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  1. Article ; Online: Associations of dietary patterns between age 9 and 24 months with risk of celiac disease autoimmunity and celiac disease among children at increased risk.

    Hård Af Segerstad, Elin M / Mramba, Lazarus K / Liu, Xiang / Uusitalo, Ulla / Yang, Jimin / Norris, Jill / Virtanen, Suvi M / Liu, Edwin / Kurppa, Kalle / Koletzko, Sibylle / Ziegler, Annette G / Toppari, Jorma / Rewers, Marian / Akolkar, Beena / Krischer, Jeffrey P / Aronsson, Carin Andrén / Agardh, Daniel

    The American journal of clinical nutrition

    2023  Volume 118, Issue 6, Page(s) 1099–1105

    Abstract: Background: Higher gluten intake in childhood is associated with increased incidence of celiac disease autoimmunity (CDA) and celiac disease. It remains to be studied whether different dietary patterns independent of gluten intake contribute to the ... ...

    Abstract Background: Higher gluten intake in childhood is associated with increased incidence of celiac disease autoimmunity (CDA) and celiac disease. It remains to be studied whether different dietary patterns independent of gluten intake contribute to the incidence.
    Objectives: This study aimed to explore associations of dietary patterns by age 2 y with risk of CDA and celiac disease in genetically susceptible children.
    Methods: Data was used from 6726 participants at genetic risk of type 1 diabetes and celiac disease enrolled in the observational cohort, The Environmental Determinants of Diabetes in the Young (TEDDY) study. Children were annually screened for tissue transglutaminase autoantibodies (tTGAs) from age 2 y. Principal component analysis extracted dietary patterns, based on intake of 27 food groups assessed by 3-d food records at age 9 to 24 mo. The primary outcome was CDA (i.e., persistently tTGA-positive in at least 2 consecutive samples), and the secondary outcome was celiac disease. During follow-up to mean age 11.0 (standard deviation 3.6) y, 1296 (19.3%) children developed CDA, and 529 (7.9%) were diagnosed with celiac disease. Associations of adherence to dietary patterns (per 5-unit increase) with the study outcomes were estimated by Cox regression models adjusted for risk factors including gluten intake.
    Results: At age 9 mo, a dietary pattern higher in the food groups vegetable fats and milk was associated with reduced risk of CDA (hazard ratio [HR]: 0.88; 95% confidence interval [CI]: 0.79, 0.98; P = 0.02). At 24 mo, a dietary pattern higher in the food groups wheat, vegetable fats, and juices, and lower in milk, meat, and oats at age 24 mo was associated with increased risk of CDA (HR: 1.18; 95% CI: 1.05, 1.33; P < 0.001) and celiac disease (HR: 1.24; 95% CI: 1.03, 1.50; P = 0.03).
    Conclusions: Dietary patterns in early childhood are associated with risk of CDA and celiac disease in genetically predisposed children, independent of gluten intake.
    MeSH term(s) Child ; Humans ; Child, Preschool ; Adolescent ; Young Adult ; Adult ; Infant ; Celiac Disease/etiology ; Autoimmunity ; Transglutaminases/genetics ; Autoantibodies/genetics ; Genetic Predisposition to Disease ; Glutens/adverse effects
    Chemical Substances Transglutaminases (EC 2.3.2.13) ; Autoantibodies ; Glutens (8002-80-0)
    Language English
    Publishing date 2023-10-16
    Publishing country United States
    Document type Journal Article
    ZDB-ID 280048-2
    ISSN 1938-3207 ; 0002-9165
    ISSN (online) 1938-3207
    ISSN 0002-9165
    DOI 10.1016/j.ajcnut.2023.08.009
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Cytotoxicity-Related Gene Expression and Chromatin Accessibility Define a Subset of CD4+ T Cells That Mark Progression to Type 1 Diabetes.

    Bediaga, Naiara G / Garnham, Alexandra L / Naselli, Gaetano / Bandala-Sanchez, Esther / Stone, Natalie L / Cobb, Joanna / Harbison, Jessica E / Wentworth, John M / Ziegler, Annette-G / Couper, Jennifer J / Smyth, Gordon K / Harrison, Leonard C

    Diabetes

    2022  Volume 71, Issue 3, Page(s) 566–577

    Abstract: Type 1 diabetes in children is heralded by a preclinical phase defined by circulating autoantibodies to pancreatic islet antigens. How islet autoimmunity is initiated and then progresses to clinical diabetes remains poorly understood. Only one study has ... ...

