[Show abstract][Hide abstract] ABSTRACT: We studied the numbers of T-cell receptor alpha/beta- and gamma/delta-bearing lymphocytes in 27 jejunal specimens from 19 celiac patients, 27 rectal and colonic specimens from 14 ulcerative colitis patients and four patients with Crohn's disease, and 24 control specimens. MAb and a three-layer peroxidase staining method were used. Only low numbers of gamma/delta + cells were seen in normal jejunum and rectum of controls, as well as in the specimens of patients with inflammatory bowel diseases. In the lamina propria of celiac patients, the mean number of gamma/delta + cells was significantly higher than in the controls before treatment, during gluten-free diet, and after the gluten challenge. Within the jejunal epithelium, the number of gamma/delta + cells was elevated before and during gluten elimination and after the challenge test. The absolute number of intraepithelial gamma/delta + cells remained constant during gluten elimination and provocation. We infer that the constantly elevated population of gamma/delta + T cells in the epithelium of celiac patients may play an important role in the pathogenesis of celiac disease.
Pediatric Research 01/1991; 28(6):579-81. DOI:10.1203/00006450-199012000-00005 · 2.31 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The expression of HLA-DR by surface and crypt epithelium and the numbers of cells of natural killer (NK) phenotype and of IgE containing cells were studied with monoclonal antisera using the peroxidase technique. We examined 48 jejunal biopsy specimens taken from 35 coeliac children before treatment (11), during gluten free diet (20) and after gluten challenge (17), and 13 control specimens. The luminal surface of the epithelial cells stained with HLA-DR antiserum in all specimens, but the cytoplasm of the surface epithelial cells took up the stain more frequently in the specimens from the controls (5/13) than those from the coeliacs (2/48) (p less than 0.01). In 21/28 specimens taken from coeliacs when on a gluten containing diet the crypt epithelium showed strong HLA-DR expression, while only 4/20 (p less than 0.01) specimens of coeliacs on a gluten free diet and 1/13 specimens of controls had similar staining. Among the intraepithelial lymphocytes no cells of NK phenotype were found in specimens from patients or controls. As compared with control specimens biopsy specimens from untreated coeliac patients showed smaller numbers of NK cells in the lamina propria. No difference was found in the numbers of IgE containing cells between the patients and controls. The strong expression of HLA-DR by the crypt epithelial cells in coeliac children on a normal diet suggest that these cells are involved in the presentation of the antigen.
Gut 09/1987; 28(8):988-94. DOI:10.1136/gut.28.8.988 · 14.66 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The expression of HLA-DR by surface and crypt epithelium and the numbers of cells of NK phenotype and of IgE containing cells were studied with monoclonal antisera using the peroxidase technique in 48 jejunal biopsy specimens taken from 35 coeliac children and 13 control specimens. The surface epithelial cells stained with HLA-DR antiserum in all specimens. In 21/28 specimens taken from coeliacs when on a gluten containing diet the crypt epithelium showed strong HLA-DR expression, while only 4/20 /p<0,01/ specimens of coeliacs on a gluten free diet and 1/13 specimens of controls had similar staining. Among the intraepithelial lymphocytes no NK cells were found. No difference was found in the numbers of IgE containing cells between the patients and controls. The strong expression of HLA-DR by the crypt epithelial cells in coeliac children on a normal diet suggest that these cells are involved in the presentation of the antigen.
Pediatric Research 07/1987; 22(1). DOI:10.1203/00006450-198707000-00064 · 2.31 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A panel of monoclonal antibodies was used to determine the densities of T lymphocyte subsets in 48 jejunal biopsies of 35 children with coeliac disease (CD), 20 on gluten-free diet (GFD), 11 on normal diet and 17 on gluten challenge (GCh); and of 13 healthy controls. In lamina propria the age of the subject had a great influence on the T cell densities, with the numbers declining with age at a pace similar to that in peripheral blood in the control children. The correlation with the age was less obvious in CD patients. Among surface and crypt intraepithelial lymphocytes (IEL) the T suppressor cells predominated, and their numbers were significantly elevated on GCh as compared with CD patients on GFD, or the controls. The influence of the age on IEL T cell counts was negligible. A cell population bearing the “pan T” cell surface antigens but neither “T suppressor” nor “T helper” markers was identified within CD patients' IEL population, both on GFD and GCh. This cell population may be activated, and thus unable to express their cell surface antigens; or it may represent a unique cell population in the patients, relevant to the pathogenesis of coeliac disease.
