Intestinal gamma/delta receptor-bearing T lymphocytes in celiac disease and inflammatory bowel diseases in children. Constant increase in celiac disease

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.     

Diminished concentrations of insulin-like growth factor I in cystic fibrosis

Cystic fibrosis is frequently accompanied by a catabolic condition with low body mass index caused by a number of disease complications. Insulin-like growth factor-I (IGF-I) is an anabolic hormone and an important marker of nutritional status, liver function, and linear growth. Available data on IGF-I in cystic fibrosis are sparse and conflicting. From 1990-3, 235 of our 240 patients (114 males, 121 females, median age 16.2 years, ranged 0.1-44.0 years) had IGF-I measured once by radioimmunoassay. IGF-I was significantly reduced compared with a healthy Scandinavian control population: mean (-2 SD to +2 SD) IGF-I SD score was -0.97 (-3.7 to 1.7) in males and -0.67 (-3.2 to 1.9) in females. Height SD score was -0.95 (-3.3 to 1.4) in males and -0.81 (-3.2 to 1.6) in females. In patients who were still in the growth period a significant correlation of IGF-I SD score to height SD score (r = 0.28, p < 0.001) was found. The low IGF-I concentrations may reflect the catabolic state of many patients with cystic fibrosis and play a part in their abnormal growth pattern.     

Probiotic effects on faecal inflammatory markers and on faecal IgA in food allergic atopic eczema/dermatitis syndrome infants

Probiotic bacteria are proposed to alleviate intestinal inflammation in infants with atopic eczema/dermatitis syndrome (AEDS) and food allergy. In such infants we investigated effects of probiotic bacteria on faecal IgA, and on the intestinal inflammation markers tumour necrosis factor-alpha (TNF-alpha), alpha1-antitrypsin (AT), and eosinophil cationic protein (ECP). A total of 230 infants with AEDS and suspected cow's milk allergy (CMA) received in a randomized double-blinded manner, concomitant with elimination diet, Lactobacillus GG (LGG), a mixture of four probiotic strains (MIX), or placebo for 4 wk. Four weeks after treatment, CMA was diagnosed with a double-blind placebo-controlled milk challenge. Faecal samples of 102 infants, randomly chosen for analysis, were collected before treatment, after 4-wk treatment, and on the first day of milk challenge. After treatment, IgA levels tended to be higher in probiotic groups than in the placebo group (LGG vs. placebo, p=0.064; MIX vs. placebo, p=0.064), and AT decreased in the LGG group, but not in other treatment groups. After challenge in IgE-associated CMA infants, faecal IgA was higher for LGG than for placebo (p=0.014), and TNF-alpha was lower for LGG than for placebo, but non-significantly (p=0.111). In conclusion, 4-wk treatment with LGG may alleviate intestinal inflammation in infants with AEDS and CMA.     

A similar high level of immunoglobulin A and immunoglobulin G class milk antibodies and increment of local lymphoid tissue on the duodenal mucosa in subjects with cow's milk allergy and recurrent abdominal pains

In previous studies, we have reported endoscopic and histological alterations locally on the gastrointestinal (GI) tract associated with a gastrointestinal type of cow's milk allergy. In this study, we sought to further characterize endoscopic, and immunological findings in these children. We also hypothesized that the same type of immune responses might also be found in children with unexplained and recurrent abdominal pains. We did a gastroduodenoscopy for persistent GI symptoms, examined the mucosal histology of the small intestine and measured the antibodies to whole cow's milk and its fractions with an enzyme‐linked immunosorbent assay (ELISA) in a consecutive series of 22 subjects with untreated and 14 with treated cow's milk allergy (CMA) and 44 with recurrent abdominal pains (RAP). The immunological findings of the study subjects were compared with 54 controls. Lymphonodular hyperplasia (LNH) of the duodenum was the main endoscopic finding in 11 subjects (50%) with untreated and 5 (36%) with treated CMA. It was also found in 6 of 44 subjects with RAP. Compared with the controls, the patients with CMA showed significantly higher levels of IgA class antibodies to whole milk (p = 0.003) and βLG (p < 0.0001). Of the IgG class antibodies to βLG (p = 0.032), BSA (p < 0.0001) and αCAS (p < 0.0001) were significantly higher. The patients with LNH of the duodenal bulb as the main endoscopic finding showed significantly higher values of IgG class antibodies to βLG (p = 0.01) and αCAS (p = 0.005). Interestingly, the patients examined for RAP showed a similar increment in the pattern of whole milk and specific milk protein antibodies as the CMA children. In conclusion this study showed that gastrointestinal CMA beyond infancy is significantly associated with high levels of IgG and IgA class antibodies to milk and its fractions. As high levels of these antibodies and LNH of the duodenal bulb were also found in subjects with RAP, the study further suggests that gastrointestinal CMA might be one major reason for RAP.     

