INTRODUCTION:Gliadin proteins play a key role in the pathogenesis of celiac disease; however, as a screen for celiac disease, anti-gliadin antibody testing has been replaced by the more sensitive and specific serological assays for transglutaminase autoantibodies (TGAA). A new generation of anti-gliadin antibody assays has been developed to detect synthetic, deamidated homologous gliadin peptides (DGP) with high sensitivity and specificity.METHODS:Sera were collected prospectively from children with an increased risk for celiac disease as part of an ongoing study at Denver, and studied for the development of celiac autoimmunity. We investigated the high-performance DGP antibody assay in 50 TGAA-positive children both before the development of celiac autoimmunity and following the institution of a gluten-free diet to determine the relationship of DGP antibodies to TGAA. TGAA were measured by an in-house radioassay.RESULTS:DGP antibodies and TGAA parallel each other over the period of years children were studied. DGP antibodies resolved sooner than TGAA in subjects on a gluten-free diet. DGP antibodies appeared earlier than TGAA in 9 children.CONCLUSIONS:Measuring DGP antibodies may be more useful than TGAA in monitoring children on a gluten-free diet. DGP antibodies can precede the appearance of TGAA in some at-risk children.

OBJECTIVE:Children with type 1 diabetes (T1DM) are at increased risk for celiac disease (CD); however, the benefits of screening for IgA tissue transglutaminase autoantibodies (TG), a marker for CD, are unclear.STUDY DESIGN:We compared 71 screening-identified TG+ with 63 matched TG- children with TIDM. Growth, bone density, and diabetes control measures were obtained.RESULTS:The group was 10 +/- 3 years of age, 46% male, with TIDM for 4 +/- 3 years. Z scores for weight (0.3 +/- 1 vs 0.7 +/- 0.8, P = .024), body mass index (BMI) (0.3 +/- 0.9 vs 0.8 +/- -0.8, P = .005), and midarm circumference (0.3 +/- 1.1 vs 0.6 +/- 0.9, P = .031) were lower in the TG+ group. Bone mineral density and diabetes control measures were similar. When limiting the analysis to the 35 TG+ subjects with biopsy changes of CD, the BMI Z score was lower than the control group (0.4 +/- 0.9 vs 0.7 +/- 0.7, P = .05).CONCLUSIONS:In children with TIDM, screening-identified evidence of CD is associated with altered body composition, but not bone mineral density or diabetes control. Further study is needed to determine the benefit of early diagnosis and treatment of CD in TIDM children.

OBJECTIVE Few studies have assessed the role of specific gastrointestinal infections in celiac disease. We investigated whether increased frequency of rotavirus infection, a common cause of gastrointestinal infection and inflammation, predicts increased risk of celiac disease autoimmunity. METHODS A cohort of 1,931 children from the Denver metropolitan area who carried celiac disease human leukocyte antigen (HLA) risk alleles were followed from infancy for development of celiac disease autoimmunity, defined as positivity at two or more subsequent clinic visits for tissue transglutaminase (tTG) autoantibodies measured using a radioimmunoassay with human recombinant tTG. Blood samples were obtained at ages 9, 15, and 24 months, and annually thereafter. Rotavirus antibodies were assayed using an indirect enzyme immunoassay in serial serum samples from each case and two matched controls. Frequency of infections were estimated by the number of increases (>2 assay coefficient of variation) in rotavirus antibody between clinic visits. RESULTS Fifty-four cases developed celiac disease autoimmunity at a median age of 4.4 yr. Thirty-six had an intestinal biopsy, of which 27 (75%) were positive for celiac disease. Frequent rotavirus infections predicted a higher risk of celiac disease autoimmunity (compared with zero infections, rate ratio 1.94, 95% confidence interval [CI] 0.39–9.56, for one infection and rate ratio 3.76, 95% CI 0.76–18.7, for ≥2 infections, rate ratio for trend per increase in number of infections = 1.94, 95% CI 1.04–3.61, p = 0.037). The result was similar after adjustment for gender, ethnic group, maternal education, breast-feeding, day-care attendance, number of siblings, season of birth, and number of HLA DR3-DQ2 haplotypes. CONCLUSIONS This prospective study provides the first indication that a high frequency of rotavirus infections may increase the risk of celiac disease autoimmunity in childhood in genetically predisposed individuals.

