CD25 deficiency: A new conformational mutation prevents the receptor expression on cell surface.

CD25 deficiency is a very rare autosomal recessive disorder that shows a clinical phenotype highly overlapping IPEX syndrome with an increased susceptibility to viral, bacterial, and fungal infections. It is due to mutations in the IL2Rα gene that codes for the α subunit of the IL2 receptor complex. Here we report the characterization of a novel IL2Rα gene mutation leading to a severe protein conformational alteration that abrogates its cell surface expression in a child presenting with early-onset IPEX-like disorder. Cytofluorimetric analysis revealed the total absence of CD25 cell surface expression and addressed IL2Rα molecular investigation. The early clinical and molecular diagnosis of CD25 deficiency in this patient promptly led to hematopoietic stem cell transplantation (HSCT), allowing complete resolution of the symptoms and definitive cure of the disease.

Efficacy of adalimumab as second-line therapy in a pediatric cohort of Crohn's disease patients who failed infliximab therapy: the Italian Society of Pediatric Gastroenterology, Hepatology, and Nutrition experience.

BACKGROUND: Adalimumab (Ada) treatment is an available option for pediatric Crohn's disease (CD) and the published experience as rescue therapy is limited. OBJECTIVES: We investigated Ada efficacy in a retrospective, pediatric CD cohort who had failed previous infliximab treatment, with a minimum follow-up of 6 months. METHODS: In this multicenter study, data on demographics, clinical activity, growth, laboratory values (CRP) and adverse events were collected from CD patients during follow-up. Clinical remission (CR) and response were defined with Pediatric CD Activity Index (PCDAI) score ≤10 and a decrease in PCDAI score of ≥12.5 from baseline, respectively. RESULTS: A total of 44 patients were consecutively recruited (mean age 14.8 years): 34 of 44 (77%) had active disease (mean PCDAI score 24.5) at the time of Ada administration, with a mean disease duration of 3.4 (range 0.3-11.2) years. At 6, 12, and 18 months, out of the total of the enrolled population, CR rates were 55%, 78%, and 52%, respectively, with a significant decrease in PCDAI scores (P<0.01) and mean CRP values (mean CRP 5.7 and 2.4 mL/dL, respectively; P<0.01) at the end of follow-up. Steroid-free remission rates, considered as the total number of patients in CR who were not using steroids at the end of this study, were 93%, 95%, and 96% in 44 patients at 6, 12, and 18 months, respectively. No significant differences in growth parameters were detected. In univariate analysis of variables related to Ada efficacy, we found that only a disease duration >2 years was negatively correlated with final PCDAI score (P<0.01). Two serious adverse events were recorded: 1 meningitis and 1 medulloblastoma. CONCLUSION: Our data confirm Ada efficacy in pediatric patients as second-line biological therapy after infliximab failure. Longer-term prospective data are warranted to define general effectiveness and safety in pediatric CD patients.

Diagnostic Yield of Next-generation Sequencing in Very Early-onset Inflammatory Bowel Diseases: A Multicentre Study.

BACKGROUND AND AIMS: An expanding number of monogenic defects have been identified as causative of severe forms of very early-onset inflammatory bowel diseases [VEO-IBD]. The present study aimed at defining how next-generation sequencing [NGS] methods can be used to improve identification of known molecular diagnosis and to adapt treatment. METHODS: A total of 207 children were recruited in 45 paediatric centres through an international collaborative network [ESPGHAN GENIUS working group] with a clinical presentation of severe VEO-IBD [n = 185] or an anamnesis suggestive of a monogenic disorder [n = 22]. Patients were divided at inclusion into three phenotypic subsets: predominantly small bowel inflammation, colitis with perianal lesions, and colitis only. Methods to obtain molecular diagnosis included functional tests followed by specific Sanger sequencing, custom-made targeted NGS, and in selected cases whole exome sequencing [WES] of parents-child trios. Genetic findings were validated clinically and/or functionally. RESULTS: Molecular diagnosis was achieved in 66/207 children [32%]: 61% with small bowel inflammation, 39% with colitis and perianal lesions, and 18% with colitis only. Targeted NGS pinpointed gene mutations causative of atypical presentations, and identified large exonic copy number variations previously missed by WES. CONCLUSIONS: Our results lead us to propose an optimised diagnostic strategy to identify known monogenic causes of severe IBD.

