High levels of omega-3 fatty acids in milk from omega-3 fatty acid-supplemented mothers are related to less immunoglobulin E-associated disease in infancy.

AIM: We previously reported a protective effect of maternal omega-3 fatty acid supplements on the development of immunoglobulin E (IgE)-associated disease in infancy. This study assessed omega-3 long-chain polyunsaturated fatty acids (LCPUFA) in maternal milk in relation to omega-3 LCPUFA supplementation and the development of allergic disease in their infants. METHODS: This study randomised 95 pregnant women at risk of having an allergic infant, to daily supplements of 2.6 g omega-3 LCPUFA or a placebo of 2.7 g soya bean oil from gestational week 25 until 3 months of lactation. Breast milk samples were collected as colostrum, at one and 3 months. Milk fatty acids were related to allergic outcome in the infants at 24 months. RESULTS: Omega-3 milk fatty acids were higher in women who received omega-3 supplements than the placebo group (p < 0.01). Higher proportions of milk eicosapentaenoic acid and docosahexaenoic acid and a lower arachidonic/eicosapentaenoic acid ratio were associated with an absence of IgE-associated disease in the infants. None of the children developed IgE-associated atopic eczema above a level of 0.83 mol% eicosapentaenoic acid in colostrum. [Correction added on 7 July 2016, after online publication: In the preceding sentence, the correct word should be "above" instead of "below" and this has been amended in this current version.] CONCLUSION: High omega-3 LCPUFA milk levels in mothers who received omega-3 LCPUFA supplements were related to fewer allergies in their children.

Expression pattern of T-helper 17 cell signaling pathway and mucosal inflammation in celiac disease.

OBJECTIVE: The aim was to investigate the mucosal activation of a broad range of genes associated with the T-helper 17 cell (Th17) signaling pathway in children at different stages of celiac disease (CD), including children with increased risk for CD and children with untreated and gluten-free diet (GFD)-treated CD. MATERIAL AND METHODS: Small intestinal biopsies were taken from children with untreated and GFD-treated CD, transglutaminase antibody (TGA)-positive children with potential CD, and reference children. Real-time polymerase chain reaction (PCR) arrays were used to study the gene expression pattern of Th17-related genes, and quantitative PCR was used to study the interleukin (IL)-17A expression. RESULTS: The mucosal expression of CD8A was elevated at all stages of CD. Children with untreated CD had diminished levels of IL-17RE, IL-23R, RORc, STAT6, CCL22, NFATC2, IL-18, CD4, CD247, and matrix metalloproteinase (MMP)9 but had elevated levels of MMP3, IL-17, interferon-γ (IFN-γ) and CD8A, compared to references. The majority of the aforementioned genes, being differentially expressed in untreated CD, displayed similar expression in GFD-treated children and references. Children with untreated and GFD-treated CD had elevated expression of IFN-γ but had reduced expression of CD247. Interestingly, children with potential CD displayed reduced FOXP3, IL-21, and IL-17A levels. CONCLUSION: Mucosal upregulation of Th17 immunity occurs at the late stage of disease and is downregulated with dietary treatment, thus indicating that IL-17 immunity is not a fundamental feature of CD as Th1 immunity, which is not fully downregulated by GFD.

Urinary nitric oxide metabolites in children with celiac disease after long-term consumption of oats-containing gluten-free diet.

