HPV) has been reported to play an important role in the etiology of laryngeal cancer. The aim of the present study was to evaluate the expression of p53, p27, and Mdm2 in laryngeal carcinomas. Sixty-three larynx biopsies were selected for the study, including 9 in situ laryngeal carcinomas, 27 laryngeal carcinomas without metastasis and 27 laryngeal carcinomas with metastasis. Twenty-seven cervical lymph nodes from patients with metastatic lesions were also evaluated. The expression levels of p53, p27, and Mdm2 were assessed by immunohistochemistry using a computer-assisted system. HPV detection and typing were performed using PCR, and the HPV types that were evaluated included HPV 6, 11, 16, 18, 31 and 33. Out of 63 patients, 53 (84.1%) were positive for ß-globin (internal control), and 10 (15.9%) were ß-globin negative and therefore excluded from the evaluation. Thus, 7 (13.2%) out of 53 patients were HPV positive, and 46 (86.8%) out of 53 patients were HPV negative. Statistically significant differences (p < 0.05) in Mdm2 expression levels were observed in the in situ laryngeal carcinoma samples compared with the laryngeal carcinoma samples with metastasis. No statistically significant differences (p > 0.05) in either p53 or p27 expression levels were detected. These findings suggest that Mdm2 may be associated with the invasiveness and aggressiveness of laryngeal carcinomas.
Assuntos
Carcinoma de Células Escamosas , Neoplasias Laríngeas , Laringe/patologia , Proteínas Proto-Oncogênicas c-mdm2/genética , Biomarcadores Tumorais , Biópsia , Brasil/epidemiologia , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/etiologia , Carcinoma de Células Escamosas/patologia , Feminino , Expressão Gênica , Humanos , Neoplasias Laríngeas/epidemiologia , Neoplasias Laríngeas/etiologia , Neoplasias Laríngeas/patologia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Metástase Neoplásica/genética , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/virologia , Fatores de RiscoRESUMO
INTRODUCTION: Human leukocyte antigen (HLA)-G is a nonclassic class I molecule that acts as a modulator of immune responses, and the expression of these molecules in virus-infected cells has been associated with subversion of the immune response. OBJECTIVE: In this study, we performed a cross-sectional study, systematically comparing the expression of the HLA-G in benign, premalignant, and malignant oral lesions and correlating it with the presence of high-risk and low-risk human papillomavirus (HPV) types. SPECIMENS AND METHODS: Oral biopsies were collected from 51 patients and analyzed by immunohistochemistry using anti-HLA-G antibody. Human papillomavirus detection and typing from oral biopsies were obtained by polymerase chain reaction using GP5+/GP6+ and specific primers. RESULTS: The 51 biopsies were stratified into 3 groups according to lesion grade: oral benign lesions (oral hyperplasia and papilloma, n = 16), oral premalignant lesions (oral leukoplakia with dysplasia and lichen planus, n = 17), and malignant lesions (oral squamous cell carcinoma, n = 18). Human leukocyte antigen-G overexpression was mainly observed in benign and premalignant oral lesions but was not related to HPV infection (P > .05). On the other hand, HPV DNA was detected in 24 (47%) oral lesions, mainly in benign and premalignant lesions, with the most frequent type detected being high-risk HPV type. CONCLUSION: The HLA-G molecule was expressed in a significant number of benign oral lesions and was not correlated with HPV infection or oral cancer.
Assuntos
Antígenos HLA-G/biossíntese , Imunidade Celular , Neoplasias Bucais/metabolismo , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/imunologia , Biópsia , Estudos Transversais , Seguimentos , Antígenos HLA-G/imunologia , Humanos , Imuno-Histoquímica , Mucosa Bucal/metabolismo , Mucosa Bucal/patologia , Neoplasias Bucais/imunologia , Neoplasias Bucais/patologia , Estudos RetrospectivosRESUMO
INTRODUCTION: HLA-G and HLA-E are two nonclassical class I molecules, which have been well recognized as modulators of innate and adaptive immune responses, and the expression of these molecules in virus infected cells has been associated with subversion of the immune response. OBJECTIVE: In this study we performed a cross-sectional study, systematically comparing the expression of HLA-G and HLA-E in benign, pre-malignant and malignant laryngeal lesions, correlating with demographic and clinical variables and with the presence of high-risk and low-risk HPV types. MATERIALS AND METHODS: Laryngeal lesions were collected from 109 patients and stratified into 27 laryngeal papillomas, 17 dysplasias, 10 in situ laryngeal carcinomas, 27 laryngeal carcinomas without metastases, 28 laryngeal carcinomas with metastasis along with their respective draining cervical lymph nodes, and 10 normal larynx specimens. The expression of HLA-G and HLA-E molecules was determined by immunohistochemistry. HPV DNA detection and typing was performed using generic and specific primers. RESULTS: HLA nonclassical molecules showed a distinct distribution pattern, according to the larynx lesion grade. HLA-G expression increased in benign and premalignant lesions, and gradually decreased in invasive carcinomas and in respective draining cervical lymph nodes. Conversely, HLA-E expression increased as far as lesion grade increased, including increased molecule expression in the draining lymph nodes of malignant lesions. Only 17 (15.6%) patients were HPV DNA positive. CONCLUSIONS: Overexpression of HLA-E and underexpression of HLA-G appear to be good markers for malignant larynx lesion.