Treating children with inflammatory bowel disease: Current and new perspectives.

Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gut characterised by alternating periods of remission and relapse. Whilst the mechanism underlying this disease is yet to be fully understood, old and newer generation treatments can only target selected pathways of this complex inflammatory process. This narrative review aims to provide an update on the most recent advances in treatment of paediatric IBD. A MEDLINE search was conducted using "paediatric inflammatory bowel disease", "paediatric Crohn's disease", "paediatric ulcerative colitis", "treatment", "therapy", "immunosuppressant", "biologic", "monitoring" and "biomarkers" as key words. Clinical trials, systematic reviews, and meta-analyses published between 2014 and 2016 were selected. Studies referring to earlier periods were also considered in case the data was relevant to our scope. Major advances have been achieved in monitoring the individual metabolism, toxicity and response to relevant medications in IBD including thiopurines and biologics. New biologics acting on novel mechanisms such as selective interference with lymphocyte trafficking are emerging treatment options. Current research is investing in the development of reliable prognostic biomarkers, aiming to move towards personalised treatments targeted to individual patients.

Assessing pediatric ileocolonic Crohn's disease activity based on global MR enterography scores.

OBJECTIVES: This study was aimed at correlating a magnetic resonance index of activity (MaRIA) and a magnetic resonance enterography global score (MEGS) with activity indexes in a paediatric population with Crohn's disease (CD). METHODS: This retrospective study included 32 paediatric patients (median age 14.5 years, 18 male) with proven CD who underwent magnetic resonance enterography (MRE). A correlation analysis was performed on the MRE-based scores, the simplified endoscopic score for CD (SES-CD), the paediatric Crohn's disease activity index (PCDAI), and C-reactive protein (CRP) levels. Based on PCDAI, comparison of both global MaRIA and MEGS was made between patients with mild and moderate/severe disease activity. RESULTS: Global MaRIA correlated with SES-CD (r = 0.70, p = 0.001) and PCDAI (r = 0.42, p = 0.016). MEGS correlated with PCDAI (r = 0.46, p = 0.007) and CRP levels (r = 0.35, p = 0.046). MEGS differed significantly (p = 0.027) between patients grouped by clinical disease severity. CONCLUSIONS: MRE-based global scores correlated with clinical indexes of CD activity. Therefore, they represent a potential useful tool to predict CD activity and severity, as well as a possible promising alternative to endoscopy, to monitor paediatric patients with CD during their follow-up. KEY POINTS: • MRE is widely used to for accurate assessment of CD. • Global MaRIA and MEGS have been suggested as indicators of CD activity. • Paediatric studies comparing MRE-based global scores with clinical CD activity are lacking. • Such scores can serve as predictors of CD activity/severity in paediatric patients. • MRE offers an alternative to clinical score/endoscopy for paediatric CD monitoring.

Clinical course and outcomes of diagnosing Inflammatory Bowel Disease in children 10 years and under: retrospective cohort study from two tertiary centres in the United Kingdom and in Italy.

