[Immunohistochemical study of the apoptotic and proliferative mechanisms in the intestinal mucosa during coeliac disease]. / Imunohistochemická studie mechanismu apoptózy a proliferace ve sliznici tenkého streva u celiakální sprue.

Mechanisms leading to morphological changes of the small intestine during coeliac disease are not yet completely recognized, however, two main processes have been suggested recently: remodelling of mucosa by matrix metalloproteinases, and mucosal atrophy by apoptosis. The aim of this study was to analyze the expression of proteins regulating apoptosis and some markers of proliferation in the mucosa of the small intestine of children with active (ACD) and latent form (LCD) of coeliac disease (CD). Intestinal biopsies of 43 children with ACD and LCD were analyzed by standard indirect immunohistochemical technique for Fas, Fas ligand (Fas-L), tissue transglutaminase (tTG), Bcl-2, Bid, glutathione S-transferase (GST), CAS 3, CAS 8, PARP, Ki-67, Topoisomerase IIa, PCNA expression. We found significantly lower numbers of Fas-expressing enterocytes in ACD patients than in LCD patients and controls. The number of Fas-positive mucosal lymphocytes was decreased in ACD when compared with LCD. Fas-L expression in enterocytes and mucosal lymphocytes was higher in ACD and LCD compared to controls. We found significantly more Bcl-2 negative lymphocytes in ACD than in LCD and controls. Bid expression in enterocytes was higher in LCD compared to ACD and controls. In intraepithelial lymphocytes, there was higher Bid expression in LCD than in ACD and controls compared to expression in mucosal lymphocytes, where was found higher number of positive cells in controls than in ACD and LCD. Expression of CAS 8 in mucosal lymphocytes was significantly higher in ACD compared to LCD. The expression of tTG in extracellular matrix and basal lamina was significantly higher in LCD and ACD when compared to controls. Expression of tTG was higher in the group of ACD and LCD in the enterocytes and in the lymphocytes. Our findings showed that Fas/Fas-L, Bcl-2, and CAS 8 may be involved in modulation of apoptosis during CD. Increased apoptotic elimination of IEL in LCD can partially explain preservation of the normal villous architecture. Increased tTG expression may be an early sign of increased apoptosis or may be related to its role in CD pathogenesis.

[Celiac disease and fertility disorders in women]. / Celiakie a poruchy plodnosti u zen.

OBJECTIVE: To determine incidence of subclinical forms of celiac disease in women with decreased fertility. DESIGN: Screening test. SETTING: Department of Gynecology and Obstetrics, University Hospital, Palacký University, Olomouc. METHODS: 137 patients with fertility problems were included to the study. There were divided into two groups, patients with infertility and patients with repeated pregnancy loss. Screening test for celiac disease, serum level of antibodies tissue transglutaminase (tTGA) were performed in all of them. Positive test was confirmed by serological level of anti endomysium antibodies (EmA) and final diagnosis of silent celiac disease was done by enterobiopsy. RESULTS: Celiac disease was found in two infertile patients (1.67%). In one patient the silent form was diagnosed by enterobiopsy. The second disease was latent form. In patients with repeated pregnancy loss we did not observe positive screening test. CONCLUSION: We confirmed higher incidence of celiac disease in women with impaired fertility.

[Occurrence of celiac disease in siblings and offspring of patients with celiac disease]. / Výskyt celiakie u sourozencu a potomku nemocných s celiakií.

BACKGROUND: Incidence of the coeliac disease in our population is 0.3 to 0.5%, however, in direct relatives of patients with coeliac disease incidence rises up to 5-15%. Though the disease in not always clinically manifested, it can be identified by serologic screening. METHODS AND RESULTS: 96 patients treated for active coeliac disease and their 130 siblings were examined. In four of 130 siblings the disease clinically manifested and was confirmed with finding of enteropathy of jejunal mucosa. In 14 out of 126 asymptomatic siblings endomysial antibodies were identified and in 11 of them enteropathy was diagnosed. Coeliac disease was diagnosed in 15 (11.5%) persons from 130 siblings. Also 74 offsprings of 43 parent patients were examined. In four of them the coeliac disease manifested clinically and was later confirmed with finding of enteropathy. Antiglidin antibodies were tested in 45 asymptomatic offsprings with 6 positive results. Endomysial antibodies were tested in 25 asymptomatic offsprings with one positive result. Villous atrophy of jejunal mucosa was found in four asymptomatic offsprings. Coeliac disease was diagnosed in 8 (11.5%) persons from 74 offsprings. CONCLUSIONS: Coeliac disease represent a major risk for the patient's direct relatives. Goal-directed examination and the early diagnosis of the disease in childhood may help to prevent impairments in the development of the child and possible complications later.

[Celiac disease as a cause of short stature in children]. / Celiakie jako prícina malého vzrustu u detí.

BACKGROUND: Growth retardation may be the only clinical manifestation of undiagnosed chronic intestinal disease. Therefore we have to consider also this etiology in the differential diagnosis of classical causes of short stature in children with typical clinical and laboratory findings. METHODS AND RESULTS: Among 168 patients aged 5.5-17.2 years up to June 1, 1993 on the records of the Paediatric Clinic in Olomouc on account of marked growth retardation (< or = 2 SDS) associated with retarded bone age were eight children where based on screening for antigliadin antibodies the suspicion of coeliac disease was expressed. By introduction of a gluten-free diet the growth rate improved markedly in almost all patients already during the first six months. After a one-year follow-up it increased to 9.0 +/- 1.1 cm from 3.9 +/- 1.3 cm, and concurrently a corresponding progression of ossification occurred. An exception was only a 14-year-old girl who did not comply and did not adhere to the diet. CONCLUSION: In the early diagnosis of oligosymptomatic coeliac disease with a low growth rate as the dominant symptom a key role is played by assessment of antibodies against gliadin. If the results are positive, enterobiopsy is indicated which alone can confirm the diagnosis. Dietetic provisions (a gluten-free diet) improve the growth rate and bone maturation.