Physiological anticoagulants and activated protein C resistance in childhood stroke

Immunological and functional protein S, protein C and antithrombin III levels and anticoagulant responses to activated protein C were measured in 24 patients with stroke in childhood. No hereditary deficiencies were found. The protein S levels in healthy controls of younger age did not differ from the adult levels. For optimal screening of protein S deficiency, measurements using functional as well as immunological assays are recommended. Appropriate criteria for the diagnosis of the deficiencies must be carefully applied if unnecessary anxiety and inappropriate treatment of children are to be avoided.     

Evaluation of attempted prevention of unexpected infant death in very high-risk infants by planned health care

Three hundred and ninety-six babies born in Sheffield between 1982 and 1990 identified as being at "very high risk" of unexpected infant death by means of a scoring system, received an intensive programme of health care including a case discussion between a paediatrician, the GP and the health visitor held in the family doctor's surgery, weekly visits from the health visitor and informal hospital admission. Significantly fewer sudden unexpected infant deaths occurred in this group than were expected by logistic regression anlysis or occurred in the best available control group with comparable scores ( p = 0.024). Problems in evaluation include identification of an adequate control population, ethical difficulties in introducing a controlled study when the programme is already perceived as effective, and the calculation of "expected death rates". The results of this study indicate that very energetic programmes of intervention may prevent some deaths in vulnerable infants.     

IgA deficiency in children: A clinical study with special reference to intestinal findings

Clinical, immunological, and intestinal studies on 26 children with IgA deficiency in the age range 2 to 16 years are reported. 9 of these children were suffering from autoimmune disease, namely thyroiditis (5), thyrotoxicosis (1), rheumatoid arthritis (2), and probable Sjögren''s syndrome (1). The last-mentioned patient had defective cellular immunity. Altogether 11 patients were subject to recurrent respiratory tract infections. The symptomatology of the remaining patients was variable. In a boy with growth retardation, a chromosome anomaly was found, and endocrinological studies indicated total absence of growth hormone.In 21 patients IgA was undetectable, while 5 had trace amounts of IgA in their sera. IgG was raised in 11 patients, and one patient had low serum IgG. IgM levels were mostly normal. Precipitating antibodies to cow''s milk proteins were present in all but one serum.Small intestinal biopsy was performed on all patients. In 3 cases total villous atrophy was detected and these probably had coeliac disease, though malabsorption symptoms were not always evident. Disaccharidase assay of biopsy specimens revealed 2 cases of isolated lactase deficiency among 8 tested.Results show that the increased incidence of autoimmune disease reported in IgA deficiency in adults also holds true in children; i.e. that there is a raised incidence of coeliac disease with or without symptoms in IgA deficiency.     

Fibromatosis of bone in children

Radiographs, computed tomograms, and radionuclide bone scans were obtained preoperatively in three children with fibromatosis involving the bones and soft tissues of the extremities. Two of the children had identical scar-like bone lesions of the proximal tibia, which, to the authors' knowledge, have not been reported before in this disease. The lesions recurred in two children.