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 2012.

Identification and characterization of a T cell growth inhibitory factor produced by K562 erythromyeloid cells.

Cells of the human erythroleukemia cell line K562 constitutively secrete a factor that inhibits human T lymphocyte proliferation induced via CD3/Ti. The factor, termed K-TIF (K562-derived T cell inhibitory factor) is produced in either the presence or absence of fetal calf serum in cultures of K562 cells and can be precipitated by 70% NH4SO4. Gel filtration chromatography on Superose 12 resin by FPLC showed that the inhibitory factor has a molecular weight of approximately 30-35 kDa. A protein of this size, metabolically labeled with [35S]methionine, specifically bound human peripheral blood mononuclear cells. Chromatofocusing with Mono P by FPLC (pH gradient 7.2-5) indicates that the inhibitory factor has an isoelectric point of 6.0-6.4.

Lack of a role of monocytes in the inhibition by monoclonal antibodies to monomorphic and polymorphic determinants of HLA class I antigens of PHA-P-induced peripheral blood mononuclear cell proliferation.

This study aimed at characterizing the mechanism(s) underlying the regulatory role of distinct determinants of HLA Class I antigens in PHA-P-induced T cell proliferation and the involvement of monocytes in this phenomenon. The anti-HLA-A2,A28 monoclonal antibodies (MoAb) CR11-351, the MoAb Q6/64 to a determinant restricted to the gene products of the I antigens HLA-B locus, and the MoAb CR10-215 and W6/32 to distinct monomorphic determinants of HLA Class I antigens were found to inhibit PHA-P-induced peripheral blood mononuclear cell (PBMC) proliferation in a dose-dependent fashion. The inhibition is specific and reflects neither inhibition of PHA-P binding to cells nor a toxic effect of the anti-HLA Class I MoAb. The latter differed in the concentration required to induce inhibition, in the influence of the concentration of PHA-P used as mitogen, in the differential effect on the donors used as a source of PBMC, and/or in the requirement of the Fc portion to induce inhibition. At variance with the information in the literature, the inhibitory effect of anti-HLA Class I MoAb on PHA-P-induced PBMC proliferation neither reflected their interaction with accessory cells nor was mediated by suppressor factors released by monocytes stimulated with PHA-P in the presence of anti-HLA Class I MoAb. Therefore, the regulatory role of HLA Class I antigens in T cell proliferation is not likely to be mediated by monocytes and/or factors released from them, but may reflect an involvement of these molecules in T cell activation pathways.

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.

Heterogeneity in the mitogenic response of peripheral blood mononuclear cells to a pan T monoclonal antibody.

Peripheral blood mononuclear cells (PBMC) from 80 normal donors were studied for their capacity to proliferate in response to Pan T2, an IgG1 monoclonal antibody (MoAb), that recognizes the CD3 complex. Forty percent of this population, regardless of sex or age, were found to be non-responders. However, the binding of MoAb Pan T2 to T cells as studied by indirect immunofluorescence was positive in all the donors. The addition of IL 1 or IL 2 to Pan T2-stimulated non-responder lymphocytes did not activate T cell proliferation, while the addition of responder monocytes restored the proliferation capacity in non-responder PBMC. The data indicate the existence of a heterogeneous responsiveness among normal individuals to a mitogenic IgG1 MoAb, and are in agreement with reports obtained using other anti-T3 MoAbs of IgG1 isotype, i.e. UCHT1, Leu4 and WT31. This defect is reported to be a function of monocytes, related to a polymorphism of Fc receptors for mouse IgG1 on human monocytic cells.

Soybean protein diets in the management of type II hyperlipoproteinaemia.

The efficacy of soybean protein treatment of stable type II hyperlipoproteinaemia was evaluated in 57 patients assigned to the following protocols: (i) substitution of animal protein with soybean protein (19 subjects) and (ii) addition of soybean protein to a standard low-lipid diet (38 subjects). After 16 weeks of treatment, plasma cholesterol was reduced by 29.5% in the first group, and by 29.9% in the second; the difference was not significant. Similarly the reduction in LDL cholesterol was not significantly different between the 2 groups (39% in the first group and 36% in the second). Plasma triglycerides fell by 11.8% and 18.2%, respectively. HDL cholesterol was not modified to any significant extent by soybean protein regimens. These results provide that the addition of soybean protein to a standard low-lipid diet is effective in inducing a significant cholesterol decrease in patients with type II hyperlipoproteinaemia.

Prevalence of impaired glucose tolerance, diabetes mellitus and ischemic heart disease in an Italian rural community. The Sanza Survey.

Coronary heart disease rates were estimated in three groups of people participating in the Sanza Survey - newly diagnosed non insulin dependent diabetics, subjects with impaired glucose tolerance and control subjects with normal glucose tolerance. The prevalence of Minnesota-coded ECG abnormalities showed a significant gradient with an approximately twofold excess in both the newly detected diabetic and impaired glucose tolerance cases over the subjects with normal glucose tolerance. The doubling of ECG ischemic changes found in subjects with impaired glucose tolerance and diabetes mellitus appeared to operate almost equally in the absence or presence of several other recognized risk factors for coronary ischemic damage. It is concluded that a relatively low degree of glucose intolerance alone may be important in determining coronary heart disease.

[Effects of 2 thymus extracts on blood levels of cholesterol and glucose in the rat]. / Influenze di due estratti timici sui livelli ematici di colesterolo e glucosio nel ratto.

The effects of two calf thymus extracts (fraction III and Tp1) on the haematic levels of cholesterol and glucose in the rat on a fat diet have been compared. The fraction III carries out a very marked decrease of cholesterolemia without changes in the levels of glycemia. On the contrary the Tp1 determines only a moderate decrease of cholesterolemia but a very marked decrease of glycemia. Thherefore these results seem both to confirm the differences between the two thymus extracts and the metabolic actions of thymus.

[In vivo effects of rapid glycemic variations on HbA1c]. / Effetti in vivo di rapide variazioni glicemiche sull'HbA1c.

The percent of variations of glycosylated haemoglobin before and after rapid glycemic increases inducted in diabetics and healthy subjects are not significant (p greater than 0,05). The same results were obtained using both the chromatographic method on Bio-Rex 70 microcolumns and the colorimetric method with 2-thiobarbituric acid. The usefulness of HbA1c as a parameter in controlling the glycemic equilibrium is confirmed.