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[Serum antigliadin antibodies in the diagnosis and follow-up of celiac disease].

Between July 1985 and June 1990, we prospectively investigated 236 children suspected of having malabsorption syndrome. Each patient had a xylose absorption test and small intestinal biopsy. Blood samples were collected to AGA assay. The aim of the study was to evaluate the use of antigliadin antibodies test, IgG and IgA, in screening celiac disease for intestinal biopsy and in the monitoring of gluten-free diet and challenge in celiac patients. Twenty patients were diagnosed with celiac disease confirmed by three small intestinal biopsies; 12 patients were suspected of having celiac disease, with two biopsies, before and one year after a gluten-free diet; 106 patients had environmental enteropathy; 45 patients had protracted diarrhea and 56 children had failure to thrive with no gastrointestinal symptoms. The AGA test was considered a reliable test in screening for biopsy and in the differential diagnosis between celiac disease and other causes of malabsorption syndrome. The IgG AGA test had high sensitivity (90.4%) and the IgA AGA test had high specificity (92.1%) in screening for celiac disease. In the follow-up of the celiac patients the antibody levels were significantly higher during gluten containing diet than after gluten avoidance being thus a reliable test to evaluate dietary compliance.

Autoantibodies↗

Elevated IgD antibodies to wheat in celiac disease.

Sera of 17 patients with gluten-induced celiac disease were studied. Total serum IgE and IgD, as well as specific IgE and IgD antibodies to selected food antigens, were determined. Total IgE levels were within the normal range. Specific IgE antibodies to wheat, alpha-gliadin, cows's milk, rice and buckwheat were comparable to those of normal controls. In the celiac subjects total IgD levels were also within the normal range but IgD antibodies to wheat were high whereas IgD antibodies to milk were lower than in pooled normal sera. The levels of IgE or IgD antibodies to either wheat or milk showed no relationship to the presence of precipitins to the antigens of these two foods. The study did not demonstrate a role for IgE in celiac disease. That IgD antibodies may play a role is suggested by the elevated serum IgD antibodies to wheat antigens.

Adolescent↗

Limited efficiency of prolyl-endopeptidase in the detoxification of gliadin peptides in celiac disease.

BACKGROUND & AIMS: The resistance of prolamines to digestive enzymes is thought to be a key contributor to the pathogenesis of celiac disease by promoting the intestinal entrance of peptides able to trigger inflammation in at-risk individuals. Oral administration of a bacterial prolyl-endopeptidase (PEP) therefore was proposed as a treatment for celiac disease. To delineate the feasibility of this treatment, the effect of PEP on gliadin peptides was assessed in vitro, and ex vivo during their transport across intestinal biopsy specimens of active celiac disease patients. METHODS: In vitro degradation by PEP of 3H-labeled gliadin peptides 56-88 (33-mer) and 31-49, was analyzed by radio-reverse-phase high-performance liquid chromatography and mass spectrometry. For ex vivo studies, PEP and 3H-peptides were added together onto the mucosal side of duodenal biopsy specimens mounted in Ussing chambers, and peptide transport and digestion were assessed by radio-reverse-phase high-performance liquid chromatography. RESULTS: Gliadin peptides were degraded partly by 20 mU/mL PEP both in vitro and ex vivo. This concentration of PEP decreased the amount of intact peptides 31-49 and 56-88 crossing the intestinal biopsy specimens of celiac disease patients, but could not prevent the intestinal passage of toxic or immunostimulatory metabolites. PEP concentrations of at least 500 mU/mL for 3 hours were required to achieve full detoxification of peptides and to prevent intestinal transport of active fragments. CONCLUSIONS: After prolonged exposure to high concentrations of PEP, the amount of immunostimulatory gliadin peptides reaching the local immune system in celiac patients is decreased. These results provide a basis to establish whether such conditions are achievable in vivo.

Biopsy↗

Psychological dimensions of celiac disease: toward an integrated approach.