Pediatric Research 07/1987; 22(1). DOI:10.1203/00006450-198707000-00065 · 2.31 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Twenty one children with dermatitis herpetiformis were studied in an attempt to evaluate the response in the skin, in jejunal morphology, and in jejunal immunoglobulin containing cell counts to gluten elimination and subsequent gluten challenge. In all of the 15 patients whose jejunal biopsy was studied after the eventual gluten challenge the jejunal lesion had returned in 2.4 to 28 months. The numbers of IgA- and IgM-containing cells were similarly raised in primary and postchallenge biopsies. In the 13 patients whose skin improved during a gluten free diet and who were challenged with gluten the rash worsened and the dapsone/sulphapyridine requirement increased. The jejunal deterioration was equally marked in the six patients whose gluten challenge was stopped because of an intractable rash as it was in those who completed the preplanned challenge. The specimens of the former, however, had significantly more IgA-containing cells than specimens of the latter. The number of intraepithelial lymphocytes clearly reflected the degree of intestinal damage. IgA-containing cells proved to be the most sensitive indicator of an immune reaction taking place in the gut of these patients. Even in the two children with initially normal or nearly normal jejunal mucosa, the IgA cell counts in the jejunal lamina propria were markedly raised.
Gut 01/1987; 27(12):1464-70. DOI:10.1136/gut.27.12.1464 · 14.66 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A case of coeliac disease where exceptionally long gluten challenge was needed to produce mucosal relapse is presented. An initial diagnosis of intestinal cow's milk allergy with total villous atrophy was made at the age of 3.5 months. The lesion healed after the child was put on a diet free of cow's milk and gluten. After 4.3 years on a normal diet his jejunal structure was still normal but at the age of 10.9 years, after 8.7 years of gluten ingestion, total villous atrophy was again observed. On a gluten-free diet the small intestinal structure is completely normal at the age of 17.1 years.
[Show abstract][Hide abstract] ABSTRACT: Forty-five Hungarian and Finnish children from 1.5 to 15 years with dermatitis herpetiformis were studied for HLA antigens, jejunal morphology on gluten-containing diet and associated diseases in the patients and their relatives. A strong association with HLA-B8 was found in patients of both nationalities, the relative risks were 12.8 and 9.6, respectively. The Hungarian patients were also typed for HLA-DR locus, and an association with DR3 but not with DR7 was observed. Patients with subtotal villous atrophy had slightly more often HLA-B8 and DR3 than those with milder intestinal lesions. Atopic eczema occurred in 20% of the patients and family history of atopy seemed to have an inverse correlation with HLA-B8 and DR3.
[Show abstract][Hide abstract] ABSTRACT: A case of abdominal wall fibrosarcoma in a 17-year-old girl with celiac disease and IgA deficiency is described. Celiac disease was putatively diagnosed with intestinal biopsy at the age of 15 years when she came for hospital investigations because of IgA deficiency and recurrent respiratory infections. The tumor occurred at the age of 17 years during the gluten challenge performed for final diagnosis of celiac disease. Surgical excision, irradiation, and chemotherapy were initially successful. After 7 months, however, the tumor recurred. Reoperation and a new course of irradiation therapy coinciding with the reinstitution of a gluten-free diet proved to be effective in tumor eradication. Nine years after the cessation of cancer treatment she is well and has two healthy children.