OBJECTIVE: Oats are accepted in the gluten-free diet (GFD) for children with celiac disease (CD). Some reports have indicated, however, that not all celiac patients tolerate oats. We have previously shown that some children still have high levels of urinary nitric oxide (NO) metabolites as markers of intestinal inflammation after 1 year on GFD with oats. In this study, we measured urinary NO metabolites in CD children who had been consuming oats-containing GFD for an extended, 2-6-year period, also taking into consideration ordinary consumption of nitrite/nitrate-rich foods close to the urine sampling. MATERIALS AND METHODS: Morning urinary nitrite/nitrate concentrations were measured in 188 pediatric CD patients. A questionnaire was used to elucidate factors possibly affecting the urinary levels, for example, dietary factors, asthma, or urinary tract infection. RESULTS: Oats were consumed by 89.4% of the patients for a median time of 3 years. The median nitrite/nitrate level was 980 µM. The majority (70.2%) who consumed oats had low levels of urinary nitrite/nitrate, that is, <1400 µM, while 29.8% demonstrated high levels, that is, >1400 µM. Nitrite/nitrate-rich foods did not significantly influence the urinary concentrations. CONCLUSION: The urinary levels of NO metabolites revealed two subpopulations, one with high and one with low levels. The high levels could be possibly due to poor adherence to the GFD, sensitivity to oats, or some unknown factor(s). Nitrate-rich foods, asthma, or urinary tract infection did not affect the result. The elevated levels of NO metabolites could indicate mucosal inflammation and pinpoint the need of careful follow-up of children on oats-containing GFD.

Faecal short-chain fatty acid pattern in childhood coeliac disease is normalised after more than one year's gluten-free diet.

OBJECTIVE: Recent work indicates that the gut microflora is altered in patients with coeliac disease (CD). Faecal short-chain fatty acids (SCFAs) are produced by the gut microflora. We have previously reported a high SCFA output in children with symptomatic and asymptomatic CD at presentation, as well as in CD children on a gluten-free diet (GFD) for less than 1 year, indicating deviant gut microfloral function. In this report, we focus on faecal SCFA production in coeliacs on GFD for more than 1 year. MATERIALS AND METHODS: Faecal samples were collected from 53 children with CD at presentation, 74 coeliac children on GFD for less than 1 year, and 25 individuals diagnosed with CD in childhood and on GFD for more than 1 year. The control group comprised 54 healthy children (HC). The faecal samples were analysed to show the SCFA pattern taken as a marker of gut microflora function. We applied a new fermentation index, reflecting the inflammatory activity of the SCFAs (amount of acetic acid minus propionic acid and n-butyric acid, together divided by the total amount of SCFAs). RESULTS: In coeliacs on GFD for more than 1 year, the individual SCFAs, total SCFA, and fermentation index did not differ significantly from the findings in controls. In contrast, the faecal SCFA level was clearly higher in coeliacs treated with GFD for less than 1 year compared to those more than 1 year. CONCLUSIONS: This is the first study on SCFA patterns in faecal samples from individuals with CD on GFD for more than 1 year. Our study indicates that the disturbed gut microflora function in children with CD at presentation and after less than 1 year of GFD, previously demonstrated by us, is normalised on GFD for more than 1 year.

Th1 and Th2 chemokines, vaccine-induced immunity, and allergic disease in infants after maternal ω-3 fatty acid supplementation during pregnancy and lactation.

We investigated whether the previously reported preventive effect of maternal ω-3 fatty acid supplementation on IgE-associated allergic disease in infancy may be mediated by facilitating a balanced circulating Th2/Th1 chemokine profile in the infant. Vaccine-induced immune responses at 2 y of age were also evaluated. Pregnant women, at risk of having an allergic infant, were randomized to daily supplementation with 1.6 g eicosapentaenoic acid and 1.1 g docosahexaenoic acid or placebo from the 25th gestational week through 3.5 mo of breastfeeding. Infant plasma was analyzed for chemokines (cord blood, 3, 12, 24 mo) and anti-tetanus and anti-diphtheria IgG (24 mo). High Th2-associated CC-chemokine ligand 17 (CCL17) levels were associated with infant allergic disease (p < 0.05). In infants without, but not with, maternal history of allergy, the ω-3 supplementation was related to lower CCL17/CXC-chemokine ligand 11 (CXCL11) (Th2/Th1) ratios (p < 0.05). Furthermore, in nonallergic, but not in allergic infants, ω-3 supplementation was linked with higher Th1-associated CXCL11 levels (p < 0.05), as well as increased IgG titers to diphtheria (p = 0.01) and tetanus (p = 0.05) toxins. Thus, the prospect of balancing the infant immune system toward a less Th2-dominated response, by maternal ω-3 fatty acid supplementation, seems to be influenced by allergic status.