Psychic alterations have been reported in celiac disease. Our aim was to evaluate the emotional impact of celiac disease diagnosis in adulthood, the patient/doctor relationship, and the patients' cooperation with disease treatment and diet. The patients were 114 adult celiac patients on a gluten-free diet, there were 25 untreated celiac patients. Self-administered questionnaires aimed to evaluate the patients' level of knowledge of disease, the emotional impact at diagnosis, and feelings during follow-up. Celiac patients showed good knowledge of the disease, directly correlated to their socioeconomic level (P = 0.011). At diagnosis, relief was most intense feeling (Mean +/- SD, 10.82 +/- 7.63), demographics, time latency of diagnosis, and the duration of the disease had no effect on the intensity of all feelings. The scores of the self-rated emotions were entered into a principal component analysis that generated three factors: 1 (fear, anger, anxiety and sadness), 2 (reassurance and resignation), and 3 (relief); patients judged the clinicians presenting the disease "in the right way" (F = 33.279; P < 0.0001). The right way correlated with relief and reassurance (P = 0.0009; P = 0.0008 respectively). At follow-up, anger was the predominant emotion that induced patients to transgress. A positive correlation was observed between feeling different and the sadness, anger, fear (P < 0.0001 for all). Anger was inversely correlated with actual compliance to diet (P = 0.0005). In conclusion, in adult patients, adaptive and psychological aspects must be taken into account to understand the celiac patient and for better clinical management.

Adaptation, Psychological↗

Toxicity mechanisms of wheat and other cereals in celiac disease and related enteropathies.

This paper is a critical appraisal of current theories on the mechanisms of toxicity of wheat and other cereals in celiac disease and some related enteropathies. The "peptidase deficiency," "primary immune defect," and "gluten-lectin" theories on celiac disease are examined and critically discussed on the basis of the relevant data available in 88 references. Special attention has been paid in this review to the nature of the cereal components triggering the appearance of toxic symptoms and signs in celiac disease as well as to underlying action mechanisms. The gluten-lectin theory is the one best able to explain, in addition to celiac disease, some secondary intolerances that may occur in temporarily predisposed individuals as a consequence of several causes, including viral hepatitis and intestinal infections, as well as the occurrence of intestinal lesions in healthy subjects administered very high amounts of gluten.

Animals↗

The diagnostic value of the gliadin antibody test in celiac disease in children: a prospective study.

Serum gliadin antibodies (IgA/IgG) were determined in 191 consecutive children (median age, 2.75 years; range, 0.33-15.5 years) admitted for a small-intestinal biopsy on suspicion of celiac disease. The test was a diffusion-in-gel enzyme-linked immunosorbent assay (DIG-ELISA). Of these 191, 14 (7.3%) appeared to have untreated celiac disease. Depending on the choice of cut-off value of the test (combined determination of IgA and IgG), the sensitivity was 86-100%, the specificity was 97-99%, and the positive/negative predictive values were 70-92% and 99-100%, respectively. No variation according to age was found. Gliadin antibodies were determined in 47 children who had well-treated celiac disease. Fourteen of these children were also investigated when challenged with gluten. Gliadin antibodies (IgA or IgG) decreased significantly in 13 of 13 cases when the patients shifted from a gluten-containing diet to a gluten-free one. During the gluten challenge, the IgG and IgA increased in 14 of 14 and 11 of 14 cases, respectively (two patients suffered from IgA deficiency). In eight patients who later appeared to be free of celiac disease, the gliadin antibodies were determined on gluten-free diet and during gluten challenge; no significant differences in gliadin antibodies were found. We conclude that this test is useful in selecting patients with symptoms suggesting celiac disease for a small-intestinal biopsy. The test seems to be of some value in monitoring the effects of a gluten-free diet and during gluten challenge.

Adolescent↗

Reversible inflammatory and vacuolar myopathy with vitamin E deficiency in celiac disease.

