Polymorphisms at the IL17A and IL17RA Genes are Associated with Prognosis of Papillary Thyroid Carcinoma.

BACKGROUND: Interleukin (IL)-17A has a dual role in tumor immunity, promotes anti-tumor responses and facilitates angiogenesis by interacting with IL-17 receptor A (IL-17RA). Although IL-17A has been associated with the pathogenesis of papillary thyroid carcinoma (PTC), the nucleotide variability at the IL17A and IL17RA genes is still poorly characterized. AIM: To assess the contribution of the IL17A (-197 G >A, rs2275913) and IL17RA (-947 A >G, rs4819554) single nucleotide polymorphisms (SNP) on the development and progression of PTC and on IL-17 plasma levels. METHODS: We studied 188 PTC patients and 170 healthy controls. SNPs were identified using PCR-amplified DNA and restriction fragment length polymorphism (RFLP) techniques. Plasma levels of IL-17A was evaluated in 83 PTC patients using ELISA. Statistical analyses were performed to evaluate the associations between SNPs and clinicohistopathological features of PTC and IL-17A levels. RESULTS: No significant difference was observed regarding the allele and genotype distributions of both SNPs between PTC patients and controls. The IL17A GA was associated with poor biochemical and structural incomplete response to therapy, whereas no influence over the IL-17A expression was observed. The IL17RA AG was significantly associated with small-sized tumors, initial tumor stage at diagnosis and better response to therapy. CONCLUSIONS: The IL17A SNP may predict an aggressive manifestation of PTC, whereas the IL17RA SNP was associated with a more favorable clinical outcome.

HLA-E gene polymorphisms in chronic hepatitis C: Impact on HLA-E liver expression and disease severity.

Hepatitis C virus usually produces chronic infection and liver damage. Considering that: i) the human leukocyte antigen-E (HLA-E) molecule may modulate the immune response, and ii) little is known about the role of HLA-E gene variability on chronic hepatitis C, we studied the impact of HLA-E polymorphisms on the magnitude of HLA-E liver expression and severity of hepatitis C. HLA-E variability was evaluated in terms of: i) single nucleotide polymorphism (SNP) alleles and genotypes along the gene (beginning of the promoter region, coding region and 3'UTR), and ii) ensemble of SNPs that defines the coding region alleles, considered individually or as genotypes. The comparisons of the HLA-E variation sites between patients and controls revealed no significant results. The HLA-E + 424 T > C (rs1059510), +756 G > A (rs1264457) and + 3777 G > A (rs1059655) variation sites and the HLA-E*01:01:01:01 and HLA-E*01:03:02:01 alleles, considered at single or double doses, were associated with the magnitude of HLA-E liver expression in Kupfer cell, steatosis, inflammatory activity and liver fibrosis. Although these associations were lost after corrections for multiple comparisons, these variable sites may propitiate biological clues for the understanding of the mechanisms associated with hepatitis C severity.

HLA-G liver expression and HLA-G extended haplotypes are associated with chronic hepatitis C in HIV-negative and HIV-coinfected patients.

Chronic hepatitis C virus (HCV) infection induces liver damage and the HCV/Human Immunodeficiency Virus (HIV)-coinfection may further contribute to its progression. The HLA-G molecule inhibits innate and adaptive immunity and may be deleterious for chronically virus-infected cells. Thus we studied 204 HCV-mono-infected patients, 142 HCV/HIV-coinfected patients, 104 HIV-mono-infected patients and 163 healthy subjects. HLA-G liver expression was similarly induced in HCV and HCV/HIV specimens, increasing with advanced fibrosis and necroinflammatory activity, and with increased levels of liver function-related enzymes. Plasma soluble HLA-G (sHLA-G) levels were higher in HCV/HIV patients compared to HCV, HIV and to healthy individuals. sHLA-G continued to be higher in coinfected patients even after stratification of samples according to degree of liver fibrosis and necroinflammatory activity when compared to mono-infected patients. Some HLA-G gene haplotypes differentiated patient groups and presented few associations with liver and plasma HLA-G expression. HLA-G thus may help to distinguish patient groups.

Human Antigen Leucocyte (HLA)-G and HLA-E are differentially expressed in pancreatic disorders.

BACKGROUND: Little information is available regarding the expression of the immunomodulatory Human Leukocyte Antigen (HLA)-G and -E molecules in pancreatic disorders. AIM: To analyze HLA-G and -E expression in specimens of alcoholic chronic pancreatitis (ACP), idiopathic chronic pancreatitis (ICP), type 1 (T1D) and type 2 diabetes (T2D) and in histologically normal pancreas (HNP). METHODS: HLA-G and -E expression (ACP = 30, ICP = 10, T1D = 10, T2D = 30 and HNP = 20) was evaluated by immunohistochemistry in three different areas (acini, islets and inflammatory infiltrate). RESULTS: Acini and islets from HNP specimens exhibited higher HLA-G and -E expression compared to corresponding areas from all other patient groups. In inflammatory infiltrate, HLA-G and -E expression was observed only among the pancreatic disorders. We observed higher HLA-G and -E expression in acini from T2D compared to ACP, as well as higher HLA-G expression compared to ICP. CONCLUSION: The decreased expression of HLA-G and -E in islets and acini together with the expression of these molecules in the inflammatory infiltrating cells were shared features among chronic inflammatory and autoimmune pancreatic disorders evaluated in this study, possibly reflecting tissue damage.

A straightforward genotyping of the relevant IL28B SNPs for the prediction of hepatitis C treatment outcome.

A sustained virological response is not achieved by a significant proportion of chronic hepatitis C patients treated with interferon-based regimens. Due to the associated side effects and high costs, therapy response markers have been thoroughly sought. Two Single Nucleotide Polymorphisms (SNPs), rs12979860 and rs8099917, which are located upstream from the IL28B gene, have been remarkably described to have a strong association with treatment efficacy. The aim of this study was to develop a straightforward method for genotyping such polymorphisms. A Polymerase Chain Reaction (PCR) followed by enzymatic restriction of amplicons was established for SNPs genotyping. Online computation resources were employed for retrieving reference sequences, such as the selection of oligonucleotides and restriction enzymes. Two pairs of primers were designed and validated for the amplification of segments encompassing rs12979860 (694bp) and rs8099917 (496bp) with common thermocycling parameters. The endonucleases Hpy166II and BsrDI were selected and used for allelic discrimination related to rs12979860 (C/T) and rs8099917 (T/G), respectively. The expected electropherotypes were confirmed for all possible genotypes in 75 blood samples. In addition, the results were validated by sequencing. The method constitutes a simple and reliable assay, which may be readily available for genotyping of rs12979860 and rs8099917 in laboratories that support hepatitis C treatment centers.