Allergic disease in infants up to 2 years of age in relation to plasma omega-3 fatty acids and maternal fish oil supplementation in pregnancy and lactation.

We have previously reported a protective effect of maternal omega-3 long-chain polyunsaturated fatty acids (ω-3 LCPUFA) supplementation in pregnancy and lactation on IgE-associated eczema and food allergy in the infant during the first year of life. Here we investigate whether the effects of the LCPUFA supplementation on IgE-associated diseases last up to 2 yr of age and assess the relationship between plasma proportions of ω-3 PUFAs and the frequency and severity of infant allergic disease. 145 pregnant women, at risk of having an allergic infant, were randomized to daily supplementation with 1.6 g eicosapentaenoic acid (EPA) and 1.1 g docosahexaenoic acid (DHA) or placebo starting in the 25th gestational week and continuing through 3.5 months of breastfeeding. Clinical examinations, skin prick tests and analysis of maternal and infant plasma phospholipid fatty acids and infant specific IgE were performed. No difference in the prevalence of allergic symptoms was found between the intervention groups. The cumulative incidence of IgE-associated disease was lower in the ω-3-supplemented group (6/54, 13%) compared with the placebo group (19/62, 30%, p=0.01). Higher maternal and infant proportions of DHA and EPA were associated with lower prevalence of IgE associated disease (p=0.01-0.05) in a dose-dependent manner. Higher maternal and infant proportions of DHA and EPA were found if the infants presented none, when compared with multiple allergic symptoms, (p<0.05) regardless of sensitization. In summary, the ω-3 supplementation offered no obvious preventive effect on the prevalence of clinical symptoms of allergic disease, but the decrease in cumulative incidence of IgE-associated disease seen during the first year still remained until 2 yr of age. Furthermore, high proportions of DHA and EPA in maternal and infant plasma phospholipids were associated with less IgE-associated disease and a reduced severity of the allergic phenotype.

The effect of gluten-free diet on Th1-Th2-Th3-associated intestinal immune responses in celiac disease.

OBJECTIVE: To study T-helper (Th)1-Th2-Th3 gene activation profile in the small intestine and peripheral blood of children with celiac disease (CD) with special interest in the response to the gluten-free diet (GFD) treatment in order to elucidate an immune dysregulation not triggered by gluten. MATERIAL AND METHODS: Small intestinal biopsies and venous blood were taken from seven children with CD (mean age: 8 years, four girls) at presentation and after 1 year of strict GFD. The Th1-Th2-Th3 gene expression profile was examined by real-time PCR arrays. The findings were compared with the corresponding expressions in peripheral blood and small intestinal biopsies from six reference children without CD (mean age: 6 years, four girls). RESULTS: The Th1 gene expression profile including interferon (IFN)-γ, signal transducer and activator of transcription (STAT) 1 and interferon regulatory factor (IRF) 1 together with reduced interleukin (IL)-2 expression was pronounced in small intestinal biopsies from children with untreated CD. A downregulation of IFN-γ transcripts was seen after 1 year of GFD, but there was still increased expression of STAT1 and IRF1 in association with low IL-2 expression in spite of eliminated exposure to wheat gluten. By contrast, the decreased intestinal expression of Th2 gene markers observed at presentation was normalized with GFD. The alterations in the mucosal gene expression profile were not reflected in peripheral blood. CONCLUSION: The GFD did not correct the increased activation of the IFN-γ signaling pathway related markers and reduced IL-2 expression, suggesting that they represent an immune dysregulation not dependent on gluten exposure.

Dysregulated Th1 and Th2 responses in food-allergic children--does elimination diet contribute to the dysregulation?