We report a patient with late-onset celiac disease and neurological manifestations including myopathy, polyneuropathy, and ataxia. Laboratory investigations showed anti-gliadin antibodies and severe vitamin E deficiency. Muscle biopsy revealed inflammatory infiltrates and rimmed vacuoles, similar to those found in inclusion-body myositis. A gluten-free diet and vitamin E supplementation reversed both the clinical neurological manifestations and the abnormalities in the muscle biopsy. Anti-gliadin antibodies were no longer present. This case illustrates the spectrum of neurological complications of celiac disease and documents the occurrence of reversible pathology resembling inclusion-body myopathy in the muscle.

Aged↗

Immunoglobulin levels in children with celiac disease: variations with age and diet.

Serum immunoglobulins were evaluated in 110 children with celiac disease ranging in age from three months to 15 years. IgG, IgM and IgA were evaluated in all the patients when they were on either a normal or a gluten-free diet and the findings were analyzed by age and type of diet. IgG and IgM levels were generally higher than normal. The type of diet did not affect the results. IgA levels were higher in untreated (normal diet) than in treated (gluten-free diet) celiac patients or normal subjects. The IgA levels returned to normal when the patients were on a gluten-free diet. The variations in immunoglobulin levels among the different age groups of celiac patients reflect the normal variations in serum immunoglobulins with age. It is suggested that the higher IgA levels in untreated celiac disease patients are evidence of chronic stimulation of the B cell immune system and that this could be a factor in the high incidence of lymphoreticular abnormalities and malignant tumors in adults with celiac disease.

Adolescent↗

Effect of treatment on bone mass, mineral metabolism, and body composition in untreated celiac disease patients.

BACKGROUND/AIMS: Osteopenia is a common complication of celiac disease. The aims of this study were to evaluate whether treatment produces bone remineralization and whether calcium and vitamin D supplementation are necessary to reduce osteopenia. METHODS: Bone mineral density and biochemical parameters of bone and mineral metabolism were measured in 14 newly diagnosed adult celiac disease patients. All patients were treated with a gluten-free diet and were randomized to receive diet only (n = 7) or diet plus calcium (1.0 g/day) and vitamin D (32,000 IU/wk) supplementation (n = 7). Bone density was measured at baseline and at 6 and 12 months of follow-up. Tests for biochemical determinations were repeated every 3 months. RESULTS: At diagnosis, 11 patients had evidence of osteopenia (> 1 SD below normality) in the spine and total skeleton. After 12 months of gluten restriction, overall bone mass had increased 5.0% (p < 0.01) in the lumbar spine and 5.0% (p < 0.002) in the total skeleton. When one only considers those 11 patients who strictly followed gluten restriction, bone density increased 8.4% in the lumbar spine and 7.7% in the total skeleton. Remineralization occurred throughout the skeleton but was more pronounced in the axial than in the peripheral skeleton. The increase in bone mass was independent of age or menopause. Remineralization in patients treated with diet only was similar to that of patients treated with diet and supplements. Basal biochemical parameters showed a high bone turnover with secondary hyperparathyroidism. Treatment induced a decrease in bone turnover activity. However, a complete restoration of biochemical parameters was not achieved. CONCLUSIONS: Strict gluten avoidance promoted a significant increase in bone mineral density. However, values still remain markedly low after 1 yr in several patients. Although calcium and vitamin D supplementation did not provide additional benefit to that obtained by diet alone in the doses administered, our results do not preclude a possible effect of vitamin D at higher dose.

Adult↗

[Prevalence of undiagnosed celiac disease in patients with irritated bowel syndrome].

In the article insufficiency of existing patterns of investigation of patients with irritated bowel syndrome (IBS) during differential diagnostics with celiac disease is underlined, that leads to wrong diagnostics and inefficient treatment of patients. Also own data on prevalence of celiac disease in patients with IBS are shown. Determination of the level of specific markers of celiac disease (in our research--antigliadin Ig) is considered to be the optimal method of diagnostic celiac disease in this group of patients.

Adolescent↗

Increased HLA-DR expression by enterocytes in children with celiac disease.

