Renata Gonçalves Resende

Association between polymorphisms in interleukin-17A and -17F genes and chronic periodontal disease.

Objective. Interleukin-17 (IL-17) is a cytokine that induces neutrophil recruitment and the release of inflammatory mediators in several inflammatory conditions; nevertheless, the involvement of IL-17 gene polymorphisms in chronic periodontitis (CP) has not been addressed yet. Our aim was to evaluate the association between periodontal status and the polymorphisms IL-17A G197A and IL-17F C7488T in subjects with CP along with their impact on levels of inflammatory mediators. Material and Methods. Genomic DNA was obtained from 30 CP patients and 30 healthy controls (HCs). IL-17A G197A and IL-17F C7488T polymorphisms were determined using PCR-RFLP. Serum and periodontal tissues were collected and processed for ELISA, myeloperoxidase (MPO), and/or microscopic analysis. Results. The frequencies of genotypes in the CP group were significantly different from those of HC. Odds ratio indicated that increased risks for CP were associated with the -197A allele, not with the -7488T allele. In addition, the -197A allele was correlated with worse clinical parameters, higher MPO activity, and increased expression of inflammatory mediators (IL-17A and IL-8) than the other genotypes. Conclusions. These results indicate that the IL-17A -197A allele is associated with increased risk for CP, likely because this genotype relates to the enhanced inflammation in periodontal tissues.

Imatinib-associated hyperpigmentation of the palate in post-HSCT patient

Pigmentation of the oral mucosa can indicate a wide range of lesions or conditions. Some drugs are associated with pigmented lesions of oral cavity. Imatinib mesylate (Gleevec(®)) is a protein inhibitor used in the management of several hematological malignancies associated with dermatological side effects, like hyperpigmentation. We report the case of a 38-year-old male post-HSCT patient who had been using imatinib mesylate for over 5 years and presented with blue pigmentation on the hard palate, the left side of the nose and both ear lobes. The differential diagnosis of hyperpigmented lesions in the oral mucosa is also presented.

Saliva as a source of HCMV DNA in allogeneic stem cell transplantation patients.

OBJECTIVE The purpose of this study was to investigate the use of saliva for the identification of human cytomegalovirus (HCMV) in allogeneic hematopoietic stem cell transplant patients by real time PCR compared with blood. MATERIALS AND METHODS Saliva and blood samples were sampled weekly in 30 allogeneic hematopoietic stem cell transplant patients until 100 days after transplant. Total genomic DNA, extracted from saliva and whole-blood samples, was used for HCMV real time PCR. Nonparametric tests were performed, and P value <or=0.05 was considered statistically significant. RESULTS Human cytomegalovirus DNA load in saliva showed a high correlation with viral DNA in the blood (R = 0.858; P < 0.0001). Blood DNA levels also correlated with HCMV antigenemia (R = 0.773; P < 0.0001). The HCMV levels in saliva (P = 0.015) and blood (P = 0.008) showed higher levels at the beginning of antiviral treatment, with clear reduction after this period. Saliva showed earlier HCMV reactivation than blood detected by real time PCR and antigenemia assay in 11 out of 22 subjects. CONCLUSIONS This study shows that the real time PCR test could be useful to identify HCMV DNA in saliva and to monitor patients at risk of cytomegalovirus disease after allogeneic hematopoietic stem cell transplant. However, further studies are necessary to confirm this data.

Association Between IL1B (+3954) Polymorphisms and IL-1β Levels in Blood and Saliva, Together with Acute Graft-Versus-Host Disease

Graft-versus-host disease (GVHD) is associated with morbidity and mortality in the recipients of allogeneic hematopoietic stem cell transplants (allo-HSCTs). Interleukin-1β (IL-1β) is a potent inflammatory mediator involved in different inflammatory conditions. Therefore, we aimed to investigate the association of IL1B gene polymorphism in recipients and donors in cases in which acute GVHD (aGVHD) has been reported and the impact of this gene polymorphism on the level of cytokines in the blood and saliva. Fifty-eight consecutive allo-HSCT recipients and their donors were prospectively studied. Saliva and/or blood samples were obtained from the recipients and donors to identify the IL1B gene polymorphism, and cytokine levels were assessed by ELISA. Samples were collected weekly from 7 days before transplantation (day -7) to 100 days after allo-HSCT (day+100), for a total of 16 weeks or until death. aGVHD occurred in 27 individuals evaluated. A significant association was identified between the IL1B polymorphism in the donor and aGVHD development in the corresponding recipients. However, no significant association was detected between the IL1B polymorphism in recipients and the development of aGVHD. In the recipients who were diagnosed with aGVHD, the level of IL-1β in the saliva and blood were increased. In the saliva, IL-1β levels increased progressively from the time before the diagnosis of aGVHD until weeks after the diagnosis, whereas in the blood, IL-1β peak levels could be observed within the time allotted for diagnosis, followed by a decrease in the levels. In addition, we observed a significant association between the IL1B genotype of the recipient (CC) and high IL-1β levels in the saliva at week 13. In conclusion, IL-1β could be considered a useful predictor of aGVHD development.