Infants with eczema and sensitization to foods are recommended skin care and, if food allergy is proven, an elimination diet. Although most of these children tolerate foods before 3 yr of age, some children experience prolonged food allergy. To our knowledge, no prospective study has investigated the cytokine profile in food-sensitized eczematous children with prolonged food intolerance. The aim of the study was to prospectively investigate the development of cytokine production induced by food allergen in food-sensitized eczematous children who, at 4(1/2) yr of age, were allergic or tolerant to egg or milk. Twenty-one eczematous infants, [age 5 (3-10) months; median and range], sensitized to egg and/or milk were included, put on elimination diet and followed prospectively. At 4(1/2) yr of age, the children were defined as tolerant or allergic to egg and/or milk based on open or double-blind placebo-controlled food challenges. Peripheral blood mononuclear cells (PBMC) were isolated from the children on inclusion, after 6 wk of elimination diet, and at 3 and 4(1/2) yr of age. Ovalbumin, beta-lactoglobulin and tetanus toxoid-induced IL-4, -5, -10, -13 and IFN-gamma production from PBMC were analyzed with enzyme-linked immunosorbent assay. The IFN-gamma and IL-5 secretion induced by food allergen at 4(1/2) yr was higher in cell cultures from children who were allergic to egg or milk than in tolerant children. In food-allergic children, the levels of IFN-gamma and IL-5 were higher at 4(1/2) yr compared with inclusion levels, but this increase was generally not observed in the tolerant children who consumed milk and egg. In conclusion, immune cells from food-allergic children on an elimination diet respond with up-regulated T helper 1 and T helper 2 cytokine secretion induced by food allergen. We hypothesize that allergen elimination may influence the regulatory mechanisms maintaining balanced immune responses to innocuous food antigens.

Urinary nitric oxide excretion in infants with eczema.

Eczema is characterized by inflammation of the skin and is commonly associated with food allergy. It has been suggested that nitric oxide (NO) is an important player in eczema, food allergy and intestinal inflammation. The aim of this study was to assess the levels of urinary NO breakdown products in infants with eczema and the effect of eczema treatment on NO levels. Ninety-four infants with eczema, 58 boys and 36 girls, with a mean age of 7.5 ± 5.2 months (mean ± s.d.) at inclusion were examined twice with an interval of 6 wk. The sum of nitrite and nitrate was measured colorimetrically in urinary samples from both visits and compared with clinical data concerning eczema severity, nutrition, gastrointestinal symptoms, asthma and skin prick positivity. The levels of NO products increased significantly from the first to the second visit: 289; 374 µm (median; IQR) vs. 457; 678 µm (median; IQR) (p < 0.001) in parallel with a significant improvement of the eczema. After eczema treatment consisting of skin care and elimination diet during the 6-wk interval between evaluations, the NO levels approached the values previously found in healthy children. The results support previous studies indicating that the homeostasis of nitrogen radicals is disturbed in childhood eczema.

Screening-detected and symptomatic untreated celiac children show similar gut microflora-associated characteristics.

OBJECTIVE: The aim of this study was to investigate the metabolic function of intestinal microflora in children with screening-detected celiac disease (CD) to see if there is an aberrant gut flora in screening-detected CD similar to symptomatic CD and contrary to healthy controls. MATERIALS AND METHODS: As part of a Swedish multicenter screening for CD, 912 12-year-old children were screened with serum anti-human tissue transglutaminase-IgA. Small bowel biopsy specimens from children with positive serology revealed 17 individuals with CD. The functional status of the intestinal microflora was evaluated by gas-liquid chromatography of short chain fatty acids (SCFAs) in fecal samples. Our previously published findings in children with symptomatic CD and healthy controls were used as comparison. RESULTS: The children with screening-detected CD had a similar fecal SCFA profile to children with symptomatic CD, but differed significantly from that in healthy children. CONCLUSIONS: This is the first study on SCFA patterns in fecal samples from children with screening-detected CD. The similarity of the fecal SCFA profile in screening-detected and symptomatic CD indicates common pathogenic mechanisms. This could open the way for new therapeutic or prophylactic measures based on novel biological principles.

The effects of omega-3 fatty acid supplementation in pregnancy on maternal eicosanoid, cytokine, and chemokine secretion.