Class II histocompatibility antigens, known to be present on immunocompetent cells, were recently demonstrated on enterocytes. Because of their role in antigen presentation and immune response regulation, HLA-DR antigens were studied in patients with celiac disease. Cryostat sections of jejunal biopsy specimens were stained with several anti-DR monoclonal antibodies using an avidin-biotin peroxidase technique. Thirty patients with celiac disease either active (n = 5), in remission (n = 10), or in relapse (n = 15) were compared with 16 controls, 9 with a normal mucosa and 7 with a flat mucosa but without celiac disease. In celiac patients with active disease or in relapse, enterocytes were heavily stained on the surface epithelium and the crypts. This contrasted with the absence of crypt staining in the biopsy specimens of the other patients. Increase in DR expression was associated with an increase in the number of T8(+) lymphocytes in the crypts. Modulation of DR expression by enterocytes may be involved in the pathogenesis of celiac disease.

Adolescent↗

Celiac disease and the spectrum of gluten sensitivity.

Celiac disease is a well-known entity in which intolerance to wheat gluten and related proteins from barley, rye, and oats (collectively known as prolamins) damage intestinal mucosa. New insights into the pathology of the celiac intestinal lesion point to a wider spectrum of gluten sensitivity than previously thought. Recent advances in immunology and genetics have shed light on the underlying mechanisms and risks associated with the disease. Although the classical manifestations are well known, the wide variety of clinical presentations make celiac disease often difficult to diagnose, and the ubiquitous presence of prolamins in the Western diet make treatment challenging.

Celiac Disease↗

Human CD8+ intraepithelial T lymphocytes are mainly CD45RA-RB+ and show increased co-expression of CD45R0 in celiac disease.

Expression of various CD45 isoforms (RA, RB and R0) on CD3+, CD4+ and CD8+ intraepithelial and lamina propria T cells was examined in situ by a three-color immunofluorescence technique in jejunal biopsy specimens from 32 patients with celiac disease and 18 controls. The median percentage of CD3+ intraepithelial lymphocytes (IEL) that expressed CD45R0 increased from 52% in controls to 69% in untreated celiac disease (p less than 0.01). Furthermore, the percentages of CD4+ and CD8+ IEL strongly positive for CD45R0 rose respectively from 94% and 24% in controls to 100% and 55% in untreated celiac disease. Conversely, CD45R0 was strongly expressed on most CD3+ lamina propria lymphocytes (LPL) both in control (81%) and diseased (77%-81%) mucosa. A variable fraction of the intraepithelial and lamina propria CD3+ T cells expressed mainly CD45RB (controls, 46% and 20%, respectively; celiac disease, 29% and 15%). Only 2% IEL and 4% LPL were positive for CD45RA. Expression of different CD45R isoforms thus identified three distinct CD8+ T cell subsets in human intestinal mucosa. In addition, our results suggested that antigen-primed CD8+CD45R0+ memory cells accumulate in the jejunal epithelium of patients with untreated celiac disease.

Adolescent↗

Small intestinal T cells of celiac disease patients recognize a natural pepsin fragment of gliadin.

Celiac disease is a common severe intestinal disease resulting from intolerance to dietary wheat gluten and related proteins. The large majority of patients expresses the HLA-DQ2 and/or DQ8 molecules, and gluten-specific HLA-DQ-restricted T cells have been found at the site of the lesion in the gut. The nature of peptides that are recognized by such T cells, however, has been unclear so far. We now report the identification of a gliadin-derived epitope that dominantly is recognized by intestinal gluten-specific HLA-DQ8-restricted T cells. The characterization of such epitopes is a key step toward the development of strategies to interfere in mechanisms involved in the pathogenesis of celiac disease.

Amino Acid Sequence↗

Catch-up growth and endocrine changes in childhood celiac disease. Endocrine changes during catch-up growth.