Journal of Pediatric Gastroenterology and NutritionVolume 43, Issue 4 p. E43-E44 North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition Annual Meeting, October 19-22, 2006, Orlando, Florida: Abstracts: POSTER SESSION II, FRIDAY, OCTOBER 20, 2006, 12:15 p.m. - 2:15 p.m.: Intestine/Colon/IBD: 95 SCREENING-IDENTIFIED EVIDENCE OF CELIAC DISEASE IN DIABETIC CHILDREN 1 YEAR OUTCOME Edward Hoffenberg, Edward Hoffenberg Pediatrics, The Childrens Hospital and UCDHSC, Denver, COSearch for more papers by this authorJill H. Simmons, Jill H. Simmons Barbara Davis Center, UCDHSC, Aurora, COSearch for more papers by this authorGeorgeanna J. Klingensmith, Georgeanna J. Klingensmith Barbara Davis Center, UCDHSC, Aurora, COSearch for more papers by this authorKim McFann, Kim McFann Barbara Davis Center, UCDHSC, Aurora, COSearch for more papers by this authorLisa M. Emery, Lisa M. Emery Barbara Davis Center, UCDHSC, Aurora, COSearch for more papers by this authorMarian Rewers, Marian Rewers Barbara Davis Center, UCDHSC, Aurora, COSearch for more papers by this authorIman Taki, Iman Taki Barbara Davis Center, UCDHSC, Aurora, COSearch for more papers by this authorSharon Vanyi, Sharon Vanyi Barbara Davis Center, UCDHSC, Aurora, COSearch for more papers by this authorEdwin Liu, Edwin Liu Pediatrics, The Childrens Hospital and UCDHSC, Denver, COSearch for more papers by this author Edward Hoffenberg, Edward Hoffenberg Pediatrics, The Childrens Hospital and UCDHSC, Denver, COSearch for more papers by this authorJill H. Simmons, Jill H. Simmons Barbara Davis Center, UCDHSC, Aurora, COSearch for more papers by this authorGeorgeanna J. Klingensmith, Georgeanna J. Klingensmith Barbara Davis Center, UCDHSC, Aurora, COSearch for more papers by this authorKim McFann, Kim McFann Barbara Davis Center, UCDHSC, Aurora, COSearch for more papers by this authorLisa M. Emery, Lisa M. Emery Barbara Davis Center, UCDHSC, Aurora, COSearch for more papers by this authorMarian Rewers, Marian Rewers Barbara Davis Center, UCDHSC, Aurora, COSearch for more papers by this authorIman Taki, Iman Taki Barbara Davis Center, UCDHSC, Aurora, COSearch for more papers by this authorSharon Vanyi, Sharon Vanyi Barbara Davis Center, UCDHSC, Aurora, COSearch for more papers by this authorEdwin Liu, Edwin Liu Pediatrics, The Childrens Hospital and UCDHSC, Denver, COSearch for more papers by this author First published: 01 October 2006 https://doi.org/10.1002/j.1536-4801.2006.tb13838.xRead the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume43, Issue4October 2006Pages E43-E44 RelatedInformation

Approximately 50% of the genetic risk for type 1 diabetes is attributable to the HLA region. We evaluated associations between candidate genes outside the HLA region-INS, cytotoxic T-lymphocyte-associated antigen (CTLA)-4, interleukin (IL)-4, IL-4R, and IL-13 and islet autoimmunity among children participating in the Diabetes Autoimmunity Study in the Young (DAISY). Children with persistent islet autoantibody positivity (n = 102, 38 of whom have already developed diabetes) and control subjects (n = 198) were genotyped for single nucleotide polymorphisms (SNPs) in the candidate genes. The INS-23Hph1 polymorphism was significantly associated with both type 1 diabetes (OR = 0.30; 95% CI 0.13-0.69) and persistent islet autoimmunity but in the latter, only in children with the HLA-DR3/4 genotype (0.40; 0.18-0.89). CTLA-4 promoter SNP was significantly associated with type 1 diabetes (3.52; 1.22-10.17) but not with persistent islet autoimmunity. Several SNPs in the IL-4 regulatory pathway appeared to have a predisposing effect for type 1 diabetes. Associations were found between both IL-4R haplotypes and IL-4-IL-13 haplotypes and persistent islet autoimmunity and type 1 diabetes. This study confirms the association between the INS and CTLA-4 loci and type 1 diabetes. Genes involved in the IL-4 regulatory pathway (IL-4, IL-4R, IL-13) may confer susceptibility or protection to type 1 diabetes depending on individual SNPs or specific haplotypes.

Objective: Certain human leukocyte antigen (HLA)-DR,DQ genotypes have been associated with type 1 diabetes mellitus (T1DM) risk, although it is unknown whether the association is due to alleles, haplotypes, genotypes, the formation of heterodimers, or all of the above. To characterize the role of the HLA-DR,DQ genotype and ethnicity on the onset age of T1DM, we analyzed these factors in patients with T1DM and the general population.Methods: One thousand three hundred twenty-two well-characterized patients with T1DM were compared with 3339 children from the general population of Denver, Colorado, USA. Because of the extensive available data across age and ethnic groups, this study population is unique.Results: The HLA-DR3/4,DQB1*0302, DRX/4,DQB1*0302 (where X = 1, 4, 8, and 9), and HLA-DR3/3 genotypes were associated with T1DM, supporting previous research. Additionally, the DR3/9 genotype showed a positive association with T1DM, which has not previously been described in Caucasian populations. The HLA-DR3/4*0302 genotype was most strongly associated with T1DM in diabetic individuals with the youngest onset age. Genotype frequencies were similar between Hispanics and non-Hispanic whites, except for the DR3/3 genotype, which was more likely to be found in non-Hispanic whites.Conclusions: These results indicate that there are multiple alleles and genotypes associated with T1DM and that the risk associated with different genetic markers depends on the age of disease onset, suggesting that some markers may be involved in more rapid disease progression.