Journal of Pediatric Gastroenterology and Nutrition 11/1985; 4(5):839-41. DOI:10.1097/00005176-198510000-00028 · 2.63 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Cow's milk allergy (CMA) is multifaceted disease representing systemic, skin or gastrointestinal reactions to cow's milk (CM) protein. This article shortly reviews the intestinal form of CMA (ICMA). According us the child is allergic to CM when the immunologic reaction to CM is associated with clinical symptoms. The incidence of CMA is 1.3-1.9% in general, but the ICMA only 0.6 pro mille among the children less than six months of age. The majority of infants shows symptoms within a month of starting CM feeding. The majority of children with CMA have gastrointestinal symptoms. Manx of these infants has additionally dermatological symptoms and some respiratory symptoms. The mode of onset is often acute diarrhoea and vomiting, as in acute gastroenteritis. Laboratory findings indicate iron deficiency anemia in 20-70%. Half to two thirds of infants with chronic diarrhoea have moderate to severe steatorrhoea. The morphologic lesion in the gastrointestinal tract in ICMA is widespread, often being present from stomach to rectum. Jejunal lesion is most severe in the proximal part of the intestine and nowadays most patients have only partial villous atrophy or slight changes of the villi. Both the epithelium and the lamina propria of the jejunum are infiltrated with inflammatory cells. The morphology of the small intestine speaks for a strong immune reaction which leads increased destruction of surface epithelial cells. We recommend elimination of CM proteins to the age of 1.5 to 2 years. Most patients tolerate CM by the age of 2 years without symptoms. Prolonged breast-feeding and avoidance of early contact with CM are important in reducing the severity and frequency of CMA.
[Show abstract][Hide abstract] ABSTRACT: Coeliac disease is associated with the HLA Class I antigens A1 and B8 as well as with Class II antigens D/DR3, 7 and DC3. Class I antigens are important in the process of self recognition, guiding the cytolytic action of T killer cells, whereas Class II antigens are thought to regulate the functions of T helper and suppressor lymphocytes, and may be have a role in the intracellular transport of foreign macromolecules. Gliadin fractions were observed to adhere to the surface of B lymphocytes of patients with coeliac disease. The phenomenon was independent of the HLA antigen status (A, B, C, DR) of the patients, suggesting that the receptor for gliadin on the B cell surface is a yet unidentified B cell surface marker.
[Show abstract][Hide abstract] ABSTRACT: Feeding infants relatively safely with products derived from animal milk or vegetables has only been possible for about the past 100 years because this required clean water, the processing or at least diluting of foreign proteins, and even the invention of suitable vessels for infants to drink from. By the end of the last century, food derived from cow's milk had become the most popular form of infant feeding. However, at the beginning of this century some infants fed with cow's milk were found to have prolonged diarrhea, vomiting, and failure to thrive, which could be corrected only after the removal of cow's milk from their diet. 1 As early as 1910 these symptoms were considered a reaction to the foreign proteins in cow's milk and this was subsequently called cow's milk allergy (CMA). 2 Not before 1963, however, was it realized that CMA with intestinal symptoms was associated with morphologic changes in the jejunum. 3 In this paper we describe the morphologic changes in the intestinal tract in intestinal CMA (ICMA), the morphologic mechanisms that may cause such changes, and discuss why these mechanisms are activated in the diseased infant. We briefly describe the clinical symptoms and treatment of this disease.
[Show abstract][Hide abstract] ABSTRACT: HLA antigens and various aspects of atopy were studied in 42 Finnish children and adolescents with coeliac disease, and the results were compared with findings of recent population studies. The HLA associations were as expected: relative risks for coeliac disease in individuals with HLA-B8, DR3, and DR7 were 8 . 0, 18 . 6, and 15 . 0, respectively. Children with coeliac disease were significantly more often atopic than unselected schoolchildren. Atopy was significantly more frequent and the onset of coeliac disease later for B8/DR3- patients than B8/DR3+ patients. There was no obvious relation between DR7 and atopy. It is concluded that atopy predisposes to coeliac disease partly independently of the HLA-DR3 associated disease susceptibility gene(s), and that different mechanisms may operate in the pathogenesis in coeliac disease patients with and without atopy.
