Microarray and bioinformatic analysis of conventional ameloblastoma: an observational analysis

Abstract Ameloblastoma is a highly aggressive odontogenic tumor, and its pathogenesis is associated with many participating genes. Objective We aimed to identify and validate new critical genes of conventional ameloblastoma using microarray and bioinformatics analysis. Methodology Gene expression microarray and bioinformatic analysis were performed using CHIP H10KA and DAVID software for enrichment. Protein-protein interactions (PPI) were visualized using STRING-Cytoscape with MCODE plugin, followed by Kaplan-Meier and GEPIA analyses that were used for the candidate's postulation. RT-qPCR and IHC assays were performed to validate the bioinformatic approach. Results 376 upregulated genes were identified. PPI analysis revealed 14 genes that were validated by Kaplan-Meier and GEPIA resulting in PDGFA and IL2RA as candidate genes. The RT-qPCR analysis confirmed their intense expression. Immunohistochemistry analysis showed that PDGFA expression is parenchyma located. Conclusion With bioinformatics methods, we can identify upregulated genes in conventional ameloblastoma, and with RT-qPCR and immunoexpression analysis validate that PDGFA could be a more specific and localized therapeutic target.

Novel heterozygous mutation of the IL2RA gene in one Chinese girl with immunodeficiency 41 with lymphoproliferation and autoimmunity and diabetes mellitus, insulin-dependent 10: One case report and literature review / 中华内分泌代谢杂志

Objective To report a case of immunodeficiency 41 with lymphoproliferation and autoimmunity (IMD41) and type 10 insulin-dependent diabetes mellitus(IDDM10), caused by mutations of the interleukin 2 receptor α(IL2RA)gene.Methods Clinical symptoms were colleted,while IL2RA gene was sequenced.Results Here we reported a girl of 7 years and 6 months old who came to our hospital presented with lymphadenovarix for 5 years,debilitation for 2 months and alternation of hyperglycemia and hypoglycemia for 20 days. She was subsequently diagnosed with fungal pneumonia and ANCA-associated vasculitis. All exons of IL2RA gene were sequenced. c.340C>T(p.Q114X,paternal,novel mutation),c.64G>A(p.E22X,maternal) were detected. After treatments of dihydrocortisone,voriconazole combined with diabetic diet plus raw cornstarch, the pulmonary lesions reduced, autoantibodies disappeared and the blood glucose returned to normal. Literature review suggested that totally 5 IL2RA gene mutation patients were reported, the major clinical features were recurrent infection(infection of lung, skin, gastrointestinal tract) and immune abnormalities ( such as lymph node disease, autoimmune disease, hepatosplenomegaly,and diabetes mellitus). Conclusion In cases of atypical clinical symptoms, whole exon sequencing helps early diagnosis.

Polymorphisms in the TGFB1 and IL2RA genes are associated with clinical forms of leprosy in Brazilian population

BACKGROUND Leprosy is a chronic infectious disease caused by Mycobacterium leprae, and compromises the skin and peripheral nerves. This disease has been classified as multibacillary (MB) or paucibacillary (PB) depending on the host immune response. Genetic epidemiology studies in leprosy have shown the influence of human genetic components on the disease outcomes. OBJECTIVES We conducted an association study for IL2RA and TGFB1 genes with clinical forms of leprosy based on two case-control samples. These genes encode important molecules for the immunosuppressive activity of Treg cells and present differential expressions according to the clinical forms of leprosy. Furthermore, IL2RA is a positional candidate gene because it is located near the 10p13 chromosome region, presenting a linkage peak for PB leprosy. METHODS A total of 885 leprosy cases were included in the study; 406 cases from Rondonópolis County (start population), a hyperendemic region for leprosy in Brazil, and 479 cases from São Paulo state (replication population), which has lower epidemiological indexes for the disease. We tested 11 polymorphisms in the IL2RA gene and the missense variant rs1800470 in the TGFB1 gene. FINDINGS The AA genotype of rs2386841 in IL2RA was associated with the PB form in the start population. The AA genotype of rs1800470 in TGFB1 was associated with the MB form in the start population, and this association was confirmed for the replication population. MAIN CONCLUSIONS We demonstrated, for the first time, an association data with the PB form for a gene located on chromosome 10. In addition, we reported the association of TGFB1 gene with the MB form. Our results place these genes as candidates for validation and replication studies in leprosy polarisation.

Polymorphisms in Interleukin-2 and Interleukin- 7 Receptor α-Chain Genes and Human Herpes Virus-6 as Risk Factors for Multiple Sclerosis.