    Abstract Type 1 diabetes in children is heralded by a preclinical phase defined by circulating autoantibodies to pancreatic islet antigens. How islet autoimmunity is initiated and then progresses to clinical diabetes remains poorly understood. Only one study has reported gene expression in specific immune cells of children at risk associated with progression to islet autoimmunity. We analyzed gene expression with RNA sequencing in CD4+ and CD8+ T cells, natural killer (NK) cells, and B cells, and chromatin accessibility by assay for transposase-accessible chromatin sequencing (ATAC-seq) in CD4+ T cells, in five genetically at risk children with islet autoantibodies who progressed to diabetes over a median of 3 years ("progressors") compared with five children matched for sex, age, and HLA-DR who had not progressed ("nonprogressors"). In progressors, differentially expressed genes (DEGs) were largely confined to CD4+ T cells and enriched for cytotoxicity-related genes/pathways. Several top-ranked DEGs were validated in a semi-independent cohort of 13 progressors and 11 nonprogressors. Flow cytometry confirmed that progression was associated with expansion of CD4+ cells with a cytotoxic phenotype. By ATAC-seq, progression was associated with reconfiguration of regulatory chromatin regions in CD4+ cells, some linked to differentially expressed cytotoxicity-related genes. Our findings suggest that cytotoxic CD4+ T cells play a role in promoting progression to type 1 diabetes.
    MeSH term(s) Adolescent ; Autoimmunity/genetics ; B-Lymphocytes/metabolism ; CD4-Positive T-Lymphocytes/immunology ; CD4-Positive T-Lymphocytes/metabolism ; CD4-Positive T-Lymphocytes/ultrastructure ; CD8-Positive T-Lymphocytes/metabolism ; Child ; Child, Preschool ; Chromatin/chemistry ; Cytotoxicity, Immunologic/genetics ; Diabetes Mellitus, Type 1/genetics ; Diabetes Mellitus, Type 1/immunology ; Disease Progression ; Gene Expression Regulation ; Genetic Predisposition to Disease ; Humans ; Islets of Langerhans/immunology ; Killer Cells, Natural/metabolism ; Sequence Analysis, RNA
    Chemical Substances Chromatin
    Language English
    Publishing date 2022-03-17
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 80085-5
    ISSN 1939-327X ; 0012-1797
    ISSN (online) 1939-327X
    ISSN 0012-1797
    DOI 10.2337/db21-0612
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: ISPAD Clinical Practice Consensus Guidelines 2014. Phases of type 1 diabetes in children and adolescents.

    Couper, Jennifer J / Haller, Michael J / Ziegler, Annette-G / Knip, Mikael / Ludvigsson, Johnny / Craig, Maria E

    Pediatric diabetes

    2014  Volume 15 Suppl 20, Page(s) 18–25

    MeSH term(s) Adolescent ; Adolescent Medicine/trends ; Autoimmunity ; Child ; Child, Preschool ; Diabetes Mellitus, Type 1/diagnosis ; Diabetes Mellitus, Type 1/genetics ; Diabetes Mellitus, Type 1/immunology ; Diabetes Mellitus, Type 1/physiopathology ; Diabetes Mellitus, Type 2/diagnosis ; Diabetes Mellitus, Type 2/genetics ; Diabetes Mellitus, Type 2/immunology ; Diabetes Mellitus, Type 2/physiopathology ; Diagnosis, Differential ; Disease Progression ; Evidence-Based Medicine ; Genetic Predisposition to Disease ; Humans ; Infant ; International Agencies ; Pediatrics/trends ; Precision Medicine ; Prediabetic State/diagnosis ; Prediabetic State/genetics ; Prediabetic State/immunology ; Prediabetic State/physiopathology ; Societies, Scientific
    Language English
    Publishing date 2014-10-16
    Publishing country Denmark
    Document type Journal Article ; Practice Guideline
    ZDB-ID 1502504-4
    ISSN 1399-5448 ; 1745-1426 ; 1399-543X
    ISSN (online) 1399-5448
    ISSN 1745-1426 ; 1399-543X
    DOI 10.1111/pedi.12188
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Children's erythrocyte fatty acids are associated with the risk of islet autoimmunity.

    Niinistö, Sari / Erlund, Iris / Lee, Hye-Seung / Uusitalo, Ulla / Salminen, Irma / Aronsson, Carin Andrén / Parikh, Hemang M / Liu, Xiang / Hummel, Sandra / Toppari, Jorma / She, Jin-Xiong / Lernmark, Åke / Ziegler, Annette G / Rewers, Marian / Akolkar, Beena / Krischer, Jeffrey P / Galas, David / Das, Siba / Sakhanenko, Nikita /
    Rich, Stephen S / Hagopian, William / Norris, Jill M / Virtanen, Suvi M

    Scientific reports

    2021  Volume 11, Issue 1, Page(s) 3627

    Abstract: Our aim was to investigate the associations between erythrocyte fatty acids and the risk of islet autoimmunity in children. The Environmental Determinants of Diabetes in the Young Study (TEDDY) is a longitudinal cohort study of children at high genetic ... ...