The incidence of allergic diseases has increased, and a relation between allergy and dietary fatty acids has been proposed. Modulation of the maternal immune function during pregnancy may have an impact on future clinical outcomes in the child. The aim of this study was to determine the effects of omega (omega)-3 long-chain polyunsaturated fatty acids (LCPUFA) supplementation during pregnancy on the plasma fatty acid composition in relation to the maternal immune function. Pregnant women with allergic disease in their immediate family were supplemented daily with 2.7 g omega-3 LCPUFA (n = 70) or 2.8 g soybean oil as placebo (n = 75) from the 25th gestational week. The proportions of eicosapentaenoic acid and docosahexaenoic acid in plasma/serum phospholipids increased in the omega-3-supplemented group, whereas arachidonic acid decreased during intervention. Lipopolysaccharide-induced prostaglandin E2 secretion from whole blood culture supernatants (n = 59) decreased in a majority of the omega-3-supplemented mothers (18 of 28, p = 0.002). The decreased prostaglandin E2 production was more pronounced among nonatopic than atopic mothers. The lipopolysaccharide-induced cytokine and chemokine secretion was not affected. Our results indicate that omega-3 LCPUFA supplementation during the last trimester may dampen certain immune responses involved in allergic inflammation.

Adverse reactions to skin prick testing in children - prevalence and possible risk factors.

Skin prick test (SPT) is usually considered to be a safe procedure, but recently there have been occasional case reports of generalized allergic reactions. This study was performed to delineate the prevalence of, and evaluate possible risk factors for, adverse reactions to SPT in a prospective study. Altogether 5,908 patients aged < or =18 yr from 11 different pediatric settings were included. The adverse reactions were classified into two groups: (1) Generalized allergic reactions (GAR), (2) Vasovagal reactions (VVR). Adverse reactions were observed in 14 out of 5,908 children examined with SPT. Seven of the adverse reactions were GARs and required medication, yielding a 0.12% risk for GAR. Seven of 14 were VVRs, giving the same risk, 0.12%. Identified risk factors for GAR were low age (<1 yr) (RR 6.28) and active eczema (RR 16.98). For VVR, the risk factors were female sex (RR 7.32) and multiple skin pricks performed on a single patient (p < 0.05). We conclude that GARs do occur, albeit rarely, so the need for proper emergency handling should always be acknowledged. The risk factors suggested may help to identify patients who need extra attention.

High levels of IgG4 antibodies to foods during infancy are associated with tolerance to corresponding foods later in life.

Children with eczema and sensitization to foods are recommended skin care and, if food allergy is proven by challenge, an elimination diet. For most children the diet period is transient, but the process behind tolerance development and the influence of decreased allergen exposure is not fully known. The aim of the study was to investigate the effect of elimination diet on serum and salivary antibodies and to identify immunological parameters related to the ability to tolerate foods. Eighty-nine children, below 2 yr of age, with eczema and suspected food allergy were included. Recommended treatment was skin care to all children, and 60 children had a period of elimination diet. At 4(1/2) yr of age, the children were divided into two groups, based on if they had been able to introduce the eliminated foods, or not. Serum and salivary antibodies were analyzed with enzyme-linked immunosorbent assay and UniCAP before and after a 6-wk treatment period and at 4(1/2) yr of age. Children sensitized to egg and/or milk that could eat and drink the offending foods at 4(1/2) yr of age, had higher levels of Immunoglobulin G(4) antibodies to ovalbumin and beta-lactoglobulin and also higher IgG(4)/Immunoglobulin E ratios on inclusion in the study, than those who had to eliminate egg and/or milk from their diet, beyond 4(1/2) yr of age. The highest IgG(4)/IgE ratios were found in children with circulating IgE antibodies to egg and/or milk but negative skin prick test on inclusion. The 6-wk treatment period did not significantly affect the levels of serum and salivary antibodies. In conclusion, eczematous, food sensitized infants with high levels of IgG(4) and high ratios of IgG(4)/IgE antibodies to food allergens are more likely to consume these foods at 4(1/2) yr than infants with low levels and ratios.

Fish oil supplementation in pregnancy and lactation may decrease the risk of infant allergy.

