HLA class I haplotypes in families of children with coeliac disease.
(65/1975)
The purpose of the study was the analysis of HLA-AB haplotypes frequency in the families of children with coeliac disease. Haplotypes present in 46 probands' families including 69 affected children, 49 healthy siblings and 91 parents were verified. HLA antigens were typed by Terasaki and McClelland's routine two-step-microcytotoxic assay in NIH modification. Among 138 haplotypes, the following were significantly more frequent in affected children: HLA-A1-B8 (3116 x 10(4)), HLA-A3-B8 (290 x 10(4)) and HLA-A2-B8 (217 x 10(4)). Total frequency of haplotypes including HLA-B8 antigen in comparison to control population equalled 3986 x 10(4) vs. 763 x 10(4). HLA-A1-B8 haplotype frequency was twice lower in probands' healthy siblings and parents, equalling 1837 x 10(4) and 1868 x 10(4), respectively. Highly significantly more frequent HLA-A1-B8 haplotype found in probands' families may indicate the correlation between inherited gene products and increased risk of coeliac disease incidence. (+info)
Estimation of antithyroid antibodies occurrence in children with coeliac disease.
(66/1975)
INTRODUCTION: The coexistence of coeliac disease (CD) and the diseases of autoimmune origin is often discussed in literature. In this study the evaluation of antithyroid antibodies (antimicrosomal-TMA, anti-thyreoglobulin-ATG, thyroid peroxidase antibodies anti-TPO) occurrence against clinical and laboratory determinants of thyroid function is demonstrated in children with coeliac disease. MATERIAL AND METHODS: The study was conducted on 34 IgA-EmA positive children; control group consisted of 28 children with negative screening tests for coeliac disease. RESULTS: In both groups, the level of antithyroid antibodies (TMA, ATG, anti-TPO) and determinants of thyroid gland function (TSH, fT3, fT4) were evaluated; USG examination of thyroid gland was also performed. Elevated titres of antithyroid antibodies observed in children with coeliac disease (41.1%) in comparison to control group (3.56%) indicate the need for performing the screening tests for antithyroid antibodies in children with CD. (+info)
A family study of coeliac disease.
(67/1975)
Thirteen of 141 cases (9 percent) of overt, biopsy proven coeliac disease had a definitely affected relative. The pattern of inheritance in these families is compatible with an incompletely penetrant autosomal dominant gene. There was a female preponderance in the adults and the sporadic cases, but not in the children or the familial cases. The series included a pair of concordant and probably monozygotic twins. The authors believe that coeliac disease, as defined at present, is a heterogeneous condition. (+info)
Molecular dissection of the tissue transglutaminase autoantibody response in celiac disease.
(68/1975)
Celiac disease (CD) is an intestinal malabsorption characterized by intolerance to cereal proteins accompanied by immunological responses to dietary gliadins and tissue transglutaminase, an autoantigen located in the endomysium. Tissue transglutaminase belongs to the family of enzymes that catalyze protein cross-linking reactions and is constitutively expressed in many tissues as well as being activated during apoptosis. The role of gliadins in eliciting the immune response in CD and how transglutaminase is linked to the primary reaction are still unclear. In this work, we report the production and analysis of six phage Ab libraries from the peripheral and intestinal lymphocytes of three CD patients. We were able to isolate Abs to transglutaminase from all intestinal lymphocytes libraries but not from those obtained from peripheral lymphocytes. This is in contrast to Abs against gliadin, which could be obtained from all libraries, indicating that the humoral response against transglutaminase occurs at the local level, whereas that against gliadin occurs both peripherally and centrally. Abs from all three patients recognized the same transglutaminase epitopes with a bias toward the use of the V(H)5 Ab variable region family. The possible role of these anti-transglutaminase Abs in the onset of CD and associated autoimmune pathologies is discussed. (+info)
Increased intestinal intra-epithelial T lymphocytes in primary glomerulonephritis: a role of oral tolerance breakdown in the pathophysiology of human primary glomerulonephritides?
