Characterization of Immunoglobulin A/G Responses During 3 Doses of the Human Papillomavirus-16/18 ASO4-Adjuvanted Vaccine.

BACKGROUND: Individuals receiving the human papillomavirus (HPV) vaccine develop high levels of circulating neutralizing antibodies. However, data about antibody responses in the cervix are limited. METHODS: This study was designed to describe the course of IgA/IgG responses in cervical secretions and in serum after intramuscular administration of the HPV16/18 AS04-adjuvant vaccine. An enzyme-linked immunosorbent assay for detection of IgA and IgG anti-HPV-VLP was developed for this purpose. RESULTS: Immunoglobulin G seroconversion after the second dose was observed in 100% of the participants and remained 1 month after the third dose. Regarding IgG reactivity in cervical secretions, conversion was observed in 85% of women after the final dose. Immunoglobulin A seroconversion was observed in 76.7% of women after the third dose. Lower levels of IgA were detected in the cervical mucus (28.3%) and decreased to 23.3% after the last dose. Comparing local and systemic IgG responses, positivity in both serum and cervical samples was observed in 85%, whereas in 15% only, the serum was IgG antibody positive. A weak agreement between local and systemic IgA responses was observed. Only 18.3% of participants were local and systemic IgA positive, 58.4% were positive only in serum, 5% were positive only in the cervix, and 18.3% were both local and systemic IgA antibody negative. CONCLUSIONS: After the third vaccination, there is a strong agreement between cervical and systemic IgG antibody responses and a weak agreement between cervical and systemic IgA antibody responses. The induction of IgA antibodies seems to be secondary to that of IgG antibodies in response to HPV intramuscular vaccination.

Genetic polymorphisms of Interleukin-18 are not associated with allograft function in kidney transplant recipients.

Interleukin 18 (IL-18) is a proinflammatory cytokine that plays a role in host defense by upregulating both innate and acquired immune responses. Analysis of IL18 polymorphisms may be clinically important since their roles have been recognized in a variety of inflammatory and autoimmune disorders. However, the role of this cytokine polymorphisms in kidney transplant still remains unclear. In this study, we evaluated the associations between IL18 polymorphisms and graft function assessed by creatinine clearance in kidney transplant recipients. A total of 82 kidney transplant recipients and 183 healthy controls were enrolled, and frequencies of alleles, genotypes and haplotypes for IL18 polymorphisms were determined and compared with creatinine clearance. The -607C/A (rs1946518) and -137C/G (rs187238) variant alleles in the IL18 gene were determined by polymerase chain reaction. In our study, no significant association was found between the IL18 variants and creatinine clearance (p > 0.05). Nonetheless, polymorphism analysis revealed an increase in the frequency of the IL18 major haplotype -607C/-137G in kidney transplant patients (odds ratio 2.57, 95% confidence interval 1.45-4.55, p = 0.0014). Finally, we found that IL18 polymorphisms did not influence the renal function and that IL18 haplotype -607C/-137G seems to be associated with kidney transplant recipients.

Evaluation of Exosomal miRNA as Potential Biomarkers in Cervical Cancer.

Different studies show that small non-coding RNAs, such as microRNAs (miRNAs) obtained from exosomes, are considered potential biomarkers in several types of cancer, including cervical cancer (CC). Therefore, the present study seeks to present an overview of the role of circulating exosomal miRNAs with the potential to act as biomarkers for the diagnosis and prognosis of CC and to analyze the presence of these miRNAs according to the stage of CC. For this purpose, a review was developed, with articles consulted from the electronic databases MEDLINE/PubMed, Scopus, and Web of Science published between 2015 and 2021. Seven articles were included after a selection of studies according to the eligibility criteria. In addition to the methods used for sample analysis, detection, and isolation of miRNAs in each article, clinical data were also extracted from the patients studied, such as the stage of cancer. After analyzing the network of the seven miRNAs, they were associated with the immune system, CC progression and staging, and cisplatin resistance. With the belief that studies on miRNAs in cervical cancer would have major clinical implications, in this review, we have attempted to summarize the current situation and potential development prospects.

Microablative fractional radiofrequency for sexual dysfunction and vaginal Trophism: A randomized clinical trial.