UNLABELLED: Maternal intake of omega-3 (omega-3) polyunsaturated fatty acids (PUFAs) during pregnancy has decreased, possibly contributing to a current increased risk of childhood allergy. AIM: To describe the effects of maternal omega-3 long-chain PUFA supplementation during pregnancy and lactation on the incidence of allergic disease in infancy. METHODS: One hundred and forty-five pregnant women, affected by allergy themselves or having a husband or previous child with allergies, were included in a randomized placebo-controlled trial. Daily maternal supplementation with either 1.6 g eicosapentaenoic acid and 1.1 g docosahexaenoic acid or placebo was given from the 25(th) gestational week to average 3-4 months of breastfeeding. Skin prick tests, detection of circulating specific immunoglobulin E (IgE) antibodies and clinical examinations of the infants were performed. RESULTS: The period prevalence of food allergy was lower in the omega-3 group (1/52, 2%) compared to the placebo group (10/65, 15%, p < 0.05) as well as the incidence of IgE-associated eczema (omega-3 group: 4/52, 8%; placebo group: 15/63, 24%, p < 0.05). CONCLUSION: Maternal omega-3 fatty acid supplementation may decrease the risk of food allergy and IgE-associated eczema during the first year of life in infants with a family history of allergic disease.

The clinical presentation of coeliac disease in 1030 Swedish children: Changing features over the past four decades.

BACKGROUND: The features of paediatric coeliac disease have changed in recent decades. We hypothesised that the age at diagnosis might continue to increase, whereas the severity of symptoms should decrease. METHODS: In the present study, filed data on 1030 paediatric patients diagnosed with coeliac disease between 1973 and 2013 were analysed. The information available covered 99.8% of small bowel biopsies and included information on sex, age and clinical symptoms. RESULTS: The age at diagnosis increased significantly, from a mean of 2.2 years during the first 10 years to 8.2 years in recent years. The proportion of children with severe symptoms declined from 92.8% to 78%, as did the proportion of biopsies characterised by severe pathology. In recent years, the monosymptomatic form of coeliac disease has been more common, and the number of patients detected at screening has increased. The frequency of patients with gastrointestinal symptoms, extra-intestinal symptoms, and failure to thrive and/or short stature at presentation decreased. CONCLUSIONS: The mean age of newly diagnosed patients has increased over the last 15 years. Currently, coeliac disease shows a less severe picture in terms of symptoms and intestinal pathology. Younger children suffer primarily from gastrointestinal symptoms and growth failure, and adolescents from extra-intestinal manifestations.

Evaluation of Multiple Diagnostic Indicators in Comparison to the Intestinal Biopsy as the Golden Standard in Diagnosing Celiac Disease in Children.

Celiac disease (CD) is a chronic small intestinal enteropathy triggered by gluten in genetically predisposed individuals. The susceptibility is strongly associated with certain human leukocyte antigen (HLA)-genes, but efforts are being made in trying to find non-HLA genes that are predictive for the disease. The criteria for diagnosing CD were previously based primarily on histologic evaluation of small intestinal biopsies, but nowadays are often based only on blood tests and symptoms. In this context, we elucidated the accuracy of three diagnostic indicators for CD, alone or in combination. Genetic analyses of HLA-type and nine single nucleotide polymorphisms (SNPs) known to be associated with CD were performed in 177 children previously investigated for the suspicion of CD. CD was confirmed in 109 children, while 68 were considered non-celiacs. The antibodies and urinary nitrite/nitrate concentrations of all of them were measured. The combinations of all the variables used in the study would classify 93% of the study population in the correct diagnostic group. The single best predictors were antibodies (i.e., anti-endomysium immunoglobulin A (IgA) (EMA) and transglutaminase IgA (TGA)), followed by HLA-type and nitric oxide (NO)-metabolites. The nine SNPs used did not contribute to the right diagnoses. Although our control group consisted of children with mostly gastrointestinal symptoms, the presented methodology predicted a correct classification in more than 90% of the cases.

Unusually High Incidence of Paediatric Coeliac Disease in Sweden during the Period 1973 - 2013.