BACKGROUND: Most children with Inflammatory Bowel Disease (IBD) are diagnosed between 11 and 16 years of age, commonly presenting with features of typical IBD. Children with onset of gut inflammation under 5 years of age often have a different underlying pathophysiology, one that is genetically and phenotypically distinct from other children with IBD. We therefore set out to assess whether children diagnosed after the age of 5 years, but before the age of 11, have a different clinical presentation and outcome when compared to those presenting later. METHODS: Retrospective cohort study conducted at two European Paediatric Gastroenterology Units. Two cohorts of children with IBD (total number = 160) were compared: 80 children diagnosed between 5 and 10 years (Group A), versus 80 children diagnosed between 11 and 16 (Group B). Statistical analysis included multiple logistic regression. RESULTS: Group A presented with a greater disease activity (p = 0.05 for Crohn's disease (CD), p = 0.03 for Ulcerative Colitis (UC); Odds Ratio 1.09, 95 % Confidence Interval: 1.02-1.1), and disease extent (L2 location more frequent amongst Group A children with CD (p = 0.05)). No significant differences were observed between age groups in terms of gastro-intestinal and extra-intestinal signs and symptoms at disease presentation, nor was there a difference in the number of hospitalisations due to relapsing IBD during follow-up. However, children in Group A were treated earlier with immunosuppressants and had more frequent endoscopic assessments. CONCLUSION: While clinicians feel children between 5 and 10 years of age have a more severe disease course than adolescents, our analysis also suggests a greater disease burden in this age group. Nevertheless, randomized trials to document longer-term clinical outcomes are urgently needed, in order to address the question whether a younger age at disease onset should prompt per se a more "aggressive" treatment. We speculate that non-clinical factors (e.g. genetics, epigenetics) may have more potential to predict longer term outcome than simple clinical measures such as age at diagnosis.

Italian survey on non-steroidal anti-inflammatory drugs and gastrointestinal bleeding in children.

AIM: To investigate gastrointestinal complications associated with non-steroidal anti-inflammatory drug (NSAIDs) use in children. METHODS: A retrospective, multicenter study was conducted between January 2005 and January 2013, with the participation of 8 Italian pediatric gastroenterology centers. We collected all the cases of patients who refer to emergency room for suspected gastrointestinal bleeding following NSAIDs consumption, and underwent endoscopic evaluation. Previous medical history, associated risk factors, symptoms and signs at presentation, diagnostic procedures, severity of bleeding and management of gastrointestinal bleeding were collected. In addition, data regarding type of drug used, indication, dose, duration of treatment and prescriber (physician or self-medication) were examined. RESULTS: Fifty-one patients, including 34 males, were enrolled (median age: 7.8 years). Ibuprofen was the most used NSAID [35/51 patients (68.6%)]. Pain was the most frequent indication for NSAIDs use [29/51 patients (56.9%)]. Seven patients had positive family history of Helicobacter pylori (H. pylori) infection or peptic ulcer, and 12 had associated comorbidities. Twenty-four (47%) out of 51 patients used medication inappropriately. Hematemesis was the most frequent symptom (33.3%). Upper gastrointestinal endoscopy revealed gastric lesions in 32/51 (62%) patients, duodenal lesions in 17 (33%) and esophageal lesions in 8 (15%). In 10/51 (19.6%) patients, a diagnosis of H. pylori gastritis was made. Forty-eight (94%) patients underwent medical therapy, with spontaneous bleeding resolution, while in 3/51 (6%) patients, an endoscopic hemostasis was needed. CONCLUSION: The data collected in this study confirms that adverse events with the involvement of the gastrointestinal tract secondary to NSAID use are also common in children.

Transition of gastroenterological patients from paediatric to adult care: A position statement by the Italian Societies of Gastroenterology.

In 2013, four Italian Gastroenterological Societies (the Italian Society of Paediatric Gastroenterology, Hepatology and Nutrition, the Italian Society of Hospital Gastroenterologists and Endoscopists, the Italian Society of Endoscopy, and the Italian Society of Gastroenterology) formed a joint panel of experts with the aim of preparing an official statement on transition medicine in Gastroenterology. The transition of adolescents from paediatric to adult care is a crucial moment in managing chronic diseases such as celiac disease, inflammatory bowel disease, liver disease and liver transplantation. Improved medical treatment and availability of new drugs and surgical techniques have improved the prognosis of many paediatric disorders, prolonging survival, thus making the transition to adulthood possible and necessary. An inappropriate transition or the incomplete transmission of data from the paediatrician to the adult Gastroenterologist can dramatically decrease compliance to treatment and prognosis of a young patient, particularly in the case of severe disorders. For these reasons, the Italian gastroenterological societies decided to develop an official shared transition protocol. The resulting document discusses the factors influencing the transition process and highlights the main points to accomplish to optimize compliance and prognosis of gastroenterological patients during the difficult transition from childhood to adolescence and adulthood.

