Graves' disease (GD) is an autoimmune thyroid disease. Multiple genetic factors are believed to be involved in its pathogenesis, but the factors are largely unknown, except for sex (female disease preponderance) and the role of human leukocyte antigen (HLA) genes on chromosome 6. To understand the mechanisms underlying the development of GD, a search for non-HLA-linked genes is crucial, and we tested several candidate genes, including the CTLA-4 gene on chromosome 2q33. CTLA-4 molecules may either facilitate or down-regulate the second signal to T-cells, which is provided by the interaction between the two accessory molecules CD28 and B7. One hundred and thirty-three Caucasian patients (26 males) with GD and 85 local controls were included in this study. Polymerase chain reaction was used to amplify DNA containing the (AT)n repeat within the 3'-untranslated region of exon 3 of the CTLA-4 gene. The 5'-forward primer was radiolabeled, and amplified products were resolved on 5-7% sequencing gels. All subjects were previously typed for HLA class II alleles. Twenty-one alleles were observed with sizes ranging from 88-134 basepairs. In the association analysis, the genotype frequencies between GD patients and controls differed significantly (P = 0.012), and the difference was attributable to a higher frequency of the 106-basepair allele among patients (relative risk, 2.82). When the patients were subdivided with respect to sex and HLA, the phenotype frequencies of allele 106 was higher in the female patients with protective HLA specificities (DQA1*0201 positive/DQA1*0501 negative) than in those with susceptible HLA specificities (DQA1*0201 negative/DQA1*0501 positive; 81.8% vs. 45.5%; P = 0.026). The CTLA-4 gene or a closely associated gene (including CD28) confers susceptibility to GD. This association may be more important in female patients with protective HLA specificities, who otherwise would be at low risk of developing the disease.

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IntroductionCardiopulmonary bypass (CPB) surgery is considered one of the most frequent surgical procedures in which acute kidney injury (AKI) represents a frequent and serious complication. The aim of the present study was to evaluate the efficiency of neutrophil gelatinase-associated lipocalin (NGAL) as an early AKI biomarker after CPB in pediatric cardiac surgery.Material and methodsThe study included forty children aged 2 to 78 months undergoing CPB. They were divided into group I: patients who suffered AKI grades II and III; and group II: patients who did not develop AKI or at risk. Peripheral venous blood was withdrawn pre- and post-operatively for serial measurements of NGAL and creatinine. Statistical analysis was performed using Statistical Package for Social Sciences version 14.ResultsMean plasma NGAL levels showed highly significant elevations in group I patients at 2, 12, and 24 h after surgery (p < 0.0001) compared to group II. Significant correlations were found between NGAL and creatinine at different time intervals. Highly significant correlations (p < 0.0001) were found between plasma NGAL and AKI at 2, 12 and 24 h after surgery. A cut-off level of 100 ng/ml at 2 h, and 125 ng/ml at 12 h post-operatively both recorded the highest accuracy, being 95% accurate, with sensitivity of 100% and 89.5% respectively, and specificity of 90.5% and 100% respectively.ConclusionsThis study showed that plasma NGAL could be used as an early biomarker for detection of AKI following CPB. We recommend further studies on a wider scale to validate the current study results.

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The circulating anti-parasite antibody response against Giardia lamblia in symptomatic and asymptomatic Egyptian children with confirmed giardiasis was examined. Symptomatic patients were identified using the following criteria: presence of only G. lamblia cysts in the feces, and one or more of the following symptoms, diarrhea, abdominal pain, loss of weight, vomiting and/or nausea, and abdominal distention. The anti-parasite humoral response was measured using indirect immunofluorescence (IFA), ELISA, and immunoblotting. There was a significant difference in the anti-parasite antibody response measured by IFA of asymptomatic and symptomatic patients, in which more than 34% of the asymptomatic patients had a titer equal to or less than 1:500, and more that 29% of the symptomatic patients had a titer of 1:8,000 or higher. The circulating anti-parasite total IgM and IgA but not IgG, measured by ELISA, was significantly higher in symptomatic than in asymptomatic patients, and were related to higher cyst output observed in symptomatic individuals. Although total anti-parasite IgG response was similar in symptomatic and asymptomatic patients, the analysis of the IgG isotype responses revealed that both IgG1 and IgG3 were significantly higher in symptomatic patients. The antigen recognition by anti-parasite IgM, IgA, IgG1, and IgG3 of symptomatic and asymptomatic individuals, determined by immunoblotting, was heterogeneous and revealed only minor differences in the response of the two groups.