OBJECTIVES: To evaluate Microablative Fractional Radiofrequency (MAFRF) as a possible option in treating vaginal atrophy. METHODS: This was a randomized, controlled clinical trial with postmenopausal women diagnosed with vaginal atrophy. The treatment consisted of three sessions of MAFRF, compared to vaginal estrogen administration and an untreated control group. Assessments occurred at baseline and 90 days. The primary endpoints were sexual function, evaluated by the Female Sexual Function Index (FSFI), and vaginal health, assessed by the Vaginal Health Index (VHI). Secondary outcomes included vaginal microbiota composition (Nugent score) and epithelial cell maturation (Maturation Value ‒ MV). RESULTS: One hundred and twenty women (40 in each group) were included. Concerning the FSFI, both groups, MAFRF (median 4.8 [3.6‒6.0]) and vaginal estrogen (mean 4.7 ± 1.1), experienced improved sexual desire when compared to the control group (median 3.6 [2.4‒4.8]). Regarding the total score of VHI, the authors observed an improvement in the mean of the MAFRF (23.7 ± 2.0) and vaginal estrogen groups (23.5 ± 1.9) when compared to the control (14.8 ± 2.9). The Nugent score was reduced in the MAFRF and estrogen groups (p < 0.01) compared to the control group. Lastly, the MV was modified after treatment with MAFRF (p < 0.01) and vaginal estrogen (p < 0.001). No differences existed between the MAFRF and vaginal estrogen groups in the studied variables. No adverse effects were reported following the MAFRF protocol. CONCLUSIONS: Radiofrequency was comparable in efficacy to estrogen administration for treating vulvovaginal atrophy. It deserves consideration as a viable option in managing this condition.

Spectrochemical differentiation in gestational diabetes mellitus based on attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy and multivariate analysis.

Gestational diabetes mellitus (GDM) is a hyperglycaemic imbalance first recognized during pregnancy, and affects up to 22% of pregnancies worldwide, bringing negative maternal-fetal consequences in the short- and long-term. In order to better characterize GDM in pregnant women, 100 blood plasma samples (50 GDM and 50 healthy pregnant control group) were submitted Attenuated Total Reflection Fourier-transform infrared (ATR-FTIR) spectroscopy, using chemometric approaches, including feature selection algorithms associated with discriminant analysis, such as Linear Discriminant Analysis (LDA), Quadratic Discriminant Analysis (QDA) and Support Vector Machines (SVM), analyzed in the biofingerprint region between 1800 and 900 cm-1 followed by Savitzky-Golay smoothing, baseline correction and normalization to Amide-I band (~ 1650 cm-1). An initial exploratory analysis of the data by Principal Component Analysis (PCA) showed a separation tendency between the two groups, which were then classified by supervised algorithms. Overall, the results obtained by Genetic Algorithm Linear Discriminant Analysis (GA-LDA) were the most satisfactory, with an accuracy, sensitivity and specificity of 100%. The spectral features responsible for group differentiation were attributed mainly to the lipid/protein regions (1462-1747 cm-1). These findings demonstrate, for the first time, the potential of ATR-FTIR spectroscopy combined with multivariate analysis as a screening tool for fast and low-cost GDM detection.

Immunohistochemical evaluation of HLA-G and FoxP3+ T regulatory cells in oral cavity and lower lip squamous cell carcinomas.

Human Leukocyte Antigen G (HLA-G) is a molecule involved in the tumor immunosuppression and also in the generation of regulatory T (Treg) cells, thus leading to evasion to the immune system host, and consequently, contributing to tumor progression in several cancers. The aim of this study was to evaluate the immunoexpression of HLA-G by tumor cells and FoxP3+ Treg cells in 25 oral tongue squamous cell carcinomas (SCCs) and 25 lower lip SCCs and analyze their relationship with clinical parameters. HLA-G expression was higher in oral tongue SCCs than in lower lip SCCs. In oral tongue SCCs and lower lip SCCs, no association between HLA-G expression and clinical parameters (tumor size, lymph node status, distant metastasis, and clinical stage) was verified (P>0.05). FoxP3+ Treg cells were detected along the tumor invasive front in all cases of oral tongue and lower lip SCCs. In oral tongue SCC cases, the number of Treg cells tended to be higher in smaller tumors, tumors without regional lymph node metastasis, and tumors in early clinical stages, but the difference was not statistically significant (P>0.05). A significant positive correlation was found between the expression of HLA-G by neoplastic cells and Treg cells in lower lip SCCs (p = 0.008). Our findings suggest the involvement of HLA-G and Treg cells in the modulation of immune responses in oral tongue and lower lip SCCs. This interaction between HLA-G and Treg cells may represent an evasion mechanism in these malignancies.

