Celiac disease in Turkish children: Presentation of 104 cases

BACKGROUND: Celiac disease is characterized by life-long gluten intolerance. Clinical features of patients with celiac disease are variable. In the present study, clinical, laboratory and histologic features of 104 patients with celiac disease were evaluated. METHODS: Intestinal biopsy and serum antigliadin and anti-endomysium antibodies were used for the diagnosis of patients. Mucosal lesions were classified according to the criteria of Marsh. Antigliadin antibodies were measured with a commercial enzyme-linked immunosorbent assay. Anti-endomysium antibodies were analyzed by indirect immunofluorescence with the use of a section of monkey esophagus. Routine hematological and biochemical analyses and measurement of immunoglobulin levels were undertaken. RESULTS: The mean (+/- SD) patient age was 5.9 +/- 4.1 years (range 10 months-16 years) and the most common symptom was diarrhea (81.7%) followed by abdominal distention, weight loss, anorexia and failure to thrive. Abdominal distention (60.6%), short stature (45.2%) and iron-deficiency anemia were the most common findings. High serum alanine aminotransferase levels were found in 38.3% of patients and these levels became normal after adoption of a gluten-free diet in all but two patients with cirrhosis. Immunoglobulin A, IgG antigliadin antibodies and IgA anti-endomysium antibodies were found in 76, 94 and 90% of patients, respectively. Biopsy of the small intestine revealed that 95, two and seven patients had type 3, type 2, and type 1 lesions, respectively, according to the Marsh classification. There was no statistically significant difference between patients and control groups with regard to antinuclear antibody, antismooth muscle antibody, anti-DNA and anticardiolipin antibodies (IgG and IgM). CONCLUSIONS: Although classical celiac disease was seen in most patients in the present study, clinical variability of the condition should be kept in mind. In particular, patients with uncommon findings, such as short stature, cryptogenic liver disease and iron-deficiency anemia, should also be screened for celiac disease.     

Quality of life in children with diabetes and celiac disease: minimal impact of the 'double diagnosis'

Sud S, Marcon M, Assor E, Daneman D and Mahmud FH. Quality of life in children with diabetes and celiac disease: minimal impact of the ‘double diagnosis'. Background: Despite the advent of sensitive testing to detect celiac disease (CD), screening in type 1 diabetes (T1D) remains controversial. Many diabetes clinics are apprehensive about the prospect of introducing a second illness requiring intensive lifestyle changes in patients and families already managing a chronic condition, especially in asymptomatic patients. Objective: To determine the impact of managing CD + T1D on quality of life in families, with attention to the effect of adherence with a gluten‐free diet (GFD) and metabolic control. Patients and Methods: Cross‐sectional assessment using a validated self‐reported quality of life measure: 28 children with biopsy‐proven CD + T1D were compared with 40 subjects with T1D aged 8–18 yr. Parental and child reports were assessed as well as symptoms at the time of CD diagnosis and adherence with a GFD at the quality of life assessment. Results: No significant differences in quality of life were observed between subjects with established CD + T1D and subjects with T1D alone. Parents of children with CD + T1D reported lower social functioning scores than parents of children with T1D (p = 0.03). In the CD + T1D group no differences in quality of life were observed with regard to age at CD diagnosis, CD duration, or on the basis of adherence with a GFD. Conclusions: The additional diagnosis of CD has minimal impact on quality of life in children with T1D; however, parents of CD + T1D children did express greater concern about their child's social functioning.     

Human leukocyte antigens in Turkish pediatric celiac patients

With the aim to determine the frequency of human leukocyte antigen phenotypes of celiac disease in Turkey, thirty celiac patients fulfilling the European Society of Pediatric Gastroenterology and Nutrition criteria were included in the study. The mean age of the study population was 5.8 +/- 4.3 years and of the control subjects was 32.6 +/- 6.7 years. The human leukocyte antigens -A, -B, -DR and -DQ were studied serologically by micro lymphocytotoxic reaction. It was found that human leukocyte antigens A-25(10), -B8, -DR18(3) and -DQ2 were more significantly frequent in the celiac population than in the control group. Children with antigen -B8 showed a five times higher risk for celiac disease and those with antigen -DQ2 showed a nine times higher risk. It was determined that human leukocyte antigen -B4 had a protective role in celiac disease. The study suggests that the human leukocyte antigen -A25(10) is a phenotype particularly encountered in Turkish pediatric celiac patients.     