Gut 05/1983; 24(4):306-10. DOI:10.1136/gut.24.4.306 · 14.66 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The histocompatibility antigens of one hundred patients with a severe form of cow's milk allergy were studied. HLA-A and B locus antigens were identified in all patients, C locus antigens in 62 patients and DR locus antigens in 41 patients. The A, B and C locus antigen frequencies were compared with those of healthy blood donors, and DR locus antigen frequencies with those of healthy unrelated volunteers and cadaver kidney donors. The series included six patients with concomitant coeliac disease, who were treated as a separate group. No statistically significant differences between the patients and controls were observed, but suggestive differences became apparent when the patient group was divided into subgroups according to the presence or absence of certain co-existing conditions, and the severity of the initially observed intestinal lesion. It is concluded that several factors contribute to the pathogenesis of intestinal cow's milk allergy, and that in some cases genes linked to the HLA region may play a role.
[Show abstract][Hide abstract] ABSTRACT: The rapid changeover to commercial adapted infant formulae which took place in Finland between 1973 and 1975 was studied as a factor in the occurrence of severe intestinal cow's milk intolerance (CMI). Of infants treated for CMI in 1962-73, ninety-three percent (25/27) were on homemade or unadapted formulae. The admission rate for CMI in these years was 0.22/1 000 liveborn infants breast fed less than six months. During 1974-77 the corresponding figure was 0.56, with 85% of the patients (18/26) on adapted cow's milk formulae. The patients treated before 1974 had a longer symptomatic period before admission, greater growth retardation and more severe intestinal damage than those seen during and after 1974. This is believed to reflect mainly the increasing awareness of CMI on the part of both laymen and the medical profession. In the history of 2/3 of the patients at least one of the following conditions was noted: non-breast feeding, infectious gastroenteritis, praematurity, 21-trisomy, prior intra-abdominal surgery, Hirschsprung's disease, and atopic disease in family members. The long follow-up averaging over four years revealed four patients with coeliac disease. In one of these the proximal jejunal mucosa was normal after two years on gluten-containing diet, but he showed a mucosal relapse as late as between 2 to 4 years on normal diet.
[Show abstract][Hide abstract] ABSTRACT: In 14 children and adolescents, abnormally short stature was shown to be due to celiac disease (CD) though the patients had no current gastrointestinal symptoms. Growth failure had appeared in the first years of life, and was associated with a marked lag in bone age. Subnormal growth hormone (GH) responses were demonstrated in 4 patients, and subnormal ACTH responses in 2. In 1 patient permanent isolated GH deficiency coincided with CD. A jejunal biopsy should form part of the routine diagnostic evaluation for abnormally short stature, except in patients who have had normal growth during the first year of life.
[Show abstract][Hide abstract] ABSTRACT: Among subjects investigated for growth failure we have seen ten, who had no subjective gastrointestinal symptoms, but who were demonstrated to have coeli ac disease. They were 4–19 years of age, and 2–7 S.D. below the height expected for their age and parental heights. In five cases, a history was obtained of a period of diarrhoea in infancy. Five had had an anaemia refractory to iron therapy. Eight had some protuberance of the abdomen. The bone age was markedly lagging in all, by 3–7 years. No consistent chemical abnormality was found: blood hemoglobin and folate, serum iron and TIBC, and fecal fat excretion were abnormal in only 4–5 of the subjects, and all these parameters were normal in two. Three had a subnormal growth hormone response to insulin-arginine test, one of them repeatedly. The diagnosis was based on the demonstration of a flat jejunal mucosa by peroral biopsy. In five, the diagnosis has been confirmed by a significant acceleration of growth after institution of a glutein-free diet. We presently include jejunal biopsy in the routine evaluation for abnormally short stature.
Pediatric Research 08/1975; 9(8). DOI:10.1203/00006450-197508000-00049 · 2.31 Impact Factor