Tityus serrulatus Scorpion Venom Induces Apoptosis in Cervical Cancer Cell Lines.

Cervical cancer (CC) is classified as the fourth most common type of cancer in women worldwide and remains a serious public health problem in many underdeveloped countries. Human papillomavirus (HPV), mainly types 16 and 18, has been established as a precursory etiologic agent for this type of cancer. Several therapeutic attempts have been studied and applied, aiming at its control. However, not only do classical treatments such as chemotherapies and radiotherapies target tumor cells, but also they cause damage to several healthy cells. For these reasons, the search for new biologically active chemotherapeutic components is of great importance. In this study, we investigated the effect of Tityus serrulatus scorpion venom (TsV) on CC lines. There are very few studies exploring venom of scorpions, and, to our knowledge, no study has been conducted using the venom of the scorpion TsV for treatment of cervical cancer lines. After challenge with TsV, the MTT assay demonstrated cytotoxic effect on HeLa line. Similarly, the cell death process in HeLa analyzed by flow cytometry suggests death via caspase, since the pan-caspase inhibitor z-VAD-fmk significantly reduced the apoptotic response to the treatment. These results suggest that venom of TsV can be a potential source for the isolation of effective antiproliferative and apoptotic molecules in the treatment of CC.

Does 100% Rapid Review Improve Cervical Cancer Screening?

OBJECTIVE: The aim of this work was to evaluate 100% rapid review (100% RR) as a useful tool to detect false negative (FN) results. STUDY DESIGN: A sample of 8,677 swabs was investigated; the unsatisfactory and negative results were referred to 100% RR, concordant results were taken as the final diagnosis, while the discordant results were debated in a consensus meeting to reach a conclusion. The positive results were examined by 2 cytologists. The data were entered into SAS statistical software, and the agreement of the 100% RR results with the final diagnosis was tested with the weighted kappa statistic. RESULTS: There was a significant increase in unsatisfactory results from 348 to 1,927, and of positive results from 174 to 349. On the other hand, there was a substantial decrease in negative results from 8,155 to 6,401. Assessing the relative risk of FN results in smears that were not referred to quality control (100% RR) revealed the following results: atypical squamous cells of undetermined significance (ASC-US), 2.93; low-grade squamous intraepithelial lesion (LSIL), 2.72; high-grade squamous intraepithelial lesion/atypical squamous cells - cannot exclude HSIL (HSIL/ASC-H), 2.25. Evaluating by age group, a higher risk for LSIL (4.90) and ASC-US (3.85) was observed in patients aged under 25 years, whereas patients between 25 and 64 years and those over 64 years presented a higher risk for HSIL and ASC-H: 2.46 and 2.75, respectively. CONCLUSION: 100% RR is an effective screening tool for FN results in countries where molecular tests for DNA-HPV and prophylactic vaccines are not available in cervical cancer screening programs.

Microablative fractional radiofrequency for sexual dysfunction and vaginal Trophism: A randomized clinical trial

Abstract Objectives: To evaluate Microablative Fractional Radiofrequency (MAFRF) as a possible option in treating vaginal atrophy. Methods: This was a randomized, controlled clinical trial with postmenopausal women diagnosed with vaginal atrophy. The treatment consisted of three sessions of MAFRF, compared to vaginal estrogen administration and an untreated control group. Assessments occurred at baseline and 90 days. The primary endpoints were sexual function, evaluated by the Female Sexual Function Index (FSFI), and vaginal health, assessed by the Vaginal Health Index (VHI). Secondary outcomes included vaginal microbiota composition (Nugent score) and epithelial cell maturation (Maturation Value ‒ MV). Results: One hundred and twenty women (40 in each group) were included. Concerning the FSFI, both groups, MAFRF (median 4.8 [3.6‒6.0]) and vaginal estrogen (mean 4.7 ± 1.1), experienced improved sexual desire when compared to the control group (median 3.6 [2.4‒4.8]). Regarding the total score of VHI, the authors observed an improvement in the mean of the MAFRF (23.7 ± 2.0) and vaginal estrogen groups (23.5 ± 1.9) when compared to the control (14.8 ± 2.9). The Nugent score was reduced in the MAFRF and estrogen groups (p < 0.01) compared to the control group. Lastly, the MV was modified after treatment with MAFRF (p < 0.01) and vaginal estrogen (p < 0.001). No differences existed between the MAFRF and vaginal estrogen groups in the studied variables. No adverse effects were reported following the MAFRF protocol. Conclusions: Radiofrequency was comparable in efficacy to estrogen administration for treating vulvovaginal atrophy. It deserves consideration as a viable option in managing this condition.

