An increased level of antibodies to beta-lactoglobulin is a risk determinant for early-onset type 1 (insulin-dependent) diabetes mellitus independent of islet cell antibodies and early introduction of cow's milk.
Using a case-control design we have studied whether antibodies to cow's milk proteins are risk determinants for childhood-onset Type 1 (insulin-dependent) diabetes mellitus independent of early exposure to cow's milk formula and islet cell antibodies. Sera from 116 recent-onset diabetic children and 112 age- and sex-matched control children were analysed for cow's milk protein IgA, IgG and IgM antibodies, beta-lactoglobulin IgA and IgM antibodies and islet cell antibodies. The titres were compared to questionnaire data on duration of breast-feeding and introduction of formula feeding. Most antibody levels tended to be increased among diabetic compared to control children. This was statistically significant for cow's milk protein IgA antibodies (p less than 0.001) and beta-lactoglobulin IgA antibodies (p less than 0.01) as well as for islet cell antibody-positivity which was found among 92% of the diabetic and 3% of control children. The differences in cow's milk protein antibodies as well as beta-lactoglobulin antibodies were more pronounced among children with an early onset of Type 1 diabetes. Breast-feeding duration was significantly inversely related to the log of beta-lactoglobulin IgG (r = -0.16, p = 0.04) and the log of cow's milk protein IgA antibodies (r = -0.17, p less than 0.001). A positive correlation was found between formula feeding and the logarithm of beta-lactoglobulin IgG antibodies (r = 0.22, p = 0.01) and the log of cow's milk protein IgA antibodies (r = 0.16, p = 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)
We have measured antibodies to gliadin (AGA), bovine beta-lactoglobulin, and chicken egg ovalbumin with a four-layer solid phase radioimmunoassay (RIA) in 62 children and adolescents with coeliac disease and in 36 healthy controls. The geometric mean titre of IgG AGA in patients at initial diagnosis was more than 100-fold that of controls (p less than 0.0001). Even patients on gluten-free diet had significantly higher IgG AGA titres than the controls (p = 0.0001), the difference being more than 5-fold. All the 42 patients with active disease (30 at initial diagnosis and 12 after gluten challenge) had their IgG AGA titre above 1,000, as compared with 2 (5.7%) of the 35 controls (p less than 0.0001). Both IgG and IgA AGA were quite sensitive and specific in identifying children with coeliac disease; the sensitivities for IgG and IgA AGA were 100% and 95.2%, the specificities 94.3% and 97.2%, respectively. We conclude that determination of IgG and IgA AGA with RIA is suitable for monitoring dietary compliance in children with coeliac disease, and the method is sensitive and specific for screening for coeliac disease in children.
Congenital lactase deficiency (CLD) is an autosomal recessive, gastrointestinal disorder characterized by watery diarrhea starting during the first 1-10 d of life, in infants fed lactose-containing milks. Since 1966, 42 patients have been diagnosed in Finland. CLD is the most severe form of lactase deficiency, with an almost total lack of lactase-phlorizin hydrolase (LPH) activity on jejunal biopsy. In adult-type hypolactasia, the most common genetic enzyme deficiency in humans, this enzyme activity is reduced to 5%-10%. Although the activity of intestinal LPH has been found to be greatly reduced in both forms, the molecular pathogenesis of lactase deficiencies is unknown. On the basis of the initial candidate-gene approach, we assigned the CLD locus to an 8-cM interval on chromosome 2q21 in 19 Finnish families. At the closest marker locus, a specific allele 2 was present in 92% of disease alleles. On the basis of a genealogical study, the CLD mutation was found to be enriched in sparsely populated eastern and northern Finland, because of a founder effect. The results of both the genealogical study and the haplotype analysis indicate that one major mutation in a novel gene causes CLD in the Finnish population. Consequently, the critical region could be restricted further, to an approximately 350-kb interval, by ancient-haplotype and linkage-disequilibrium analyses. Surprisingly, the LPH gene was shown to lie outside the critical CLD region, excluding it as a causative gene for CLD. The LPH locus was found to reside >2 Mb from the critical CLD region.
The clinical course of alpha-chain disease in a Finnish boy is described. The disease presented with growth retardation and gastrointestinal symptoms at age 10 yr. Tests performed between the ages of 15 and 21 yr showed varying intestinal involvement including the large bowel, ileum, and distal jejunum. Alpha-chain disease protein was present in serum in fluctuating concentrations for at least 5 yr; it was produced by plasmacytoid cells found in the affected parts of the large bowel mucosa. The patient was treated with sulfasalazine and melphalan, but it is not clear that the clinical remission and the subsequent disappearance of the alpha-chain disease protein should be ascribed to this treatment. Concomitant with the normalization of the condition, a selective immunoglobulin A deficiency became apparent. The possibility is raised that an immunoglobulin A deficiency could have been the original defect in the patient, predisposing to intestinal infections; topical overstimulation of a defective immunoglobulin A system due to impaired mucosal defense might thus have explained the emergence of alpha-chain disease cells in the gut.
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.
Children with high body mass index (BMI) at preschool age are at risk of developing obesity. Early identification of factors that increase the risk of excessive weight gain could help direct preventive actions. The intestinal microbiota and antibiotic use have been identified as potential modulators of early metabolic programming and weight development. To test if the early microbiota composition is associated with later BMI, and if antibiotic use modifies this association, we analysed the faecal microbiota composition at 3?months and the BMI at 5-6?years in two cohorts of healthy children born vaginally at term in the Netherlands (N?=?87) and Finland (N?=?75). We obtained lifetime antibiotic use records and measured weight and height of all children.
The relative abundance of streptococci was positively and the relative abundance of bifidobacteria negatively associated with the BMI outcome. The association was especially strong among children with a history of antibiotic use. Bacteroides relative abundance was associated with BMI only in the children with minimal lifetime antibiotic exposure.
The intestinal microbiota of infants are predictive of later BMI and may serve as an early indicator of obesity risk. Bifidobacteria and streptococci, which are indicators of microbiota maturation in infants, are likely candidates for metabolic programming of infants, and their influence on BMI appears to depend on later antibiotic use.
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To study the humoral immune response to bovine serum albumin (BSA) and ovalbumin (OA) in children with newly diagnosed insulin-dependent diabetes mellitus (IDDM).
We examined serum samples from 505 children 0.8-14.9 years of age with newly diagnosed IDDM for antibodies to BSA and OA by enzyme-linked immunosorbent assay (ELISA). We also had two control groups: 85 unrelated control children (0.8-7.1 years of age) and 395 nondiabetic siblings (3.0-14.9 years of age). The specificity of antibodies detected in ELISA was confirmed by immunoblotting in a subset of sera with varying levels of antibodies.