TNFA Haplotype Genetic Testing Improves HLA in Estimating the Risk of Celiac Disease in Children.

BACKGROUND: TNF-α and IFN-γ play a role in the development of mucosal damage in celiac disease (CD). Polymorphisms of TNFA and IFNG genes, as well as of the TNFRSF1A gene, encoding the TNF-α receptor 1, might underlie different inter-individual disease susceptibility over a common HLA risk background. The aims of this study were to ascertain whether five SNPs in the TNFA promoter (-1031T>C,-857C>T,-376G>A,-308G>A,-238G>A), sequence variants of the TNFRSF1A gene and IFNG +874A>T polymorphism are associated with CD in a HLA independent manner. METHODS: 511 children (244 CD, 267 controls) were genotyped for HLA, TNFA and INFG (Real Time PCR). TNFRSF1A variants were studied (DHPLC and sequence). RESULTS: Only the rare TNFA-1031C (OR=0.65, 95% CI:0.44-0.95), -857T (OR=0.42, 95% CI:0.27-0.65), -376A (OR=2.25, 95% CI:1.12-4.51) and -308A (OR=4.76, 95% CI:3.12-7.26) alleles were significantly associated with CD. One TNFRSF1A variant was identified (c.625+10A>G, rs1800693), but not associated with CD. The CD-correlated TNFA SNPs resulted in six haplotypes. Two haplotypes were control-associated (CCGG and TTGG) and three were CD-associated (CCAG, TCGA and CCGA). The seventeen inferred haplotype combinations were grouped (A to E) based on their frequencies among CD. Binary logistic regression analysis documented a strong association between CD and HLA (OR for intermediate risk haplotypes=178; 95% CI:24-1317; OR for high risk haplotypes=2752; 95% CI:287-26387), but also an HLA-independent correlation between CD and TNFA haplotype combination groups. The CD risk for patients carrying an intermediate risk HLA haplotype could be sub-stratified by TNFA haplotype combinations. CONCLUSION: TNFA promoter haplotypes associate with CD independently from HLA. We suggest that their evaluation might enhance the accuracy in estimating the CD genetic risk.

The multidisciplinary health care team in the management of stenosis in Crohn's disease.

BACKGROUND: Stricture formation is a common complication of Crohn's disease (CD), occurring in approximately one-third of all patients with this condition. Our aim was to summarize the available epidemiology data on strictures in patients with CD, to outline the principal evidence on diagnostic imaging, and to provide an overview of the current knowledge on treatment strategies, including surgical and endoscopic options. Overall, the unifying theme of this narrative review is the multidisciplinary approach in the clinical management of patients with stricturing CD. METHODS: A Medline search was performed, using "Inflammatory Bowel Disease", "stricture", "Crohn's Disease", "Ulcerative Colitis", "endoscopic balloon dilatation" and "strictureplasty" as keywords. A selection of clinical cohort studies and systematic reviews were reviewed. RESULTS: Strictures in CD are described as either inflammatory or fibrotic. They can occur de novo, at sites of bowel anastomosis or in the ileal pouch. CD-related strictures generally show a poor response to medical therapies, and surgical bowel resection or surgical strictureplasty are often required. Over the last three decades, the potential role of endoscopic balloon dilatation has grown in importance, and nowadays this technique is a valid option, complementary to surgery. CONCLUSION: Patients with stricturing CD require complex clinical management, which benefits from a multidisciplinary approach: gastroenterologists, pediatricians, radiologists, surgeons, specialist nurses, and dieticians are among the health care providers involved in supporting these patients throughout diagnosis, prevention of complications, and treatment.