High IL-17 expression is associated with an unfavorable prognosis in thyroid cancer.

Previous studies have indicated that cancer may be promoted and/or exacerbated by inflammation and infection. The cytokines produced by activated innate immune cells that stimulate tumor growth and progression are considered as important components in this process. The interleukin (IL)-23/T helper (Th)17 axis, which exerts marked pro-inflammatory effects, has emerged as an important mediator in inflammation-associated cancer. Increasing clinical evidence indicates that Th17 may promote or inhibit tumor progression, however, the function of Th17 in the pathogenesis of benign and malignant thyroid neoplasms remains unclear. The present study investigated the association between the IL-23/Th17 axis and neoplastic and non-neoplastic thyroid lesions using immunohistochemistry. A total of 131 thyroid biopsy specimens were analyzed, which revealed high IL-17 and IL-23 expression in differentiated thyroid cancer and medullary thyroid cancer tissues when compared with benign lesions, including follicular thyroid adenoma and goiter tissues. Furthermore, high IL-17 expression was associated with recurrence and mortality. These results indicate that the IL-23/Th17 axis exhibits a pivotal function in the development of thyroid neoplasms.

Histomorphometric analysis in HPV-induced cervical lesions

SUMMARY Introduction: squamous intraepithelial lesions (SIL) of the cervix involve dysplastic change, or abnormal cell maturation and their progression can result in cervical carcinoma. Some studies have reported the importance of the immune system in the process of tumor progression. Therefore, it is important to characterize the inflammatory infiltration as a possible marker of prognosis. Aim: to analyze density of the inflammatory infiltrate in different degrees of SIL and in cervical cancer to under-stand local and systemic changes in the interactions between HPV associated cervical lesions and the immune system. Methods: one hundred and eight (108) cervical biopsy specimens were obtained from patients treated at the tertiary hospital and were stratified into four groups: Low-grade squamous intraepithelial lesion (LSIL), High-grade squamous intraepithelial lesion (HSIL), cervical cancer (CC) and negative for intraepithelial lesion and malignancy (NILM). Histomorphometric analysis was performed from the identification and quantification of inflammatory cells in ten (10) fields per sample in images captured by a digital system and analyzed using the software Leica Qwin Pro V 3.5.1, Leica Microsystems Ltd. Differences between groups were evaluated by Anova followed by Tukey test. Tests yielding p values < 0.05 were considered significant. Results: we found a significant increase in the average number of lymphocytes (cells/mm2 and cells/field) in samples of CC in relation to the other groups. No statistical difference was observed in relation to neutrophils, plasma cells and eosinophils. Conclusion: cervical cancer specimens had significantly more lymphocytes than NILM, or LSIL and HSIL, suggesting that this cell type plays a central role in cellular immunity against cervical carcinoma.

Introducción: las lesiones escamosas intraepiteliales (SIL) del cuello uterino implican cambios displásicos o maduración celular anormal y su progresión puede resultar en carcinoma cervical. Algunos estudios han informado de la importancia del sistema inmunológico en el proceso de progresión tumoral. Por tanto, es importante caracterizar la infiltración inflamatoria como un posible marcador de pronóstico. Objetivo: analizar la densidad del infiltrado inflamatorio en diferentes grados de SIL y en cáncer de cuello uterino para comprender los cambios locales y sistêmicos en las interacciones entre las lesiones cervicales asociadas al VPH y el sistema inmunológico. Métodos: se obtuvieron ciento ocho (108) muestras de biopsia cervical de pacientes tratados en el hospital terciario y se estratificaron en cuatro grupos: Lesión intraepitelial escamosa de bajo grado (LSIL), Lesión intraepitelial escamosa de alto grado (HSIL), cáncer de cuello uterino (CC) y negativo para lesiones intraepiteliales y malignidad (NILM). El análisis histomorfométrico se realizó a partir de la identificación y cuantificación de células inflamatorias en diez (10) campos por muestra en imágenes capturadas por un sistema digital y analizadas utilizando el software Leica Qwin Pro-V 3.5.1, Leica Microsystems Ltd. Anova seguido de la prueba de Tukey. Las pruebas que arrojaron valores de p <0,05 se consideraron significativas. Resultados: encontramos un aumento significativo en el número medio de linfocitos (células/mm2 y células/campo) en muestras de CC en relación con los otros grupos. No se observó diferencia estadística en relación con neutrófilos, células plasmáticas y eosinófilos. Conclusión: las muestras de cáncer de cuello uterino tenían significativamente más linfocitos que NILM o LSIL y HSIL, lo que sugiere que este tipo de células juega un papel central en la inmunidad celular contra el carcinoma de cuello uterino.