OBJECTIVEAt-risk groups commonly undergo screening for autoantibodies associated with celiac disease (CD). However, the clinical significance of a positive test remains uncertain. The objective of this study was to evaluate growth and clinical features of children who test positive for an autoantibody associated with CD.METHODSA case-control study of Denver area healthy infants and young children with and without CD autoantibodies was conducted. A cohort of HLA-characterized children were followed prospectively since birth for the development of immunoglobulin A antitissue transglutaminase autoantibodies (TG). Clinical evaluation, questionnaire, blood draw, and small bowel biopsy were performed. Growth and nutrition and frequency of positive responses were measured.RESULTSCompared with 100 age- and gender-matched TG-negative controls, 18 TG-positive children, 5.5 +/- 0.5 years of age, had a greater number of symptoms and lower z scores for weight-for-height and for body mass index. Responses that were independently associated with TG-positive status were irritability/lethargy, abdominal distention/gas, and difficulty with weight gain.CONCLUSIONSScreening-identified TG-positive children demonstrate mild alterations in growth and nutrition and report more symptoms than control subjects. Additional study is needed on the benefit and risk of identifying CD in at-risk groups.

Journal of Pediatric Gastroenterology and NutritionVolume 39, Issue S1 p. S209-S209 ABSTRACTS: Poster Session Abstracts P0403 EVALUATION OF LIVER FUNCTION TESTS IN SCREENING-IDENTIFIED CHILDREN WITH CELIAC DISEASE L. M. Emery MSPH, L. M. Emery MSPH Preventive Medicine and Biometrics, University of Colorado Health Sciences Center, Denver, United StatesSearch for more papers by this authorE. J. Hoffenberg MD, E. J. Hoffenberg MD Pediatrics, Denver, United StatesSearch for more papers by this authorI. Taki BS, I. Taki BS Preventive Medicine and Biometrics, University of Colorado Health Sciences Center, Denver, United StatesSearch for more papers by this authorR. J. Sokol MD, R. J. Sokol MD Pediatrics, Denver, United StatesSearch for more papers by this authorJ. E. Haas MD, J. E. Haas MD Pathology, The Children’s Hospital, Denver, United StatesSearch for more papers by this authorM. Rewers MD, PhD, M. Rewers MD, PhD Pediatrics, Barbara Davis Center for Childhood Diabetes, Denver, United StatesSearch for more papers by this author L. M. Emery MSPH, L. M. Emery MSPH Preventive Medicine and Biometrics, University of Colorado Health Sciences Center, Denver, United StatesSearch for more papers by this authorE. J. Hoffenberg MD, E. J. Hoffenberg MD Pediatrics, Denver, United StatesSearch for more papers by this authorI. Taki BS, I. Taki BS Preventive Medicine and Biometrics, University of Colorado Health Sciences Center, Denver, United StatesSearch for more papers by this authorR. J. Sokol MD, R. J. Sokol MD Pediatrics, Denver, United StatesSearch for more papers by this authorJ. E. Haas MD, J. E. Haas MD Pathology, The Children’s Hospital, Denver, United StatesSearch for more papers by this authorM. Rewers MD, PhD, M. Rewers MD, PhD Pediatrics, Barbara Davis Center for Childhood Diabetes, Denver, United StatesSearch for more papers by this author First published: 01 June 2004 https://doi.org/10.1002/j.1536-4801.2004.tb12833.x Submitted by: [email protected] Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume39, IssueS1June 2004Pages S209-S209 RelatedInformation

Approximately 50% of the genetic risk for type 1 diabe- tes is attributable to the HLA region. We evaluated associations between candidate genes outside the HLA region-INS, cytotoxic T-lymphocyte-associated antigen (CTLA)-4, interleukin (IL)-4, IL-4R, and IL-13 and islet autoimmunity among children participating in the Dia- betes Autoimmunity Study in the Young (DAISY). Chil- dren with persistent islet autoantibody positivity (n 102, 38 of whom have already developed diabetes) and control subjects (n 198) were genotyped for single nucleotide polymorphisms (SNPs) in the candidate genes. The INS-23Hph1 polymorphism was significantly associated with both type 1 diabetes (OR 0.30; 95% CI 0.13- 0.69) and persistent islet autoimmunity but in the latter, only in children with the HLA-DR3/4 genotype (0.40; 0.18 - 0.89). CTLA-4 promoter SNP was signifi- cantly associated with type 1 diabetes (3.52; 1.22- 10.17) but not with persistent islet autoimmunity. Several SNPs in the IL-4 regulatory pathway appeared to have a predisposing effect for type 1 diabetes. Asso- ciations were found between both IL-4R haplotypes and IL-4 -IL-13 haplotypes and persistent islet autoimmu- nity and type 1 diabetes. This study confirms the asso- ciation between the INS and CTLA-4 loci and type 1 diabetes. Genes involved in the IL-4 regulatory pathway (IL-4, IL-4R, IL-13) may confer susceptibility or protec- tion to type 1 diabetes depending on individual SNPs or specific haplotypes. Diabetes 54:2482-2486, 2005