Natural history of pancreatic involvement in paediatric inflammatory bowel disease.

BACKGROUND: Few case reports describe the clinical features of pancreatic involvement in inflammatory bowel disease. AIM: To investigate prevalence and disease course of inflammatory bowel disease children with pancreatitis and with exclusive hyperamylasemia and hyperlipasemia. METHODS: We used a web-registry to retrospectively identify paediatric inflammatory bowel disease patients with hyperamylasemia and hyperlipasemia. Participants were re-evaluated at 6 months and 1 year. RESULTS: From a total of 649 paediatric patients, we found 27 with hyperamylasemia and hyperlipasemia (4.1%). Eleven patients (1.6%) fulfilled diagnostic criteria for acute pancreatitis. Female gender was significantly associated with acute pancreatitis (p=0.04). Twenty-five children (92.5%) had colonic disease. At 6 months 1/11 children with acute pancreatitis (9%) showed acute recurrent pancreatitis, while 1 patient (9%) had persistent hyperamylasemia and hyperlipasemia. At 12 months, 1 patient showed chronic pancreatitis (9.1%). Of the 16 children with exclusive hyperamylasemia and hyperlipasemia, 4 developed acute pancreatitis (25%), while 1 patient (6.2%) still presented exclusive hyperamylasemia and hyperlipasemia at 6 months. At 12 months, 11/16 patients (68.7%) reached a remission of pancreatic involvement, whereas 5 remaining patients (32.3%) had persistent hyperamylasemia and hyperlipasemia. CONCLUSIONS: In inflammatory bowel disease children, acute pancreatitis is more common in colonic disease and in female gender. Pancreatic function should be monitored, considering that pancreatic damage may evolve.

Crohn's disease and growth deficiency in children and adolescents.

Nutritional concerns, linear growth deficiency, and delayed puberty are currently detected in up to 85% of patients with Crohn's disease (CD) diagnosed at childhood. To provide advice on how to assess and manage nutritional concerns in these patients, a Medline search was conducted using "pediatric inflammatory bowel disease", "pediatric Crohn's disease", "linear growth", "pubertal growth", "bone health", and "vitamin D" as key words. Clinical trials, systematic reviews, and meta-analyses published between 2008 and 2013 were selected to produce this narrative review. Studies referring to earlier periods were also considered if the data was relevant to our review. Although current treatment strategies for CD that include anti-tumor necrosis factor-α therapy have been shown to improve patients' growth rate, linear growth deficiencies are still common. In pediatric CD patients, prolonged diagnostic delay, high initial activity index, and stricturing/penetrating type of behavior may cause growth deficiencies (in weight and height) and delayed puberty, with several studies reporting that these patients may not reach an optimal bone mass. Glucocorticoids and inflammation inhibit bone formation, though their impact on skeletal modeling remains unclear. Long-term control of active inflammation and an adequate intake of nutrients are both fundamental in promoting normal puberty. Recent evidence suggests that recombinant growth factor therapy is effective in improving short-term linear growth in selected patients, but is of limited benefit for ameliorating mucosal disease and reducing clinical disease activity. The authors conclude that an intense initial treatment (taking a "top-down" approach, with the early introduction of immunomodulatory treatment) may be justified to induce and maintain remission so that the growth of children with CD can catch up, ideally before puberty. Exclusive enteral nutrition has a key role in inducing remission and improving patients' nutritional status.

Introduction of gluten, HLA status, and the risk of celiac disease in children.