Introdução: Lesões intraepiteliais escamosas (SIL) do colo do útero envolvem alteração displásica ou maturação celular anormal e sua progressão pode resultar em carcinoma cervical. Alguns estudos relatam a importância do sistema imunológico no processo de progressão tumoral. Portanto, é importante caracterizar o infiltrado inflamatório como um possível marcador de prognóstico. Objetivo: analisar a densidade do infiltrado inflamatório em diferentes graus de SIL e no câncer cervical para compreender as alterações locais e sistêmicas nas interações entre as lesões cervicais associadas ao HPV e o sistema imunológico. Métodos: Cento e oito (108) espécimes de biópsia cervical foram obtidos de pacientes tratados no hospital terciário e foram estratificados em quatro grupos: Lesão intraepitelial escamosa de baixo grau (LSIL), Lesão intraepitelial escamosa de alto grau (HSIL), câncer cervical (CC) e negativo para lesão intraepitelial e malignidade (NILM). A análise histomorfométrica foi realizada a partir da identificação e quantificação das células inflamatórias em dez (10) campos por amostra em imagens capturadas por um sistema digital e analisadas no software Leica Qwin Pro V 3.5.1, Leica Microsystems Ltd. As diferenças entre os grupos foram avaliadas por Anova seguida do teste de Tukey. Os testes com valores de p <0,05 foram considerados significativos. Resultados: encontramos um aumento significativo no número médio de linfócitos (células/mm2 e células/campo) nas amostras de CC em relação aos demais grupos. Não foi observada diferença estatística em relação aos neutrófilos, plasmócitos e eosinófilos. Conclusão: as amostras de câncer cervical tinham significativamente mais linfócitos do que NILM, ou LSIL e HSIL, sugerindo que este tipo de célula desempenha um papel central na imunidade celular contra o carcinoma cervical.

Bothrops jararaca and Bothrops erythromelas Snake Venoms Promote Cell Cycle Arrest and Induce Apoptosis via the Mitochondrial Depolarization of Cervical Cancer Cells.

Bothrops jararaca (BJ) and Bothrops erythromelas (BE) are viper snakes found in South-Southeast and Northeast regions of Brazil, respectively. Snake venoms are bioactive neurotoxic substances synthesized and stored by venom glands, with different physiological and pharmacological effects, recently suggesting a possible preference for targets in cancer cells; however, mechanisms of snakes have been little studied. Here, we investigated the mechanism responsible for snake crude venoms toxicity in cultured cervical cancer cells SiHa and HeLa. We show that BJ and BE snake crude venoms exert cytotoxic effects to these cells. The percentage of apoptotic cells and cell cycle analysis and cell proliferation were assessed by flow cytometry and MTT assay. Detection of mitochondrial membrane potential (Rhodamine-123), nuclei morphological change, and DNA fragmentation were examined by staining with DAPI. The results showed that both the BJ and BE venoms were capable of inhibiting tumor cell proliferation, promoting cytotoxicity and death by apoptosis of target SiHa and HeLa cells when treated with BJ and BE venoms. Furthermore, data revealed that both BJ venoms in SiHa cell promoted nuclear condensation, fragmentation, and formation of apoptotic bodies by DAPI assay, mitochondrial damage by Rhodamine-123, and cell cycle block in the G1-G0 phase. BJ and BE venoms present anticancer potential, suggesting that both Bothrops venoms could be used as prototypes for the development of new therapies.

Greater expression of the human leukocyte antigen-G (HLA-G) and interleukin-17 (IL-17) in cervical intraepithelial neoplasia: analytical cross-sectional study.