Assuntos
Biomarcadores Tumorais/análise , Carcinoma in Situ/imunologia , Carcinoma/imunologia , Antígenos HLA-G/análise , Antígenos de Histocompatibilidade Classe I/análise , Neoplasias Laríngeas/imunologia , Papiloma/imunologia , Lesões Pré-Cancerosas/imunologia , Adulto , Idoso , Análise de Variância , Biópsia , Brasil , Carcinoma/secundário , Carcinoma/virologia , Carcinoma in Situ/patologia , Carcinoma in Situ/virologia , Estudos Transversais , DNA Viral/análise , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Laríngeas/patologia , Neoplasias Laríngeas/virologia , Linfonodos/imunologia , Linfonodos/patologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Razão de Chances , Papiloma/patologia , Papiloma/virologia , Papillomaviridae/genética , Reação em Cadeia da Polimerase , Lesões Pré-Cancerosas/patologia , Lesões Pré-Cancerosas/virologia , Antígenos HLA-ERESUMO
Oral squamous cell carcinoma (OSCC) is the most common head and neck cancer. Only in Brazil, the estimate is for 14,160 new cases in 2009. HPV is associated with increasing risk of oral cancer, but its role in carcinogenesis is still controversial. BUBR1, an important protein in the mitotic spindle assembly checkpoint (SAC), has been associated with some virus-encoded proteins and cancer. The aim of the present study was to evaluate the expression of BUBR1 in non-malignant oral lesions and OSCC with and without metastasis associated with HPV infection. We performed immunohistochemistry for BUBR1 in 70 OSCC biopsies divided into three groups (in situ tumors, invasive tumors without metastasis and invasive tumors with metastasis) with their respective lymph nodes from samples with metastasis and in 16 non-malignant oral lesions. PCR was performed in order to detect HPV DNA. Significantly higher BUBR1 expression associated with shorter survival (p=0.0479) was observed in malignant lesions. There was also a significant correlation (r=1.000) with BUBR1 expression in lesions with metastasis and their lymph nodes. Ninety percent of OSCC and 100% of benign lesions were HPV positive. HPV16 and HVP18 were present in 13 and 24% of HPV-positive OSCC samples, respectively. HPV was more prevalent (76%) in samples with a high BUBR1 expression and the absence of viral DNA had no influence on BUBR1 expression. These findings suggest that HPV could be associated with overexpression of BUBR1 in OSCC, but not in benign oral lesions.
Assuntos
Carcinoma in Situ/genética , Carcinoma de Células Escamosas/genética , Neoplasias Bucais/genética , Infecções por Papillomavirus/epidemiologia , Proteínas Serina-Treonina Quinases/biossíntese , Carcinoma in Situ/patologia , Carcinoma in Situ/virologia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/virologia , Feminino , Expressão Gênica , Perfilação da Expressão Gênica , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/patologia , Neoplasias Bucais/virologia , Infecções por Papillomavirus/complicações , Prevalência , Proteínas Serina-Treonina Quinases/genética , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Human leukocyte antigen-G (HLA-G) is a non-classical major histocompatibility complex class Ib molecule that acts as a specific immunosuppressor. Some studies have demonstrated that human papillomavirus (HPV) seems to be involved in lower or absent HLA-G expression, particularly in cervical cancer. In this study, we performed a cross-sectional study, systematically comparing the qualitative expression of the HLA-G5 isoform in invasive cervical carcinoma (ICC), stratifying patients according to the presence [ICC with metastasis (ICC(W))] and absence [ICC without metastasis (ICC(WT))] of metastasis, correlating these findings with interference of HPV and demographic and clinical variables. Seventy-nine patients with a diagnosis of ICC were stratified into two groups: ICC(WT) (n=52 patients) and ICC(W) (n=27). Two biopsies were collected from each patient (one from the tumor lesion and one from a lymph node). Immunohistochemistry analyses were performed for the HLA-G5 isoform, for HPV detection, and virus typing. HLA-G5 isoform molecules were detected in 25 cases (31.6%), 17 (32.7%) without metastasis and 8 (29.6%) with metastasis. HPV was detected in the cervical lesions of 74 patients (93.7%), but low expression of the HLA-G5 isoform was observed in all HPV-related cases. These findings are important; however, additional studies are necessary to identify the influence of HPV with HLA-G5 isoform expression on invasive cervical malignancies.