Oral cGVHD screening tests in the diagnosis of systemic chronic graft-versus-host disease

To determine the diagnostic properties of oral manifestations and histological features of graft-versus-host disease (GVHD) screening tests in the diagnosis of systemic chronic graft-versus-host disease (cGVHD). Sixty patients having undergone allogeneic haematopoietic stem cell transplantation were selected. The patients were submitted to a clinical oral examination to assess symptoms and clinical changes in the oral mucosa. Histopathologic analysis of the lower lip oral mucosa (LLOM) and salivary glands (SG) was also performed. Systemic cGVHD was used for a comparison to oral cGVHD. The accuracy of oral cGVHD tests was low for all methods (58.4% and 52.6% for white lesions and white/red lesions, respectively, in the clinical analysis; 50.4% for the presence of oral pain; and 66.8% and 55.1% for LLOM and SG histopathologic tests, respectively). However, the presence of oral pain had good diagnostic properties [specificity: 100.0, 95% confidence interval (CI): 88.0–100.0; positive predictive value (PPV): 100.0, 95% CI: 94.4–100.0; and negative predictive value (NPV): 72.0, 95% CI: 57.3–83.3]. Moreover, SG alterations revealed by the histopathological analysis also exhibited good diagnostic properties (sensitivity: 98.6, 95% CI: 81.5–99.8; PPV: 71.1, 95% CI: 62.1–79.7; NPV: 85.9 95% CI: 32.9–99.4). The clinical severity of oral lesions and histophatological changes in the LLOM did not exhibit adequate diagnostic properties, whereas both oral pain and SG histopathological analysis exhibited adequate properties for the diagnosis of systemic cGVHD. Histological changes in lip oral mucosa and salivary glands together with a clinical manifestation of the disease in the oral mucosa can be useful to determining the systemic cGVHD.

IL-17 Genetic and Immunophenotypic Evaluation in Chronic Graft-versus-Host Disease

Although interleukin-17 (IL-17) is a recently discovered cytokine associated with several autoimmune diseases, its role in the pathogenesis of chronic graft-versus-host disease (cGVHD) was not established yet. The objective of this study was to investigate the association of IL17A and IL17F genes polymorphisms and IL-17A and IL-17F levels with cGVHD. IL-17A expression was also investigated in CD4+ T cells of patients with systemic cGVHD. For Part I of the study, fifty-eight allo-HSCT recipients and donors were prospectively studied. Blood samples were obtained to determine IL17A and IL17F genes polymorphisms. Cytokines levels in blood and saliva were assessed by ELISA at days +35 and +100 after HSCT. In Part II, for the immunophenotypic evaluation, eight patients with systemic cGVHD were selected and the expression of IL-17A was evaluated. We found association between recipient AA genotype with systemic cGVHD. No association was observed between IL-17A levels and cGVHD. Lower IL-17A levels in the blood were associated with AA genotype. In flow cytometry analysis, decreased expression of IL-17A was observed in patients with cGVHD after stimulation. In conclusion, IL-17A may have an important role in the development of systemic cGVHD.

Análise sociodemográfica e clínica de pacientes submetidos ao transplante alogênico de células-troncos hematopoiéticas

Resumen pt: Objetivo: Descrever os achados clinicos e sociodemograficos dos pacientes submetidos ao transplante de celulas-tronco hematopoieticas (TCTH) e encaminhad...

Oral Leukoplakia in a Patient With Fanconi Anemia: Recurrence or a New Primary Lesion?

l m H Fanconi anemia (FA) is a rare autosomal recessive disease that was first described by Guido Fanconi in 1927, and it has a birth incidence of approximately 3 per 1 million. This disease is characterized by short tature, various congenital abnormalities, and progresive bone marrow failure, leading to death or the need or hematopoietic stem cell transplantation (HSCT). Patients with FA have a short life expectancy, mainly because they develop malignancies such as leukemia and oral squamous cell carcinomas at a young age. The cancer susceptibility noted in patients with FA is associated with a defect in the ability to maintain the

DNA methylation patterns of genes related to immune response in the different clinical forms of oral lichen planus

BACKGROUND The oral lichen planus is a chronic inflammatory disease. Although its aetiology is not well understood, the role of T lymphocytes in its inflammatory events is recognised. Identifying the epigenetic mechanisms involved in the pathogenesis of this immune-mediated condition is fundamental for understanding the inflammatory reaction that occurs in the disease. The purpose of this work was to evaluate the methylation pattern of 21 immune response-related genes in the different clinical forms of oral lichen planus. METHODS A cross-sectional study was performed to analyse the DNA methylation patterns in three distinct groups of oral lichen planus: (i) reticular/plaque lesions; (ii) erosive lesions; (iii) normal oral mucosa (control group). After DNA extraction from biopsies, the samples were submitted to digestions by methylation-sensitive and methylation-dependent enzymes and double digestion. The relative percentage of methylated DNA for each gene was provided using real-time polymerase chain reaction arrays. RESULTS Hypermethylation of the STAT5A gene was observed only in the control group (59.0%). A higher hypermethylation of the ELANE gene was found in reticular/plaque lesions (72.1%) compared to the erosive lesions (50.0%). CONCLUSION Our results show variations in the methylation profile of immune response-related genes, according to the clinical type of oral lichen planus after comparing with the normal oral mucosa. Further studies are necessary to validate these findings using gene expression analysis.

Cytokine Production and Human Cytomegalovirus Load in Allogeneic Hematopoietic Stem Cell Transplantation Outcome

Objective: To investigate the impact of cytokine levels (IL-1β, IL-6, IL-10, IFN-γ and TNF-α) and Human cytomegalovirus (HCMV) load in the saliva and blood on the survival of allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients.