Article
Endocrinology & Metabolism
Bum Chul Kwon, Peter Achenbach, Vibha Anand, Brigitte I. Frohnert, William Hagopian, Jianying Hu, Eileen Koski, Ake Lernmark, Olivia Lou, Frank Martin, Kenney Ng, Jorma Toppari, Riitta Veijola
Summary: Analyzing the levels of autoantibodies can better differentiate children who progress to type 1 diabetes from those who do not.
Article
Immunology
Sulafa Elhassan, Fran Dong, Teresa Buckner, Randi K. Johnson, Jennifer A. Seifert, Patrick M. Carry, Lauren Vanderlinden, Kathleen Waugh, Marian Rewers, Jill M. Norris
Summary: Studies have shown that iron intake may be associated with the risk of developing type 1 diabetes. This study found that individuals with high iron intake had a lower risk of developing type 1 diabetes compared to those with moderate iron intake.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Endocrinology & Metabolism
Kenney Ng, Harry Stavropoulos, Vibha Anand, Riitta Veijola, Jorma Toppari, Marlena Maziarz, Markus Lundgren, Kathy Waugh, Brigitte Frohnert, Frank Martin, William Hagopian, Peter Achenbach
Summary: This study defined islet autoantibody type-specific titer thresholds that significantly improved type 1 diabetes risk stratification in children.
Review
Endocrinology & Metabolism
Peter J. Thompson, Jasmine Pipella, Guy A. Rutter, Herbert Y. Gaisano, Pere Santamaria
Summary: Type 1 diabetes occurs when the body's immune system mistakenly attacks and destroys pancreatic beta cells. This review highlights recent advances in understanding how early life exposures and stress response pathways impact beta cells and contribute to the autoimmune process in type 1 diabetes. Progress in this area holds promise for developing targeted therapies that could be implemented in the early stages of the disease, potentially in combination with immunotherapies.
Article
Public, Environmental & Occupational Health
Essi J. Peltonen, Riitta Veijola, Jorma Ilonen, Mikael Knip, Harri Niinikoski, Jorma Toppari, Helena E. Virtanen, Suvi M. Virtanen, Jaakko Peltonen, Jaakko Nevalainen
Summary: In many populations, the peak incidence of type 1 diabetes (T1D) occurs during puberty, but the direct evidence of the role of puberty in T1D development is limited. This study aimed to investigate the association between puberty and the development of islet autoimmunity (IA) and subsequent progression to T1D. The results showed that puberty is associated with an increased risk of progression to T1D, but not a risk factor for IA.
EUROPEAN JOURNAL OF EPIDEMIOLOGY
(2023)
Review
Endocrinology & Metabolism
Michelle So, Cate Speake, Andrea K. Steck, Markus Lundgren, Peter G. Colman, Jerry P. Palmer, Kevan C. Herold, Carla J. Greenbaum
Summary: Islet autoantibodies are key markers for diagnosing type 1 diabetes and identifying at-risk individuals pre-symptomatically. Prediction of disease progression based on autoantibody count has been shown to be effective, but heterogeneous. Characteristics such as molecular specifics and sequence-dependent risk profiles have emerged as predictive features. Studying these features can improve trial design aimed at predicting and preventing disease.
Article
Immunology
Julie Vandewalle, Aster K. Desouter, Bart J. van der Auwera, Sylvie Tenoutasse, Pieter Gillard, Christophe De Block, Bart Keymeulen, Frans K. Gorus, Mark van de Casteele, Belgian Diabetes Registry
Summary: The HLA region is the major genetic risk determinant of Type 1 diabetes. Non-HLA loci, such as INS, SH2B3, PTPN2, PTPN22, CTLA4, CLEC16A, and IL2RA, may also contribute to the genetic risk by impacting the progression of asymptomatic autoimmunity. In this study, the researchers investigated the relationship between SNPs in these susceptibility loci and the progression from single to multiple autoantibody positivity, as well as the development of clinical diabetes. They found that certain genotypes in CTLA4 and CLEC16A were associated with accelerated progression from single to multiple autoantibody positivity, but their effects were limited to specific conditions. The interaction between CTLA4 and HLA-DQ2/DQ8 was found to override the effect of HLA-DQ2/DQ8 alone. The study also showed that SH2B3 genotype was protective for HLA-DQ8 positive subjects, while CTLA4 genotype was a minor independent risk factor for progression towards clinical diabetes. The findings suggest that non-HLA polymorphisms impact the progression of islet autoimmunity in specific ways and may have implications for risk assessment and prevention trials in at-risk groups.
CLINICAL AND EXPERIMENTAL IMMUNOLOGY
(2023)
Review
Medicine, General & Internal
Ake Lernmark, Beena Akolkar, William Hagopian, Jeffrey Krischer, Richard McIndoe, Marian Rewers, Jorma Toppari, Kendra Vehik, Anette-G. Ziegler, TEDDY Study Grp
Summary: The etiology of type 1 diabetes involves pancreatic islet beta-cell autoimmune pathogenesis that leads to the clinical onset of the disease. By testing autoantibodies against insulin, glutamic acid decarboxylase, islet antigen-2, and ZnT8 transporter, children can be monitored from birth until the appearance of the first islet autoantibody. The incidence rate of the first-appearing autoantibody follows two different patterns, and an innate immune reaction may precede the adaptive response.
JOURNAL OF INTERNAL MEDICINE
(2023)
Article
Endocrinology & Metabolism
Qian Li, Xiang Liu, Jimin Yang, Iris Erlund, Ake Lernmark, William Hagopian, Marian Rewers, Jin-Xiong She, Jorma Toppari, Anette-G. Ziegler, Beena Akolkar, Jeffrey P. Krischer
Summary: The study found that children's plasma lipidome can reflect gene regulation and dietary exposure, predicting the development of islet autoantibodies and type 1 diabetes. Infants with reduced plasma ascorbic acid and cholesterol experienced IAA-first earlier, while those with early onset of GADA-first had reduced sphingomyelins in infancy. Plasma ascorbic acid and 25(OH)D were lower in HLA-DR3/DR4 children among IA case subjects, suggesting dysregulation of circulating vitamins as potential signals for IA or T1D progression.
Review
Medicine, General & Internal
Anna-Maria Lampousi, Sofia Carlsson, Josefin E. Lofvenborg
Summary: Breastfeeding and late introduction of gluten, fruit, and cow's milk may reduce the risk of T1D, while high childhood intake of cow's milk may increase it.
Review
Biochemistry & Molecular Biology
Witold Bauer, Attila Gyenesei, Adam Kretowski
Summary: Type 1 Diabetes (T1D) is caused by autoimmune destruction of insulin producing pancreatic ss-cells, leading to the lifelong need for insulin injections and careful monitoring of blood glucose levels. Despite current therapies, T1D still shortens life expectancy due to complications affecting multiple organs. The incidence of T1D in childhood is increasing, and the disease process is influenced by genetic susceptibility, environmental factors, and the number of autoimmune antibodies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Endocrinology & Metabolism
Ekua W. Brenu, Mark Harris, Emma E. Hamilton-Williams
Summary: This systematic review evaluates novel circulating biomarkers associated with future progression to type 1 diabetes (T1D). The study found that some circulating biomarkers are dysregulated before T1D diagnosis and may be useful in predicting the risk and rate of progression to T1D. However, further research is needed to validate these biomarkers and assess their predictive accuracy.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Endocrinology & Metabolism
Randi K. Johnson, Roy Tamura, Nicole Frank, Ulla Uusitalo, Jimin Yang, Sari Niinisto, Carin Andren Aronsson, Anette-G. Ziegler, William Hagopian, Marian Rewers, Jorma Toppari, Beena Akolkar, Jeffrey Krischer, Suvi M. Virtanen, Jill M. Norris
Summary: The study found that maternal food consumption during late pregnancy was not significantly associated with offspring risk for IA or type 1 diabetes.
Review
Nutrition & Dietetics
Valdemar Brimnes Ingemann Johansen, Knud Josefsen, Julie Christine Antvorskov
Summary: This study systematically reviewed the association between maternal dietary factors during gestation and the risk of developing type 1 diabetes and/or islet autoimmunity (IA) in offspring. The most investigated dietary factors were gluten, dietary advanced glycosylated end products (dAGEs), vitamin D, fatty acids, and iron. The results showed that prenatal exposure to a gluten-free environment and certain fatty acids and vitamin D had protective effects against IA development, while in utero exposure to iron and fat correlated with increased risks of IA.