Childhood celiac disease may lead to a failure of statural growth. After institution of a gluten-free diet most patients exhibit catch-up growth. Catch-up growth is a remarkable phenomenon characterized by a supranormal height velocity. One of the hypothetical mechanisms of catch-up growth is that an increased activity of the somatotrophic axis is involved. In order to provide further insight in the physiology of catch-up growth, auxological and endocrine changes were prospectively studied in 28 children with newly diagnosed celiac disease. The results demonstrate a malnutrition-like state of the somatotrophic axis at the time of diagnosis and a rapid recovery of this axis towards normal functioning after institution of the gluten-free diet. Although several correlations between these endocrine alterations and auxological parameters were detected, it is questionable whether the endocrine changes are the driving force behind catch-up growth.

Body Height↗

Celiac disease and pregnancy outcome.

OBJECTIVES: This study investigated the effect of gluten-free diet on pregnancy outcome and lactation in 125 women affected with celiac disease. METHODS: The study has been designed as a case-control study and a before-after study. RESULTS: In the case-control study, comparison of 94 untreated with 31 treated celiac women indicated that the relative risk of abortion was 8.90 times higher (95% confidence limits: 1.19/66.3), the relative risk of low birth weight baby was 5.84 times higher (90% confidence limits: 1.07/31.9), and duration of breast feeding was 2.54 times shorter (p < 0.001) in untreated mothers. Abortion, low birth weight of baby, and duration of breast feeding did not significantly relate to the severity of celiac disease among untreated women. In the before-after study, 12 pregnant celiac women in either treated or untreated condition were compared. Results indicated that the gluten-free diet reduced the relative risk of abortion by 9.18 times (95% confidence limits: 1.05/79.9), reduced the number of low birth weight babies from 29.4% down to zero (p < 0.05), and increased duration of breast feeding 2.38 times (p < 0.10). Both case-control and before-after studies indicated that threatened abortion and premature delivery did not significantly relate to treatment of celiac disease. CONCLUSIONS: The high incidence of abortion, of low birth weight babies, and of short breast-feeding periods is effectively corrected by gluten-free diet in women with celiac disease.

Abortion, Spontaneous↗

Celiac disease onset after pegylated interferon and ribavirin treatment of chronic hepatitis C.

AIM: Report of a case of a woman patient who developed celiac disease after pegylated interferon alpha-2a and ribavirin use for chronic hepatitis C. PATIENT AND METHOD: A 34-year-old woman with chronic hepatitis C, genotype 3, receiving pegylated interferon alpha-2a and ribavirin for 6 months, developed progressive malaise and anemia 6 months after the end of treatment. RESULT: Additional investigation revealed duodenal villous atrophy and positivity for anti-endomysium and anti-gliadin antibodies. Celiac disease diagnosis was performed and symptoms and laboratory abnormalities improved after gluten-free diet. CONCLUSION: Celiac disease must be ruled out in patients with malabsorption complaints in or after interferon (or pegylated interferon) therapy. Screening for celiac disease with detection of anti-endomysium antibodies would be done in susceptible patients.

Adult↗

Histologic follow-up of people with celiac disease on a gluten-free diet: slow and incomplete recovery.

To assess histologic recovery in response to gluten withdrawal in celiac disease, 158 patients seen in our hospital during a 15-year period underwent follow-up small intestine biopsies (SIBs) within 2 years after starting a gluten-free diet; further SIBs were done if villous atrophy was present. A modified Marsh classification was used (IIIA, partial villous atrophy; IIIB, subtotal villous atrophy; IIIC, total villous atrophy). Of patients with Marsh IIIA, IIIB, or IIIC lesions, histologic remission was seen in 65.0% within 2 years, 85.3% within 5 years, and 89.9% in long-term follow-up. Eleven patients (7.0%) with persisting (partial) villous atrophy had symptoms and signs of malabsorption and were considered to have refractory celiac disease; 5 of them developed an enteropathy-associated T-cell lymphoma. Children recovered up to 95% within 2 years and 100% in the long-term. Histologic recovery in celiac disease after starting a gluten-free diet takes time and is incomplete or absent in a substantial subgroup of patients (10.1% villous atrophy after 5 years). Systematic follow-up of patients with celiac disease and the malabsorption syndrome and secondary complications is needed.

Adolescent↗