    Abstract Our aim was to investigate the associations between erythrocyte fatty acids and the risk of islet autoimmunity in children. The Environmental Determinants of Diabetes in the Young Study (TEDDY) is a longitudinal cohort study of children at high genetic risk for type 1 diabetes (n = 8676) born between 2004 and 2010 in the U.S., Finland, Sweden, and Germany. A nested case-control design comprised 398 cases with islet autoimmunity and 1178 sero-negative controls matched for clinical site, family history, and gender. Fatty acids composition was measured in erythrocytes collected at the age of 3, 6, and 12 months and then annually up to 6 years of age. Conditional logistic regression models were adjusted for HLA risk genotype, ancestry, and weight z-score. Higher eicosapentaenoic and docosapentaenoic acid (n - 3 polyunsaturated fatty acids) levels during infancy and conjugated linoleic acid after infancy were associated with a lower risk of islet autoimmunity. Furthermore, higher levels of some even-chain saturated (SFA) and monounsaturated fatty acids (MUFA) were associated with increased risk. Fatty acid status in early life may signal the risk for islet autoimmunity, especially n - 3 fatty acids may be protective, while increased levels of some SFAs and MUFAs may precede islet autoimmunity.
    MeSH term(s) Autoimmunity ; Breast Feeding ; Case-Control Studies ; Child ; Child, Preschool ; Erythrocytes/metabolism ; Fatty Acids/metabolism ; Female ; Humans ; Infant ; Islets of Langerhans/immunology ; Male ; Risk Factors
    Chemical Substances Fatty Acids
    Language English
    Publishing date 2021-02-11
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-021-82200-9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Pharmacokinetics and antibody responses to the CD3 antibody otelixizumab used in the treatment of type 1 diabetes.

    Hale, Geoff / Rebello, Peppy / Al Bakir, Ibrahim / Bolam, Emma / Wiczling, Pawel / Jusko, William J / Vandemeulebroucke, Evy / Keymeulen, Bart / Mathieu, Chantal / Ziegler, Annette-G / Chatenoud, Lucienne / Waldmann, Herman

    Journal of clinical pharmacology

    2010  Volume 50, Issue 11, Page(s) 1238–1248

    Abstract: Otelixizumab is a chimeric CD3 antibody that has been genetically engineered to remove the glycosylation site in the Fc domain. This limits its ability to bind to complement or Fc receptors and reduces the risk of adverse clinical reactions due to ... ...

    Abstract Otelixizumab is a chimeric CD3 antibody that has been genetically engineered to remove the glycosylation site in the Fc domain. This limits its ability to bind to complement or Fc receptors and reduces the risk of adverse clinical reactions due to cytokine release. In a trial for treatment of type 1 diabetes, a short treatment with otelixizumab resulted in a reduced requirement for insulin lasting at least 18 months. In the course of this trial, the blood concentrations of the antibody were measured by flow cytometry to determine its pharmacokinetic profile. Dose-dependent accumulation of otelixizumab was demonstrated and modeling of the data indicated that the terminal half-life was approximately 1.5 days. Antibody responses to otelixizumab were measured by 2 methods: a bridging enzyme-linked immunosorbent assay and surface plasmon resonance. The surface plasmon resonance method had a greater sensitivity and was able to detect responses in all patients, starting at 8 days after the commencement of therapy. Neutralizing antibodies were detected in a significant proportion of patients by days 22 to 29. Although no adverse clinical effects were associated with these antibody responses and they did not appear to affect the clearance of the drug, they might have important implications for possible retreatment of the patients.
    MeSH term(s) Antibodies, Monoclonal/administration & dosage ; Antibodies, Monoclonal/immunology ; Antibodies, Monoclonal/pharmacokinetics ; Antibodies, Monoclonal, Humanized ; CD3 Complex/immunology ; Diabetes Mellitus, Type 1/drug therapy ; Dose-Response Relationship, Drug ; Double-Blind Method ; Enzyme-Linked Immunosorbent Assay ; Flow Cytometry ; Half-Life ; Humans ; Hypoglycemic Agents/administration & dosage ; Hypoglycemic Agents/immunology ; Hypoglycemic Agents/pharmacokinetics ; Insulin/administration & dosage ; Surface Plasmon Resonance
    Chemical Substances Antibodies, Monoclonal ; Antibodies, Monoclonal, Humanized ; CD3 Complex ; Hypoglycemic Agents ; Insulin ; otelixizumab (I5HF2X04PB)
    Language English
    Publishing date 2010-02-10
    Publishing country England
    Document type Clinical Trial, Phase II ; Journal Article ; Multicenter Study ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
    ZDB-ID 188980-1
    ISSN 1552-4604 ; 0091-2700 ; 0021-9754
    ISSN (online) 1552-4604
    ISSN 0091-2700 ; 0021-9754
    DOI 10.1177/0091270009356299
    Database MEDical Literature Analysis and Retrieval System OnLINE

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