Article
Immunology
Anna-Mari Schroderus, Josh Poorbaugh, Samantha McElyea, Stephanie Beasley, Lin Zhang, Kirsti Nanto-Salonen, Reeta Rintamaki, Jussi Pihlajamaki, Mikael Knip, Riitta Veijola, Jorma Toppari, Jorma Ilonen, Robert J. Benschop, Tuure Kinnunen
Summary: This study aimed to examine plasma IL-21 levels in individuals at different stages of type 1 diabetes progression. The results showed that adults with established type 1 diabetes had higher plasma IL-21 levels compared to healthy controls, but no significant correlation was found with clinical variables. In children, plasma IL-21 levels were almost ten times higher, but no significant differences were detected between different groups.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Pediatrics
Owen Martyn Bendor-Samuel, Tabitha Wishlade, Louise Willis, Parvinder Aley, Edward Choi, Rachel Craik, Yama Mujadidi, Ginny Mounce, Fenella Roseman, Arancha De la Horra Gozalo, James Bland, Nazia Taj, Ian Smith, Anette-Gabriele Ziegler, Ezio Bonifacio, Christiane Winkler, Florian Haupt, John A. Todd, Laurent Servais, Matthew D. Snape, Manu Vatish
Summary: This study investigates the use of prospective consent in a research study on genetic risk for Type 1 Diabetes using newborn screening blood spots. The methodology serves as a model for future population-based genetic research.
ARCHIVES OF DISEASE IN CHILDHOOD
(2023)
Article
Cell Biology
Yannick F. Fuchs, Jonathan Brunner, Marc Weigelt, Anja Schieferdecker, Robert Morgenstern, Andrea Sturm, Boris Winter, Helena Jambor, Friedrich Stolzel, Leo Ruhnke, Malte von Bonin, Elke Rucker-Braun, Falk Heidenreich, Anke Fuchs, Ezio Bonifacio, Martin Bornhauser, David M. Poitz, Heidi Altmann
BIOPRESERVATION AND BIOBANKING
(2023)
Article
Medicine, General & Internal
Raffael Ott, Peter Achenbach, Dominik A. Ewald, Nadine Friedl, Gita Gemulla, Michael Hubmann, Olga Kordonouri, Anja Loff, Erika Marquardt, Philipp Sifft, Melanie Sporreiter, Jose Zapardiel-Gonzalo, Anette-G. Ziegler
Summary: A study conducted in Bavaria, Germany revealed a significant increase in SARS-CoV-2 infections among children and adolescents from late 2021 to mid-2022. School-age children had a higher infection rate compared to preschool children. The high infection rate among children with low vaccination coverage should be considered when developing health policies.
DEUTSCHES ARZTEBLATT INTERNATIONAL
(2022)
Article
Endocrinology & Metabolism
Kenney Ng, Vibha Anand, Harry Stavropoulos, Riitta Veijola, Jorma Toppari, Marlena Maziarz, Markus Lundgren, Kathy Waugh, Brigitte Frohnert, Frank Martin, Olivia Lou, William Hagopian, Peter Achenbach
Summary: This study aimed to investigate the usefulness of islet autoantibody (IAb) levels in predicting type 1 diabetes in children positive for autoantibodies. The results showed that considering the quantitative patterns of IAb levels improved the predictive power for type 1 diabetes beyond the qualitative IAb positivity status in children positive for autoantibodies.
Review
Biophysics
Manisha Goel, Anne Eugster, Johannes Schetelig, Ezio Bonifacio, Martin Bornhaeuser, Cornelia S. Link-Rachner
Summary: Graft-versus-host disease (GvHD) is a common complication following allogeneic haematopoietic stem cell transplantation (allo-HSCT), in which T cells play a key role. Monitoring the changes in the T cell receptor (TCR) repertoire can provide insights into the dynamics of the T cell population and the underlying mechanisms of GvHD.
BONE MARROW TRANSPLANTATION
(2023)
Article
Endocrinology & Metabolism
Sarah C. Shuck, Peter Achenbach, Bart O. Roep, John S. Termini, Carlos Hernandez-Castillo, Christiane Winkler, Andreas Weiss, Anette-Gabriele Ziegler
Summary: The study found that serum levels of MG-AGEs were associated with the rate of progression to stage 3 type 1 diabetes, with lower levels increasing the risk of progression. This provides a potential new clinical biomarker for determining the rate of disease progression and points to contributing metabolic pathways.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Pediatrics
Mohamed Ghalwash, Vibha Anand, Olivia Lou, Frank Martin, Marian Rewers, Anette-G Ziegler, Jorma Toppari, William A. Hagopian, Riitta Veijola
Summary: Screening for islet autoantibodies in adolescents aged 10-18 can effectively predict the development of type 1 diabetes, allowing for education and prevention measures.