CONTEXT AND OBJECTIVE: Impaired local cell immunity seems to contribute towards the pathogenesis and progression of cervical intraepithelial neoplasia (CIN), but the underlying molecular mechanisms promoting its progression remain unclear. Identification of new molecular markers for prognosis and diagnosis of early-stage CIN may aid in decreasing the numbers of CIN cases. Several novel immunoregulatory molecules have been discovered over the past few years, including the human leukocyte antigen G (HLA-G), which through interaction with its receptors exerts important tolerogenic functions. Several lines of evidence suggest that T-helper interleukin-17 (IL-17)-producing cells (Th17 cells) may play a role in antitumor immunity. However, recent reports have implicated Th17 cells and their cytokines in both pro and anti-tumorigenic processes. The aim of the study was to evaluate the roles of HLA-G and Th17 in the immunopathogenesis of CIN I. DESIGN AND SETTING: Analytical cross-sectional study with a control group using 58 cervical specimens from the files of a public university hospital providing tertiary-level care. METHODS: We examined HLA-G and IL-17 expression in the cervical microenvironment by means of immunohistochemistry, and correlated these findings with clinical and pathological features. RESULTS: There was a greater tendency towards HLA-G and IL-17 expression in specimens that showed CIN I, thus suggesting that these molecules have a contribution towards cervical progression. CONCLUSION: These findings suggest that HLA-G and IL-17 expression may be an early marker for assessing the progression of cervical lesions.

Immunohistochemical evaluation of HLA-G and FoxP3+ T regulatory cells in oral cavity and lower lip squamous cell carcinomas

Abstract: Human Leukocyte Antigen G (HLA-G) is a molecule involved in the tumor immunosuppression and also in the generation of regulatory T (Treg) cells, thus leading to evasion to the immune system host, and consequently, contributing to tumor progression in several cancers. The aim of this study was to evaluate the immunoexpression of HLA-G by tumor cells and FoxP3+ Treg cells in 25 oral tongue squamous cell carcinomas (SCCs) and 25 lower lip SCCs and analyze their relationship with clinical parameters. HLA-G expression was higher in oral tongue SCCs than in lower lip SCCs. In oral tongue SCCs and lower lip SCCs, no association between HLA-G expression and clinical parameters (tumor size, lymph node status, distant metastasis, and clinical stage) was verified (P>0.05). FoxP3+ Treg cells were detected along the tumor invasive front in all cases of oral tongue and lower lip SCCs. In oral tongue SCC cases, the number of Treg cells tended to be higher in smaller tumors, tumors without regional lymph node metastasis, and tumors in early clinical stages, but the difference was not statistically significant (P>0.05). A significant positive correlation was found between the expression of HLA-G by neoplastic cells and Treg cells in lower lip SCCs (p = 0.008). Our findings suggest the involvement of HLA-G and Treg cells in the modulation of immune responses in oral tongue and lower lip SCCs. This interaction between HLA-G and Treg cells may represent an evasion mechanism in these malignancies.

Upregulation of soluble and membrane-bound human leukocyte antigen G expression is primarily observed in the milder histopathological stages of chronic hepatitis C virus infection.

Chronic hepatitis C virus (HCV) infection is a worldwide health problem that may evolve to cirrhosis and hepatocellular carcinoma. Incompletely understood immune system mechanisms have been associated with impaired viral clearance. The nonclassical class I human leukocyte antigen G (HLA-G) molecule may downregulate immune system cell functions exhibiting well-recognized tolerogenic properties. HCV genotype was analyzed in chronic HCV-infected patients. Because HLA-G expression may be induced by certain viruses, we evaluated the presence of HLA-G in the liver microenvironment obtained from 89 biopsies of patients harboring chronic HCV infection and stratified according to clinical and histopathological features. Overall, data indicated that HCV genotype 1 was predominant, especially subgenotype 1a, with a prevalence of 87%. HLA-G expression was observed in 45 (51%) liver specimens, and it was more frequent in milder stages of chronic hepatitis (67.4%) than in moderate (27.8%; p = 0.009) and severe (36.0%; p = 0.021) stages of the disease. Altogether, these results suggest that the expression of HLA-G in the context of HCV is a complex process modulated by many factors, which may contribute to an immunologic environment favoring viral persistence. However, because the milder forms predominantly expressed HLA-G, a protective role of this molecule may not be excluded.

Human leukocyte antigen-G 3' untranslated region polymorphisms are associated with better kidney allograft acceptance.