Aim: The aim of this study was to examine whether a Human herpes virus-6 (HHV-6) infection increases the risk of MS in individuals harboring particular cytokine receptor α- chain gene alleles. Study Design: MS patients and controls were assessed for HHV-6 DNA and for single nucleotide polymorphisms (SNPs) in their IL7RA and IL2RA genes. Place and Duration of Study: The study was carried out at the Department of Experimental Pathology, Microbiology and Immunology, American University of Beirut, between March 2011 and March 2013. Methodology: Blood samples from 100 MS patients and 100 controls were investigated for the presence of HHV-6 by nested PCR. Single nucleotide polymorphisms (SNPs) in the IL7RA and IL2RA genes were examined by restriction fragment length polymorphism. Results: HHV-6 was detected in 58% of MS patients and 32% of controls (OR = 2.935, 95% CI = 1.582-5.463, p=0.000). We did not detect a statistically significant correlation between MS and the studied rs2104286, rs12722489 SNPs in the IL2RA gene and rs6897932 SNP in the IL7RA gene. Concomitant presence of rs2104286 and HHV-6 was detected in 56% of patients and 30% of controls (OR=2.970, 95% CI=1.594-5.53, P=0.000). Similarly, rs6897932 and HHV-6 were observed in 57% of patients and 28% of controls (OR=3.409, 95% CI= 1.815-6.428, P=0.000). Therefore, double positivity moderately increased the risk of MS compared to either factor alone. HHV-6 and rs12722489 double positivity did not increase the risk of MS. Conclusion: HHV-6 infections may enhance the risk of MS in subjects with particular genetic determinants.

Genética de la diabetes mellitus tipo 1 / Genetic of type 1 diabetes mellitus

Type 1 diabetes (T1D) results from autoimmune-mediated destruction of the pancreatic beta cells, a process that is conditioned by multiple genes and environmental factors. The process that destroys the pancreatic b cells in T1D is mediated by T cells and leads to a complex phenotype influenced by multiple factors. It has been more than 30 years since the publication of the first evidence suggesting the involvement of a specific chromosomal region, HLA, in modulating the risk for T1D. HLA locus has been known for decades to contribute strongly with the attributable to genetic risk. In addition to HLA, many proposed candidate loci have been described that are associated with risk of developing the disease, including the insulin gene (INS), PTPN22,CTLA-4, PD-1, IL2-RA and IFIH1 which together do not contribute more than 15 percent of the risk. This review compiled the data on T1D genes and discusses the major genetic impact of these genetic aspects in T1D etiology.

The Enhancing IL-2R alpha mRNA Expression induces A Marked T Cel Proliferation with Interleukin-2 and Anti-CD3 mAb / 대한면역학회지

Culture of human peripheral T lymphocytes with irnmobilized anti-CD3 rnAb plus IL-2 resulted in a marked proliferation and the enhancing IL-2Ra mRNA expression. The process of the T cell activation involves a series of biochemical events which ultimately lead to the proliferation and IL-2Ra mRNA expression. Although the above results have been observed, the celluar signal mechanisms between the proliferative response and the IL-2Ra mRNA expression through T cell receptor and IL-2 receptor remains unresolved. In the present study, We have used genistein (the selective PTK inhibitor) or chronic PMA treatment (depletion of intracelluar PKC activity), to investigate the role of PTK or PKC both in a synergistic proliferation and in the enhancing IL-2Ra mRNA expression by IL-2/anti-CD3. Genistein (30 ug/ml) completely blocked IL-2 induced T cell proliferation, and inhibited anti-CD3 induced T cell proliferation (93.4%). But genistein downregulated the IL-2Ra mRNA expression by IL-2, anti-CD3 and IL-2/anti-CD3. The chronic PMA treatment failed to inhibit the proliferation and the IL-2R#u mRNA expression by IL-2 alone. But PKC depleted T cells stimulated with anti-CD3 mAb showed the decrease of the proliferation (68.6%) and IL-2Ra mRNA expression. In activated with IL-2/anti- CD3, the proliferative response showed a half of reduction, but the IL-2Ra mRNA expression were not regulated. These results demonstrate that proliferative response to IL-2 appears to be dependent on PTKs activity and independent of PKC involvement, but the IL-2Ra mRNA expression may be required another signals. PTKs and PKC activity may be important in TCR/CD3 signaling. But IL-2/anti-CD3 are coupled up different signal transduction pathways responsible for the synergistic T cell proliferation and the enhancing IL-2Ru mRNA expression.