Evaluating diagnostic accuracy of anti-tissue Transglutaminase IgA antibodies as first screening for Celiac Disease in very young children

Background: Small bowel biopsy is the gold standard for Celiac Disease (CD) diagnosis, nevertheless serum assays are the first step in ascertaining a diagnosis of CD. New ESPGHAN Criteria 2012 (European Society of Pediatric Gastroenterology Hepatology and Nutrition) suggest using exclusively anti-tissue Transglutaminase IgA antibodies (anti-tTGA) as initial approach to symptomatic subjects. The aim of our study was to evaluate the diagnostic accuracy of anti-tTGA as initial screening assay for CD in a large cohort of pediatric patients. Methods: We selected 730 subjects aged between 6. months and 4. years ("Group A") and 348 subjects younger than 2. years (which are part of the 730 subjects) ("Group B"). We performed anti-Deamidated Gliadin Peptides IgA and IgG antibodies (a-DGP IgA/IgG) and anti-tTGA assays by ELISA test. We evaluated the agreement between anti-tTGA and a-DGP IgA/IgG assays and compared the diagnostic accuracy of a-DGP IgA/IgG with that of anti-tTGA in both groups of patients. Results: There was a substantial agreement between anti-tTGA and a-DGP IgA in "Group A" and an almost perfect agreement in "Group B" the strength of agreement between anti-tTGA and a-DGP IgG was moderate in "Group A" and substantial in "Group B".anti-tTGA were more sensitive and specific than a-DGP IgA/IgG in both groups. Conclusions: anti-tTGA could be used as initial screening assay for CD in all subjects from 6. months of age according to ESPGHAN Criteria 201

Lymphocyte proliferative response to mitogenic monoclonal antibodies in systemic sclerosis. Evidence for unresponsiveness to murine monoclonal antibodies of IgG1 isotype.

Proliferative response of peripheral blood mononuclear cells to phitohemoagglutinin and anti-CD3 mitogenic monoclonal antibodies (MoAbs) of the IgG2a (OKT3) and IgG1 (PanT2, CLB T3/4.1) isotypes was studied in 39 patients with systemic sclerosis (SSc) and in 82 control subjects. The effect of IL-2 on this response was also investigated. No difference in the response to PHA and to IgG2a anti-CD3 MoAb OKT3 was seen between scleroderma patients and controls. Both the patient and control groups contained responders and non-responders to IgG1 anti-CD3 MoAbs. The percentage of non-responders was significantly higher in scleroderma patients than in controls. When purified lymphocytes from non-responder scleroderma patients were cultured with monocytes from control responders, proliferative response to IgG1 MoAbs was restored. Our results show that monocytes from patients with systemic sclerosis bear a defect leading to IgG1 unresponsiveness by T lymphocytes

Increased CD154 expression in uninfected infants born to HIV-positive mothers exposed to antiretroviral prophylaxis.

Although prevention of mother-to-child HIV transmission by antiretroviral drugs has been shown to be effective, the short- and long- term effects of treatment are not well known. Several reports suggest that antiretroviral drugs act not only by inhibiting viral replication, but also by improving anti-viral immunity. In particular, treatment with nucleoside analogues was found to increase CD40L (CD154) levels, an inducible molecule expressed on activated-T lymphocytes. The present study investigated potential immunostimulatory effects of antiretroviral treatment (ART) in uninfected HIV-exposed infants, receiving either ante- and post-natal therapy to reduce transmission rate. To this end, we analysed CD40L expression in unstimulated lymphocytes from peripheral blood samples of uninfected infants vertically exposed to HIV and subjected to ART. The CD45 panleucogating strategy was applied in flow cytometry to analyse the lymphocytes of 41 cases and 64 age-matched infants, taken as control. We found an increased CD154 expression on both CD4- and CD8-lymphocytes in ART-treated infants, compared to the controls. CD154 was apparently functional, since the expression of CD86 on monocytes was enhanced, moreover, the inhibition of CD40/CD40L interaction produced down-modulation of CD86. From these results, we conclude that CD4 and CD8 lymphocytes of HIV-exposed non infected infants, who have been exposed to antiretroviral drugs in foetal and early life, display enhanced CD154 expression and co stimulatory activity