Human leukocyte antigen-G (HLA-G) plays a well-recognized role in the modulation of the immune response, and HLA-G expression has been associated with increased graft survival and decreased rejection episodes. To investigate the role of the HLA-G 3' untranslated region (3'UTR) in renal transplantation, we evaluated several polymorphic sites (14-bp Del/Ins +3003T/C, +3010C/G, +3027C/A, +3035C/T, +3142G/C, and +3187A/G) in patients exhibiting or not exhibiting rejection episodes. A total of 104 patients (15 with acute and 48 with chronic rejection, and 41 with no rejection) and 142 healthy individuals were studied. HLA-G 3'UTR was typed by direct sequencing. The +3035C-C genotype was more frequent in patients exhibiting chronic rejection compared with healthy controls, and the +3035C-T genotype was less frequent in chronic rejection compared with patients without rejection (acute plus chronic) or compared with healthy controls. The +3187G-A genotype, in which the A allele is associated with increased mRNA degradation, showed increased frequency in the rejection group (acute plus chronic) when compared with healthy controls. The 14 base pair Deletion/Insertion genotype was marginally increased in patients with acute rejection. This is the first study to show associations among numerous polymorphic sites in the HLA-G 3'UTR in kidney allotransplantation, which may contribute to the understanding of HLA-G post-transcriptional mechanisms.

Greater expression of the human leukocyte antigen-G (HLA-G) and interleukin-17 (IL-17) in cervical intraepithelial neoplasia: analytical cross-sectional study / Aumento da expressão do antígeno leucocitário humano-G (HLA-G) e interleucina-17 (IL-17) em neoplasia intraepitelial cervical: estudo transversal analítico

CONTEXT AND OBJECTIVE:Impaired local cell immunity seems to contribute towards the pathogenesis and progression of cervical intraepithelial neoplasia (CIN), but the underlying molecular mechanisms promoting its progression remain unclear. Identification of new molecular markers for prognosis and diagnosis of early-stage CIN may aid in decreasing the numbers of CIN cases. Several novel immunoregulatory molecules have been discovered over the past few years, including the human leukocyte antigen G (HLA-G), which through interaction with its receptors exerts important tolerogenic functions. Several lines of evidence suggest that T-helper interleukin-17 (IL-17)-producing cells (Th17 cells) may play a role in antitumor immunity. However, recent reports have implicated Th17 cells and their cytokines in both pro and anti-tumorigenic processes. The aim of the study was to evaluate the roles of HLA-G and Th17 in the immunopathogenesis of CIN I.DESIGN AND SETTING:Analytical cross-sectional study with a control group using 58 cervical specimens from the files of a public university hospital providing tertiary-level care.METHODS:We examined HLA-G and IL-17 expression in the cervical microenvironment by means of immunohistochemistry, and correlated these findings with clinical and pathological features.RESULTS:There was a greater tendency towards HLA-G and IL-17 expression in specimens that showed CIN I, thus suggesting that these molecules have a contribution towards cervical progression.CONCLUSION:These findings suggest that HLA-G and IL-17 expression may be an early marker for assessing the progression of cervical lesions.

CONTEXTO E OBJETIVO:A deficiência na imunidade celular localizada parece contribuir para a patogênese e progressão das neoplasias intraepiteliais cervicais (NIC), no entanto, ainda não está totalmente esclarecido o mecanismo molecular fundamental nesse processo de progressão. A identificação de novos marcadores moleculares de prognóstico e diagnóstico das NIC em estágios precoces pode ajudar a diminuir a quantidade de casos de NIC. Várias novas moléculas com função imunorregulatória foram descobertas nos últimos anos, inclusive o antígeno leucocitário humano G (HLA-G), que, através de interação com os receptores, tem importantes funções tolerogênicas. Diversas linhas de evidência sugerem que as células T-ajudantes produtoras de interleucina-17 (IL-17, células Th17), podem desempenhar um papel na imunidade antitumoral. Porém, recentes relatos implicaram as células Th17 e suas citocinas tanto em processos pro- quanto anti-tumorigênicos. O objetivo do estudo foi avaliar o papel do HLA-G e Th17 na imunopatogênese das NIC I.TIPO DE ESTUDO E LOCAL:Estudo transversal analítico com grupo controle em 58 espécimes cervicais dos arquivos de um hospital universitário público com assistência prestada no nível terciário.MÉTODOS:Avaliamos a expressão de HLA-G e IL-17 por imunoistoquímica no microambiente cervical, associando esses achados com as características clínico-patológicas.RESULTADOS:Houve tendência aumentada da expressão de HLA-G e IL-17 em espécimes que apresentaram NIC I, sugerindo que essas moléculas têm contribuição na progressão cervical.CONCLUSÃO:Estes resultados sugerem que a expressão do HLA-G e da IL-17 pode ser um marcador precoce para avaliar a progressão das lesões cervicais.

