The shared CTLA4-ICOS risk locus in celiac disease, IgA deficiency and common variable immunodeficiency.

IgA deficiency (IgAD) and common variable immunodeficiency (CVID) often co-occur in families, associating with chronic inflammatory diseases such as celiac disease (CD). ICOS (inducible co-stimulator) and CTLA4 (cytotoxic T-lymphocyte-associated protein-4) may be important in both disorders, as ICOS is necessary for Ig class-switching and CTLA4 negatively regulates T-cell activation. Linkage and association of CD with CTLA4-ICOS is well documented, we thus aimed to further pinpoint CD susceptibility by haplotype-tagging analysis. We genotyped 663 CD families from Finland and Hungary, 575 additional CD patients from Finland, Hungary and Italy; 275 Swedish and Finnish IgAD individuals and 87 CVID individuals for 14-18 genetic markers in CTLA4-ICOS. Association was found between CTLA4-ICOS and both IgAD (P=0.0015) and CVID (P=0.0064). We confirmed linkage of CTLA4-ICOS with CD (LOD 2.38, P=0.0005) and found association of CTLA4-ICOS with CD (P=0.0009). Meta-analysis of the IgAD, CVID and CD materials revealed intergenic association (P=0.0005). Disease-associated markers were associated with lower ICOS and higher CTLA4 expression, indicating that the risk haplotypes contain functional variants. In summary, we identified a novel shared risk locus for IgAD, CVID and CD, the first report of association between CTLA4-ICOS and IgAD. Association between CD and CTLA4-ICOS was also confirmed in a large European data set.

T cell regeneration in pediatric allogeneic stem cell transplantation.

Delayed and/or insufficient T cell recovery post hematopoietic stem cell transplantation (HSCT) leads to an increased risk of morbidity and mortality. We evaluated thymic function and its association with T cell regeneration post HSCT and identified factors involved in the process among pediatric stem cell transplant recipients. T cell regeneration in 66 pediatric patients was prospectively followed by naive T cell phenotyping, measuring of T cell receptor excision circles (TRECs) and expression of Foxp3 by regulatory T cells for the first 18 months post HSCT. TRECs were lower pre-HSCT in children with a malignant than non-malignant primary disease or immunosuppressed controls (P=0.001). Naive T lymphocyte reconstitution and thymic recovery were slow in the recipients of allogeneic stem cell grafts post HSCT. Infections caused by herpesviruses had a prognostic impact on mortality. Children with low TRECs had a high mortality (P=0.05) and low TRECs were also associated with extensive chronic graft-versus-host disease from 6 months onwards. Low amount of Foxp3 pre-HSCT was associated with an increased mortality post HSCT (P=0.03). Our study indicates an association between impaired T cell regeneration and thymic dysfunction and the clinical post transplant complications in pediatric allogeneic stem cell transplantation.

Performance of a new rapid whole blood coeliac test in adult patients with low prevalence of endomysial antibodies.

BACKGROUND: In coeliac disease endomysial and transglutaminase autoantibodies are directed against the human autoantigen, transglutaminase. The conventional coeliac antibody tests are performed from serum samples in centralized laboratories. AIMS: To evaluate a rapid and easy immunoglobulin A-class whole blood point-of-care test and its commercial application, the Biocard test, in coeliac autoantibody detection. METHODS: In the whole blood point-of-care test transglutaminase is liberated from the red blood cells by haemolysis. Transglutaminase antibodies, if present, complex with the liberated antigen, and are visualized. Altogether 51 biopsy-proven untreated coeliac adult patients, 48 of the same patients after treatment, and 36 controls were tested. The point-of-care test results were compared with serum endomysial and transglutaminase antibody and Biocard test results and histology. RESULTS: The whole blood point-of-care test was as sensitive (82%) as the serum endomysium test (80%) in detecting untreated coeliac disease while the serum transglutaminase antibody test was superior (88%). The tests had 100% specificity. A positive point-of-care test result seroconverted or the test reaction weakened in 90% of the treated coeliac patients. Biocard test-positive were 22 of the 24 tested untreated coeliac patients. Biocard test-negative were 15 of 19 controls. CONCLUSIONS: The whole blood rapid tests are as reliable as the conventional serological tests in detecting untreated coeliac disease and in coeliac disease diet monitoring.

Liberation of Printed Circuit Assembly (PCA) and dust generation in relation to mobile phone design in a size reduction process.

Complex electronic devices entering our recycling systems often generate losses in the whole treatment chain. For better liberation, crucial for the mechanical separation process, the devices are crushed which also generates dusts that are not recovered. This study investigated the relation between the liberation of Printed Circuit Assembly (PCA) and dust generation in the crushing process of two different types of mobile phone samples. The results revealed that the overall PCA grade in both samples was approximately 70% with around 3.4% dust generation. However, the liberation distribution of PCAs differed between mobile phones resulting in better distribution for sophisticated mobile phones due among other things to the initial size of the phones. Further, the dust fractions comprised both noble and valuable metals but also contaminants that need to be taken into account when further processing is planned. A higher gold concentrate was detected in dusts from regular phones since the protective plastic casing crushed more easily thus exposing the PCA surface for grinding.