Polymorphism in the catalytic subunit of the PI3Kγ gene is associated with Trypanosoma cruzi-induced chronic chagasic cardiomyopathy.

Chagas disease is caused by the protozoan parasite Trypanosoma cruzi. During the chronic phase of disease, while most infected people do not present symptoms, characterizing the asymptomatic form, some patients develop the cardiac form or chronic chagasic cardiomyopathy, which is considered the most severe manifestation of this disease. Considering that the activation of the PI3Kγ signaling pathway is essential for an efficient immune response against T. cruzi infection, we evaluated the PIK3CG C > T (rs1129293) polymorphism in exon 3 of this gene, which encodes the catalytic subunit of PI3Kγ. The PIK3CG CT and TT genotypes were found to be associated with an increased risk of developing the cardiac form of the disease rather than the asymptomatic or digestive forms. In conclusion, the presence of the T allele at single or double doses may differentiate the cardiac from other clinical manifestations of Chagas disease. This finding should help in further studies to evaluate the mechanisms underlying the differential association of PIK3CG in Chagas disease.

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.