(69/1975)
BACKGROUND: There is increasing evidence that some organ-specific and generalized autoimmune diseases in humans might be related to a breakdown of oral tolerance. We explored this hypothesis in human primary glomerulonephritides. We prospectively counted intraepithelial T lymphocytes in the duodenal mucosa (as a marker of rupture of oral tolerance), together with IgA1 and IgA2 mucosal plasma cells, in patients with primary glomerulonephritides. METHODS: We investigated eight adults with immune-complex glomerulopathy (membranous nephropathy+membranoproliferative glomerulonephritis), 16 adults with an idiopathic nephrotic syndrome, and 25 adults with IgA nephropathy. Patients with glomerulonephritides were compared to two control groups: group 1 consisted of nine healthy adults; group 2 comprised five adults with coeliac disease before dietary gluten withdrawal or during a clinical relapse related to gluten ingestion. (The latter disease is associated with increased numbers of intraepithelial T lymphocytes, and a breakdown of oral tolerance to gliadins is involved in the pathogenesis of coeliac disease). Duodenal fibroscopy was performed under neuroleptanalgesia. Four to six endoscopic biopsy specimens were taken from the second duodenum. Intraepithelial T lymphocytes were blindly counted on paraffin sections stained with haematein-eosin-saffron (HES), within the epithelium of a villus in a zone with at least 100 cells. Mucosal IgA1 and IgA2 plasma cells were blindly counted in a mucosal tissue unit by using specific mouse monoclonal antibodies directed against IgA1 and IgA2, with alkaline phosphatase anti-alkaline phosphatase (APAAP) revelation. As values were not normally distributed, we used non-parametric analysis of variance with the Kruskal-Wallis test, and compared median values by using the non-parametric Mann-Whitney test. RESULTS: Intraepithelial T lymphocytes were significantly more abundant in patients with primary glomerulonephritides and coeliac disease than in healthy controls (P < 0.0001 in the Kruskal-Wallis test): healthy controls, median 11 (range 4.65-16); immune complex glomerulopathy, 27.45*** (15-93); idiopathic nephrotic syndrome, 16.5** (9-26.5); IgA nephropathy, 26.10*** (11.3-47.5); coeliac disease, 55*** (20-80) (*P <0.05; **P <0.01; ***P < 0.005, Mann-Whitney test). No difference was found in the number of duodenal IgA1 and IgA2 plasma cells between controls and patients with primary glomerulonephritides. IgA1 and IgA2 plasma cells were increased in patients with coeliac disease. CONCLUSION: The significant increase in intestinal intraepithelial T lymphocytes in primary glomerulonephritides suggests a pathophysiological role of oral tolerance breakdown. (+info)
Limitations of xylose tolerance test as a screening procedure in childhood coeliac disease.
(70/1975)
The usefulness of the xylose tolerance test as a screening procedure for coeliac disease has been reassessed in 54 children with suspected coeliac disease. 5- and 24-hour urinary excretion rates of xylose were of no value in discriminating between patients with and without coeliac disease; similarly, the 3-hour blood xylose concentration was nondiscriminatory. Three (15-8%) patients with subtotal villous atrophy and 8 (61-5%) with partial villous atrophy due to coeliac disease had one-hour blood xylose values which fell within the normal range. The effect of withdrawal or reintroduction of dietary gluten on sequential one-hour blood xylose levels was variable and generally unhelpful in predicting those patients who developed gluten-induced mucosal changes. The results of the present study emphasize the serious limitations of the xylose tolerance test as a screening procedure in childhood coeliac disease. It is recommended that the use of the urinary xylose test should be abandoned in the paediatric population. A normal one-hour blood xylose value does not exclude a diagnosis of coeliac disease even in young children who have never received a gluten-free diet. A clinical suspicion of coeliac disease remains the most important single factor in deciding whether to preform a jejunal biopsy. (+info)
Humoral and cellular immune responses in gluten-treated suckling or hand-fed rats.
(71/1975)
We analyzed the immune response to gliadin in suckling rats and rats hand-fed with an artificial milk formula, an animal model of gluten enteropathy. Animals of both groups were intragastrically given either gliadin or albumin (control animals) or gliadin from birth till day 55. When compared to the controls, spleen lymphocytes from both groups of gliadin-treated rats cultivated in vitro exhibited a significant increase of spontaneous 3H-thymidine incorporation. Moreover, the proliferation of spleen and mesenteric lymph node (MLN) lymhocytes from both groups of gliadin-treated suckling and hand-fed rats was specifically increased by the in vitro gliadin challenge. Spleen B cells from gliadin-treated rats spontaneously produced higher amounts of gliadin-specific antibodies than those from the controls, however, in vitro stimulation by gliadin caused no further increase in antibody production. Apoptotic DNA fragmentation in MLN cells was higher in gliadin-treated rats than in albumin-treated ones, independently of the milk diet during the suckling period. (+info)
Detection of continuing gluten ingestion in treated coeliac patients.
(72/1975)
To assess the incidence and effects of continuing gluten ingestion in coeliac disease 51 adult coeliac patients were studied after four to 132 (mean 63) months on a prescribed gluten-free diet. Each patient completed a prospective dietary questionnaire, underwent a repeat jejunal biopsy, and gave serum for gluten antibody estimation. Altogether 65% of patients were still ingesting gluten, often inadvertently. Direct questioning on dietary habits had failed to uncover most of this consumption. The gluten antibody test proved a useful screening test for detecting continuing gluten ingestion and patients with both persistent subtotal villous atrophy and gluten antibodies were almost certain to be taking large amounts ( more than 2 g/day). The presence of persistent partial villous atrophy was found, however, to be an unreliable guide to gluten intake. (+info)