LANCET CHILD & ADOLESCENT HEALTH
(2023)
Article
Medicine, General & Internal
Jean Van Rampelbergh, Peter Achenbach, Richard David Leslie, Mohammad Alhadj Ali, Colin Dayan, Bart Keymeulen, Katharine R. Owen, Martin Kindermans, Frederic Parmentier, Vincent Carlier, Roxana R. Ahangarani, Evelien Gebruers, Nicolas Bovy, Luc Vanderelst, Marcelle Van Mechelen, Pierre Vandepapeliere, Christian Boitard
Summary: IMCY-0098, a peptide derived from human proinsulin, shows promising safety profile and preliminary clinical response in patients with recent-onset T1D, suggesting its potential as a treatment option. Further studies are needed to validate its efficacy.
Article
Endocrinology & Metabolism
Brigitte I. Frohnert, Mohamed Ghalwash, Ying Li, Kenney Ng, Jessica L. Dunne, Markus Lundgren, William Hagopian, Olivia Lou, Christiane Winkler, Jorma Toppari, Riitta Veijola, Vibha Anand
Summary: The risk of progression to stage 3 type 1 diabetes varies significantly based on the definition of multiple islet autoantibody positivity. The 15-year cumulative incidence of diabetes ranges from 18% to 88%. Short-term follow-up can help stratify evolving risk, especially for those with less stringent definitions of multiple islet autoantibody positivity.
Article
Endocrinology & Metabolism
Ilaria Marzinotto, David L. L. Pittman, Alistair J. K. Williams, Anna E. E. Long, Peter Achenbach, Michael Schlosser, Beena Akolkar, William E. E. Winter, Vito Lampasona
Summary: The Islet Autoantibody Standardization Program (IASP) aims to improve the performance and consistency of immunoassays measuring autoantibodies in type 1 diabetes. Results from IASP workshops in 2018 and 2020 showed variability in assay performance, with in-house radiobinding assay (RBA) still considered the gold standard. However, non-radioactive IAA immunoassays showed promising results and could be potential alternatives to RBAs.
Article
Endocrinology & Metabolism
Sandra Hummel, Johanna Carl, Nadine Friedl, Christiane Winkler, Kerstin Kick, Joanna Stock, Franziska Reinmueller, Claudia Ramminger, Jennifer Schmidt, Dominik Lwowsky, Sonja Braig, Desiree Dunstheimer, Uwe Ermer, Eva-Maria Gerstl, Leonie Weber, Nicole Nellen-Hellmuth, Susanne Braemswig, Marina Sindichakis, Stefanie Tretter, Anja Lorrmann, Ezio Bonifacio, Anette-G. Ziegler, Peter Achenbach
Summary: This study aimed to determine whether the severity of clinical onset of type 1 diabetes in children could be reduced by early detection and monitoring. Clinical data from children with presymptomatic type 1 diabetes who were diagnosed early and received education and monitoring were compared with data from children who were diagnosed with type 1 diabetes at a similar age without prior screening. The results showed that children with a prior early-stage diagnosis had better clinical outcomes at the onset of type 1 diabetes.
Article
Immunology
Sara Puente-Marin, Fabricia Dietrich, Peter Achenbach, Hugo Barcenilla, Johnny Ludvigsson, Rosaura Casas
Summary: GAD-alum injections into lymph nodes had a positive effect on T1D patients with DR3DQ2 haplotype, showing better preservation of C-peptide. Patients receiving GAD-alum had higher levels of GADA, GADA subclasses, GAD(65)-induced proliferation, and cytokine secretion compared to the placebo group. Good responders with DR3DQ2 haplotype had a distinct cellular immune response to GAD-alum injections, associated with increased IL13 secretion and proliferation.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Medicine, General & Internal
Tomi Suomi, Inna Starskaia, Ubaid Ullah Kalim, Omid Rasool, Maria K. Jaakkola, Toni Gronroos, Tommi Valikangas, Caroline Brorsson, Gianluca Mazzoni, Sylvaine Bruggraber, Lut Overbergh, David Dunger, Mark Peakman, Piotr Chmura, Seren Brunak, Anke M. Schulte, Chantal Mathieu, Mikael Knip, Riitta Lahesmaa, Laura L. Elo
Summary: This study aimed to identify transcriptional changes associated with disease progression in patients with recent-onset type 1 diabetes. They found that genes and pathways related to innate immunity were downregulated during the first year after diagnosis. Associations between gene expression changes and ZnT8A autoantibody positivity were also observed. Additionally, changes in the expression of 16 genes were found to predict the decline in C-peptide at 24 months, and increased B cell levels and decreased neutrophil levels were associated with rapid progression, consistent with previous reports.