Polymorphism of the 5' flanking region of the HLA-DQA1 gene in coeliac disease.

Coeliac disease (CD) is associated with particular HLA genotypes. The susceptibility gene (or genes) has been mapped to the class II region, most probably to the DQ loci. Polymorphism of the upstream promoter region of the DQA1 gene (QAP) has been recently reported. At least ten variants or QAP alleles have been found, some of which are present in the cis-acting regulatory sequences. Allelic differences in DQ molecule expression may play a role in susceptibility to CD. We investigated the QAP polymorphism in 102 CD patients and 142 unrelated healthy controls of Czech origin using polymerase chain reaction amplification (PCR) of genomic DNA and oligonucleotide probes. We found a significant frequency increase of the alleles QAP 4.1 (RR = 10.3, p.c. = 10(-6) and QAP 2.1 (RR = 2.4, p.c. = 0.017) in patients over controls. An increased susceptibility is provided by the presence of both alleles, as is shown by the higher proportion of QAP 4.1, 2.1 heterozygotes among patients than expected from the Hardy-Weinberg equilibrium and by the comparison of the odds ratios for these alleles. There is a strong linkage disequilibrium between the QAP alleles and the DQA1, DQB1, and DRB1 loci. Two haplotypes carrying the QAP alleles whose frequency is increased are predominant in this group of CD patients: DQB1*0201, DQA1*0501, QAP4.1, DRB1*0301 and DQB1*0201, DQA1*0201, QAP 2.1, DRB1* 0701. Thus, the QAP variants are increased as part of these haplotypes and we cannot discriminate if they are responsible for the primary association.

[HLA antigens in patients with celiac disease]. / Výskyt HLA antigenu u nemocných s celiakií.

In 104 non-related children with coeliac disease, all from northern Moravia, the authors assessed the distribution of HLA antigens class I and II and compared the findings with a control group. They revealed a positive association between HLA A1 (62% sick subjects as compared 27% healthy ones), B8 (68% as compared with 18%), DR3 (66% as compared with 14%) and DQw2 (79% as compared with 23%). In HLA antigens class II there is a higher relative risk of the disease for subjects with antigens DR3 and DQw2 and a higher aetiological fraction for the investigated antigens.

[The importance of detection of antigliadin antibodies in the diagnosis and therapy of celiac disease in children]. / Význam vysetrení antigliadinových protilátek pro diagnostiku a lécbu celiakie u detí.

The authors describe the method of assessment of antigliadin antibodies class IgA and IgG by the ELISA method. In a group of children with untreated coeliac disease the antigliadin antibodies were elevated in 91.6%, in a group of children with coeliac disease after exposure to gluten in 87.8%, in children on a gluten-free regime in 48.5%. The dynamics of antigliadin antibodies in the course of the first year are presented--their decline in serum of children suffering from acute coeliac disease after elimination of gluten and conversely their rise after discontinuation of the gluten-free diet in children previously treated for prolonged periods. The sensitivity of the assessment is 91.6% and the specificity 90.6%.

[Clinical picture of Crohn's disease in children and adolescents]. / Klinický obraz Crohnovy nemoci u detí a dospívajících.

The authors describe the course of Crohn's disease in two boys and six girls aged 11.1-15.6 years. In three patients with terminal ileitis and affection of the ascendent colon the disease is characterized by prolonged growth retardation, subfebrile temperatures, abdominal pain. For patients with granulomatous colitis, blood-stained diarrhoea is typical abdominal pain and loss of body weight. Three patients were treated first for idiopathic proctocolitis and only in the course of the disease the diagnosis of Crohn's disease was established. In 87.5% of the patients on admission anaemia was found and all patients had a varying elevated red cell sedimentation rate and CRP. The author draws attention to extraintestinal symptoms (dermal, ophthalmological, articular, somatic retardation) which precede in particular somatic retardation) which precede in particular in affections of the small intestine intestinal manifestations. Their erroneous interpretation may delay the establishment of the diagnosis of Crohn's disease. The author emphasizes the importance of basic laboratory examinations and examination by ultrasound for early detection of patients.

Application of ELISA method to determine antigliadin antibodies in children with coeliac disease.

The application of the ELISA method to the detection of antigliadin antibodies (AGA), class IgG and IgA in children with coeliac disease (CD) is described. All the patients of the group of 17 with untreated CD and another group of 19 with CD formerly treated and now gluten exposed show elevated AGA values. The group of 14 CD patients permanently treated with gluten free diet show AGA increase in 42.6% cases. A correlation between the advanced grades of mucosal atrophy and pathological elevated AGA IgA values is found in this group. Patients with acute CD put on gluten free diet display a faster and more marked drop of AGA IgA than AGA IgG in the course of 3 to 12 months. Higher AGA values are found for children with inflammatory bowel diseases. The control group have higher AGA values in 6.45% of instances. Due to its sensitivity (100% by the assessment of both the AGA immunoglobulins) and 93.55% specificity AGA determination represents a valuable screening test both when indicating enterobioptic examination and following the gluten free diet of CD patients.