BACKGROUND: The relationship between the risk of celiac disease and both the age at which gluten is introduced to a child's diet and a child's early dietary pattern is unclear. METHODS: We randomly assigned 832 newborns who had a first-degree relative with celiac disease to the introduction of dietary gluten at 6 months (group A) or 12 months (group B). The HLA genotype was determined at 15 months of age, and serologic screening for celiac disease was evaluated at 15, 24, and 36 months and at 5, 8, and 10 years. Patients with positive serologic findings underwent intestinal biopsies. The primary outcome was the prevalence of celiac disease autoimmunity and of overt celiac disease among the children at 5 years of age. RESULTS: Of the 707 participants who remained in the trial at 36 months, 553 had a standard-risk or high-risk HLA genotype and completed the study. At 2 years of age, significantly higher proportions of children in group A than in group B had celiac disease autoimmunity (16% vs. 7%, P=0.002) and overt celiac disease (12% vs. 5%, P=0.01). At 5 years of age, the between-group differences were no longer significant for autoimmunity (21% in group A and 20% in group B, P=0.59) or overt disease (16% and 16%, P=0.78 by the log-rank test). At 10 years, the risk of celiac disease autoimmunity was far higher among children with high-risk HLA than among those with standard-risk HLA (38% vs. 19%, P=0.001), as was the risk of overt celiac disease (26% vs. 16%, P=0.05). Other variables, including breast-feeding, were not associated with the development of celiac disease. CONCLUSIONS: Neither the delayed introduction of gluten nor breast-feeding modified the risk of celiac disease among at-risk infants, although the later introduction of gluten was associated with a delayed onset of disease. A high-risk HLA genotype was an important predictor of disease. (Funded by the Fondazione Celiachia of the Italian Society for Celiac Disease; CELIPREV ClinicalTrials.gov number, NCT00639444.).

Phenotype and disease course of early-onset pediatric inflammatory bowel disease.

BACKGROUND: Early-onset (EO) pediatric inflammatory bowel diseases (IBD) seem to be more extensive than those with a later onset. To test this hypothesis, we examined the phenotype and disease course of patients with IBD diagnosis at 0 to 5 years, compared with the ranges 6 to 11 and 12 to 18 years. METHODS: Anatomic locations and behaviors were assessed according to Paris classification in 506 consecutive patients: 224 Crohn's disease, 245 ulcerative colitis, and 37 IBD-unclassified. RESULTS: Eleven percent of patients were in the range 0 to 5 years, 39% in 6 to 11 years, and 50% in 12 to 18 years. Ulcerative colitis was the most frequent diagnosis in EO-IBD and in 6- to 11-year-old group, whereas Crohn's disease was predominant in older children. A classification as IBD-unclassified was more common in the range 0 to 5 years compared with the other groups (P < 0.005). EO Crohn's disease showed a more frequent isolated colonic (P < 0.005) and upper gastrointestinal involvement than later-onset disease. Sixty-two percent of the patients in the 0 to 5 years range had pancolonic ulcerative colitis, compared with 38% of 6 to 11 years (P = 0.02) and 31% of 12-18 years (P = 0.002) range. No statistical difference for family history for IBD was found in the 3-year age groups. Therapies at the diagnosis were similar for all children. However, at latest follow-up, a significantly higher proportion of younger children were under steroids compared with older groups (P < 0.05). Surgical risk did not differ according to age. CONCLUSIONS: EO-IBD exhibits an extensive phenotype and benefit from aggressive treatment strategies, although surgical risk is similar to later-onset disease. A family history for IBD is not common in EO disease.

Early-life factors associated with pediatric functional constipation.

OBJECTIVE: This multicenter prospective study aimed to establish possible risk factors for functional constipation (FC) in the first year of life. METHODS: At the infant's age of 3, 6, and 12 months, parents of all included infants completed 2 questionnaires: one about the presence of FC and the other screened the possible risk factors for FC. Parents of 465 infants completed the questionnaires at 3 and 6 months and of 402 infants at 12 months of life. RESULTS: According to the Rome III criteria, FC was found in 11.6% of the infants at 3 months, in 13.7% at 6 months, and in 10.7% at 12 months after birth. Family history of atopy was present in 38.8% and 45.3% of infants with constipation at 3 and 6 months (P = 0.04 and P = 0.02, respectively), but no significant association was found at 12 months (P = 0.80). Breast-feeding was significantly related to a normal evacuation pattern at 3 months (P = 0.05), but not at 6 and 12 months (P = 0.12 and P = 0.9, respectively). Acetaminophen and female sex appeared to be risk factors for FC at 12 months. After the adjustment for all analyzed variables, FC in infants was significantly associated with the use of acetaminophen (odds ratio 6.98, 95% confidence interval 0.82-13.50). CONCLUSIONS: Our results confirmed that breast-feeding is a protective factor for FC in the first 3 months of life and that the female sex is at risk to have FC. We found that the use of acetaminophen was associated with a higher incidence of FC in the first year of life.