Importância do Fator Antinuclear (FAN) em pacientes com Artrite Reumatóide Juvenil (ARJ) / Significance of Antinuclear Antibodies (ANA) in Juvenile Rheumatoid Arthritis (JRA)

Amostras de soro de 24 pacientes com Artrite Reumatoíde Juvenil (ARJ) foram utilizadas para avaliar a presença do fator antinuclear pela técnica de imunofluorescência indireta-Help-2. A presença ou näo desse auto-anticorpo foi associada com as classificaçöes existentes (pauciarticular, poliarticular ou sistêmica) contribuindo par melhor seguimento da fisiopatologia.

Importância da detecção de anticorpos antinucleares pela técnica de imunofluorescência indireta HEp-2 em pacientes com Lúpus eritematoso sistêmico / The importance of antinuclear-antibodies detection in patients with systemic lupus erythematosus by indirect immunofluorescence HEp-2 technic

Anticorpos antinucleares (ANA) constituem um grupo de auto-anticorpos dirigidos contra ácidos nucleicos e nucleoproteínas, encontrados nas colagenoses. A detecção desses auto-anticorpos é feita através de uma metodologia sorológica simples e sensível denominada técnica de imunofluorescência indireta (IFI) com células epiteliais humanas (HEp-2). Esses auto-anticorpos podem ser específicos de determinados órgãos ou sistêmicos, como ocorre em várias doenças das quais o lúpus eritematoso sistêmico (LES) é o protótipo. O objetivo deste trabalho foi realizar a pesquisa de ANA em pacientes provenientes do Hospital Universitário Onofre Lopes (HUOL) UFRN com indicação clínica de LES e outras doenças auto-imunes, como também a realização de testes sorológicos complementares (VDRL, PCR e FR). Dos 75 pacientes estudados, 22 (29,3%) obtiveram ANA pisitivo, sendo que 11 (50%) receberam diagnóstico final de LES.Em relação aos exames complementares foi observado que 18,2% dos pacientes apresentaram VDRL reativo, 81,8% PCR positiva e 18,2% FR positivo. A detecção do ANA pela IFI-HEp-2 consistiu de um método sensível para paciente com suspeita de LES e outras doenças auto-imunes.

Avaliação imunológica da leucemia mielóide aguda através da citometria de fluxo / Immunological evaluation of the acute myeloid leukemia by flow cytometry

Embora a citomorfologia ainda seja importante no diagnóstico das leucemias agudas (MA), a imunofenotipagem têm se tornado essencial no diagnóstico e acompanhamento destas deoplasias. Dentre estes métodos a citometria de fluxo tem se destacado na metodologia moderna, apresentando caracteristicas de análise multiparamétrica e quantitativa de células sanguíneas normais e leucêmicas. O objetivo deste trabalho foio de realizar estudo retrospectivo de imunofenotipagem em 38 casos de LMA. A imunofenotipagem foi realizada em constituido de CD13, CD33, CD34, CD45, CD14, CD7, CD3, CD4, CD19, CD10, HLADR e IgM. Os parâmetros hematológicos foram obtidos em contadores hematológicos e a citomorfologia em distensões sanguíneas e de medula óssea coradas peloLeishmann. Paralelamente também foram obtidas informações referentes aos doentes tais como idade e sexo, bem como dados clínicos relacionados à doença. Dos 38 individuos analisados, 23 casos eram do sexo masculino e 15 do sexo feminino. Em relação a faixa etária constatou-se um maior número de casos adultos. Com relação aos dados clínicos, observou-se que a hepatomegalia e a esplenomegalia estiveram presentes na maioria dos casos com 87,5% e 50% dos casos respectivamente.A imunofenotipagem demonstrou um perfil caracteristico de LMA com expressão de CD 13/CD33 em todos os casos, o CD34 na maioria dos casos. O CD14 foi reativo nas leucemias monociticas, tendo sido também observado negatividade aos atigenos linfóides como o CD19, CD10 e CD3 com exceção do CD7 que esteve presente em 5 casos. Em relação a citomorfologia, observou-se uma correlação direta entre a citomorfologia e a classificação FAB, havendo um predominio do tipo de mielo monocitico LMA M4 que correspondeu a 41,7% dos casos. Estes dados demonstram a importância da imunofenotipagem no diagnóstico diferencial das LMA, bem como, no acompanhamento das neoplasias.