OBJECTIVE: The prevalence of coeliac disease in Sweden during the "epidemic period" (1984-1996) was one of the highest in the world. The aim of this study was to assess the coeliac disease incidence in our region over the 41-year period, and how diagnostic activity and diagnostic accuracy were affected by the introduction of antibody testing. We also looked into how patients with mild enteropathy were evaluated. METHODS: In the county of Östergötland in Sweden, 2790 paediatric patients were investigated for suspected coeliac disease between 1973 and 2013. Notes were scrutinised for data on sex, age, histopathological reports and final diagnosis. For comparative purposes this period was divided into three sub-periods (1973-1983, 1984-1996 and 1997-2013) named pre-epidemic, epidemic and post-epidemic. RESULTS: Coeliac disease diagnosis was received by 1,030 patients. The peak incidence rate, 301 cases/100,000 in 1994 for the age group 0-1.9 years is the highest figure ever reported. The other age groups, 2-4.9, 5-14.9, and 15-17.9 years, also had high incidence rates. After the 1984-1996 "epidemic period" the incidence decreased for the youngest group but continued to increase for the other groups. The cumulative incidence at 18 years-of-age for children born during the epidemic reached 14 cases/1000 births, the highest figure hitherto reported. Diagnostic activity differed significantly between the three sub-periods (p<0.001) increasing gradually from 1984 and reaching a peak value of 0.87 in 2012. Cases of mild enteropathy were more frequently regarded as non-coeliac disease cases, decreasing significantly in the "post-epidemic" period (p<0.001). CONCLUSIONS: The incidence rate and cumulative incidence of coeliac disease were possibly the highest ever reported. Changes in diagnostic activity and accuracy could not be attributed to the introduction of new antibody tests, possibly because of other changes e.g. variations in the symptoms at presentation and improved knowledge of the disease among parents and health professionals.

Induction of diabetes-related autoantibodies below cutoff for "positivity" in young nondiabetic children.

The aim was to study the natural course of diabetes-related autoantibodies at low concentrations, below "positivity", in a nondiabetic population followed up from infancy. Blood samples were taken from 205 children at 6 weeks, 6 months, 18 months, and 5 years of age. Autoantibodies against GAD(65) (GADA), tyrosine phosphatase (IA-2A), and insulin (IAA) were determined by radioligand-binding assays. All children had detectable levels of GADA and approximately half had IA-2A, but only approximately 10% had detectable levels of IAA during the follow-up period. Many children developed IA-2A already at 6 months of age, similar concentrations were seen at 18 months, and then the levels of IA-2A decreased until 5 years of age. GADA were induced less often at 6 months of age, increased up to 18 months, and fluctuated at similar levels up to 5 years of age. IAA were detectable in so few children and at low levels, so no trend in natural course could be revealed. We conclude that there is a natural induction of humoral immune response to beta cell autoantigens early in life. Our results suggest that the mechanisms of beta cell tolerance to GAD and IA-2 differ in healthy children.

Swedish children with celiac disease comply well with a gluten-free diet, and most include oats without reporting any adverse effects: a long-term follow-up study.

The only known treatment for celiac disease is a gluten-free diet (GFD), which initially meant abstention from wheat, rye, barley, and oats. Recently, oats free from contamination with wheat have been accepted in the GFD. Yet, reports indicate that all celiac disease patients may not tolerate oats. We hypothesized that celiac children comply well with a GFD and that most have included oats in their diet. A food questionnaire was used to check our patients; 316 questionnaires were returned. Mean time on the GFD was 6.9 years, and 96.8% of the children reported that they were trying to keep a strict GFD. However, accidental transgressions occurred in 263 children (83.2%). In 2 of 3 cases, mistakes took place when the patients were not at home. Symptoms after incidental gluten intake were experienced by 162 (61.6%) patients, mostly (87.5%) from the gastrointestinal tract. Small amounts of gluten (<4 g) caused symptoms in 38% of the cases, and 68% reported symptoms during the first 3 hours after gluten consumption. Oats were included in the diet of 89.4% of the children for a mean of 3.4 years. Most (81.9%) ate purified oats, and 45.3% consumed oats less than once a week. Among those who did not consume oats, only 5.9% refrained because of symptoms. General compliance with the GFD was good. Only the duration of the GFD appeared to influence adherence to the diet. Most patients did not report adverse effects after long-term consumption of oats.