Phenotypic characterization of very early-onset IBD due to mutations in the IL10, IL10 receptor alpha or beta gene: a survey of the Genius Working Group.

OBJECTIVE: Early-onset inflammatory bowel disease starting within the first months of life could be due to a particular genetic defect. We set up the GENetically determined ImmUne-mediated enteropathieS (GENIUS) network and collected infants with a proven defect of the IL10 axis for accurate phenotyping of disease presentation and evolution. DESIGN: Ten patients with early-onset inflammatory bowel disease with confirmed mutations in IL10, IL10RA, or IL10RB genes were characterized on clinical, endoscopic-histological, immunobiological, and radiological findings. Functional assays to confirm defective responses to IL10 were performed on peripheral blood mononuclear cells. RESULTS: A functional defect in IL10 signaling was confirmed in all IL10R patients tested. Disease started with severe diarrhea within the first 12 weeks in all patients. All infants showed Crohn's disease-like ulcerations limited to the colon with marked perianal inflammation (fissures, abscess, and fistula); disease progression to the small bowel occurred in only 1 patient. Four of the 10 patients had granulomata on histology, and all patients showed Crohn's disease-like mesenteric infiltration on imaging. Disease pattern was indistinguishable between IL10R alpha or beta chain or IL10 defects; autoimmunity was not observed. Mutations in IL10 were more frequently associated with bacterial and viral infections. Patients responded partially to treatment with steroids or anti-tumor necrosis factor drugs, whereas hematopoietic stem cell transplantation proved efficacious. CONCLUSION: The importance of the IL10 pathway within the colonic mucosa is highlighted by the development of severe colitis within a few weeks in infants with mutations in IL10, IL10RA, or IL10RB. Immunosuppression failed to correct the defect in this pathway, which seems to be a key to controlling inflammation in the colon.

Chemiluminescence and ELISA-based serum assays for diagnosing and monitoring celiac disease in children: a comparative study.

BACKGROUND: Anti-transglutaminase (tTG) or anti-deamidated gliadin peptides (DGP) serum determination is the first step in diagnosing celiac disease (CD). Our aims were to: compare the performance of novel chemiluminescent tool in the detection of tTG and DGP (Q-Flash®, Inova) with that of the established ELISA (Q-Lite®, Inova) methods; identify the more reliable index for making a sound diagnosis and monitoring therapy. METHODS: Using Q-Flash® and Q-Lite®, IgA and IgG class tTG and DGP were measured in the sera of 155 CD pediatric patients and 166 healthy age-matched controls. Forty-two of the patients had a follow-up one year after starting gluten free diet (GFD). RESULTS: Q-Flash® IgA tTG, the more accurate (intra-assay CV for low, intermediate and high values: 2.2%, 1.6%, and 1.1%; inter-assay CV: 2.8%, 4%, and 3%), sensitive (96.1%) and specific (97%) test for diagnosing CD, was the only variable to be significantly correlated with CD at binary logistic regression analysis (r=0.263, p<0.0001, Exp(B)=1.0506, 95% CI=1.0286-1.0731). Q-Flash® IgA tTG or DGP screen were more accurate than Q-Lite® IgA tTG in monitoring CD patients on GFD (p=0.003). CONCLUSION: Q- Flash® IgA tTG measurement is an extremely precise, sensitive and specific index for not only diagnosing CD, but also monitoring therapy.