Allogeneic stem cell transplantation in children with leukemia using human leukocyte antigen-mismatched unrelated donors

Allogeneic HSCT is a curative treatment, when chemotherapy fails, for certain malignant diseases. In Europe, only 15% of the indicated children have an HLA-matched sibling available; in 65-70% of others, HLA allele-matched (9-10/10) UDs can be identified. For the rest, it is necessary to identify other alternative donors (HLA-mismatched family or unrelated cord blood). We present our data of HSCT using HLA partially allele-mismatched (7-8/10) UDs in 24 children with leukemia. Uniform GvHD prophylaxis was used (rATG, CsA and MTX). Acute GvHD grade II was diagnosed in 70.8% of the patients and grade III-IV in 12.5%. Overall incidence of chronic GvHD was 38.7% (extensive in 30%). The probability of EFS was 60.3% (95% CI 35.5-78.1) and OS was 74.9 (95% CI 49.1-88.9). No difference in survival between PBSC and BM recipients was observed. TRM at day + 100 was 4%, and overall was 12.5%. We conclude that used combination of drugs for GvHD prophylaxis is efficient even for patients transplanted with grafts from a HLA-mismatched UDs. It enables stable engraftment, good control of GvHD, full reconstitution of immunity, and is not connected with unacceptable transplant-related mortality.     

Endomysium antibodies in the diagnosis of celiac disease in short-statured children with no gastrointestinal symptoms

BACKGROUND: Endomysium antibodies (EmAb) are strongly associated with untreated celiac disease and are suggested to be diagnostic. The aim of the present study was to assess the value of anti-EmAb for celiac disease screening in children with short stature. METHODS: In 84 children with height less than the third percentile for age, preliminary work-ups were made to find a cause for their short stature and then their serum was assayed for anti-EmAb by indirect immunofluorescence tests using monkey esophagus. RESULTS: Seven children were strongly positive for EmAb and all had positive histologic findings for celiac disease. CONCLUSIONS: Our results show that there is an association with occult celiac disease and idiopathic short stature and that the serum anti-EmAb test is useful in identifying such cases.     

Elevated levels of serum antibodies to the lectin wheat germ agglutinin in celiac children lend support to the gluten-lectin theory of celiac disease

Lectins recognize carbohydrate moities of glycoproteins and glycolipids, and can elicit several biological effects, including cell agglutination, cell activation and mitogenesis. According to the gluten-lectin theory, celiac lesions represent a response to a toxic lectin, putatively wheat germ agglutinin (WGA). In this study we compared the serum antibody levels IgA, IgG and IgM to WGA and to gliadin in children under investigation for celiac disease (CD), as compared to reference children. We found that the levels of IgA and IgG to WGA as well as gliadin were significantly higher in celiac children on a gluten-containing diet, compared to children on gluten-free diet and reference children. These findings lend support to the concept that WGA is a biologically significant component of gluten. Since WGA can mimic the effects of epidermal growth factor (EGF) at the cellular level, we hypothezise that the crypt hyperplasia seen in celiac children could be due to a mitogenic response induced by WGA.     

Uptake of antigens: Role in gastrointestinal disease

The intestine is exposed to a wide variety of macromolecules. Because macromolecules are antigenic, mechanisms have evolved in the gastrointestinal tract to regulate their absorption. Macromolecular uptake can be beneficial in delivering essential factors for growth and in sampling the antigenic milieu of the gastrointestinal tract. Specific transport mechanisms exist to execute this physiological absorption. However, inappropriate and uncontrolled antigen transport may occur in disease states, or as a prelude to disease states in the gastrointestinal tract. Such transport may result in immune responses that are harmful. In this review we examine both physiological transport of macromolecules through epithelia and through M cells. We also discuss uncontrolled transport and its relation to disease states. We conclude by examining the interrelationship between antigen transport and an altered immune system in the establishment of gastrointestinal disease.     

Lack of association between childhood stroke after varicella and human leukocyte antigen (HLA)-B51

Human leukocyte antigen (HLA)-B51 has been suggested as an immunogenetic marker for a genetic predisposition to vascular occlusion in response to an immunological stimulus. Varicella has been reported to be a possible risk factor for stroke. We performed DNA-based HLA typing in 11 young patients (mean age: 5.2 years) with unexplained ischaemic stroke. In eight of them varicella had occurred before their stroke. HLA-B51 was negative in all 11 patients and we did not find any significant accumulation of other HLA-subgroups. Our study does not support an association between susceptibility to stroke after varicella and HLA-B51.     

Plasma cytokine profiles in patients with celiac disease and selective IgA deficiency

Celiac disease (CD) and selective IgA deficiency (IgAD) are frequently associated, and share the same genetic background. The aim of the present study was to evaluate both Type 1 and 2 plasma cytokine levels in CD and in CD-IgAD. IL-2, TNF-α, IL-10, IL-4 and IL-13 plasma levels were measured both at diagnosis and after a gluten-free diet (GFD) in 32 CD patients, in 27 CD-IgAD patients and in 30 healthy controls. IFN-γ levels were significantly higher in CD and CD-IgAD than in controls, TNF-α displayed significantly higher levels in CD-IgAD when compared both with controls and with CD, and IL-2 was in CD-IgAD significantly increased respect to controls. Kinetics of the Type 1 cytokine plasma levels did not show a clear relationship with the GFD in both groups of CD patients, and particularly in those with IgAD. IL-4 and IL-13, both at diagnosis and after a GFD, were not significantly different in controls and in celiac patients (with and without IgAD). IL-10, whose production is stimulated by the TNF-α, had significantly higher plasma levels in CD-IgAD, but not in CD patients, with a significant decrease after a GFD. CD and especially CD-IgAD patients display persistently higher pro-inflammatory cytokine levels, suggesting a persistent state of activation of pro-phlogistic signals in CD, particularly when IgAD coexists. Serial measurement of serum IL-10 may be an adjunctive evaluating criterion in the follow-up of CD-IgAD patients.     

Infant feeding history shows distinct differences between Swedish celiac and reference children

Infant feeding history was investigated in 72 celiac and 288 age-matched reference children in a retrospective questionnaire study. The reply rate was 100% in celiac and 91. 6% in reference children. The celiac children were breast-fed for a significantly shorter time than reference children, and they were less often breast-fed at the introduction of gluten. The age of the children at gluten introduction was similar, but the cellac children were significantly more often introduced by a gluten-containing follow-up formula, while the reference children more often started on a gluten-containing porridge. The results can be interpreted in two ways. First, it could be argued that breast milk per se protects against symptoms of celiac disease in childhood. It could, however, also be claimed that breast-feeding merely modulates the gluten introduction, causing a less abrupt introduction of gluten in the baby diet and thereby fewer overt symptoms of the disease.     

Polymorphisms of the TNF-alpha gene and risk of celiac disease in T1DM children

BACKGROUND: Type 1 diabetes mellitus (T1DM) and celiac disease (CD) frequently occur together. Previous reports suggested that the (-308)A variant of the tumor necrosis factor-alpha (TNF-alpha) gene is associated either with T1DM or with CD. The aim of our study was to determine whether (-308)A and (-238)A allelic variants of the TNF-alpha gene might have any impact on the risk of CD in T1DM children. METHODS: Three hundred and one T1DM children were enrolled to the study. The presence of CD was screened with IgA endomysial antibodies (EMA) test. Jejunal biopsy was performed to confirm CD. TNF-alpha-308 and -238 genetic variants were tested using the method of restriction fragment length polymorphism. RESULTS: The prevalence of CD in the enrolled diabetic children was 6.3% (19 out of 301 children). The frequency of the (-308)A TNF-alpha variant was similar in the CD and the non-CD groups, exceeding the Hungarian healthy reference value. The number of (-238)A allele carriers was higher in the CD (4/19) than in the non-CD group (17/277) (p < 0.05). CONCLUSIONS: Our study is limited by the small number of CD patients. On the basis of our findings, carriers of TNF (-308)A allele do not seem to have an increased risk for CD in T1DM. The association between TNF-alpha(-238)A allele carrier state and CD requires further investigation.