Letter
Endocrinology & Metabolism
Sandra Hummel, Nadine Friedl, Christiane Winkler, Anette-G. Ziegler, Peter Achenbach
Article
Medicine, General & Internal
Katharina Warncke, Alexander Eckert, Ezio Bonifacio, Peter Achenbach, Olga Kordonouri, Thomas Meissner, Ute Ohlenschlaeger, Walter Bonfig, Anette-G. Ziegler, Reinhard W. Holl
Summary: This study aimed to determine whether subgroups of childhood diabetes are associated with diabetes-specific complications and could be a basis for personalised therapies. The researchers found that subgrouping of childhood diabetes at diagnosis could provide prognostic value for the development of acute and chronic diabetes-specific complications.
Article
Immunology
Shane Kelly, Katherine J. L. Jackson, Timothy J. Peters, Dan Suan, Christopher C. Goodnow
Summary: This study successfully identified and characterized PR3-specific B cells from the peripheral blood of patients with PR3 autoantibodies. These cells exhibited specific immunological features, suggesting that PR3 self-reactivity may occur early in B-cell development.
JOURNAL OF AUTOIMMUNITY
(2024)
Article
Immunology
Ana Merino-Vico, Jan Piet van Hamburg, Paul Tuijnenburg, Giulia Frazzei, Aram Al-Soudi, Carlo G. Bonasia, Boy Helder, Abraham Rutgers, Wayel H. Abdulahad, Coen A. Stegeman, Jan-Stephan Sanders, Laura Bergamaschi, Paul A. Lyons, Theo Bijma, Laura van Keep, Kirsten Wesenhagen, Aldo Jongejan, Henric Olsson, Niek de Vries, Taco W. Kuijpers, Peter Heeringa, Sander W. Tas
Summary: B lineage cells play a critical role in ANCA-associated vasculitis (AAV), and the transcription factor NF-kappa B may be a potential therapeutic target for AAV and other autoimmune diseases with prominent B cell involvement.
JOURNAL OF AUTOIMMUNITY
(2024)
Article
Immunology
Christopher Nelke, Thomas Muentefering, Derya Cengiz, Lukas Theissen, Vera Dobelmann, Christina B. Schroeter, Helena Block, Corinna Preu, Alexander P. E. Michels, Stefanie Lichtenberg, Marc Pawlitzki, Steffen Pfeuffer, Niklas Huntemann, Alexander Zarbock, Thorben Briese, Christoph Kittl, Carsten Dittmayer, Thomas Budde, Ingrid E. Lundberg, Werner Stenzel, Sven G. Meuth, Tobias Ruck
Summary: K2P2.1 plays a regulatory role in the autoimmune response of idiopathic inflammatory myopathies (IIMs), by regulating inflammatory cell response, adhesion, and transmigration in both endothelial and skeletal muscle cells. Inhibiting K2P2.1 enhances the inflammatory response, while activating K2P2.1 improves the disease course.
JOURNAL OF AUTOIMMUNITY
(2024)
Article
Immunology
Xuan Zhang, Jun Xia, Ying Jiang, David S. Pisetsky, Josef S. Smolen, Rong Mu, Shengming Dai, Michael E. Weinblatt, Tore K. Kvien, Juan Li, Thomas Doerner, Yu Zhang, Liwei Lu, Chengde Yang, Pingting Yang, Yuan Zhang, Chenchen Xu, Zhan Zhao, Peter E. Lipsky
Summary: The study suggests that TwHF may be as effective as MTX in treating active RA, and combination therapy may be more effective than monotherapy.
JOURNAL OF AUTOIMMUNITY
(2024)
Article
Immunology
Maya F. Amjadi, Maxwell H. Parker, Ryan R. Adyniec, Zihao Zheng, Alex M. Robbins, S. Janna Bashar, Michael F. Denny, Sara S. Mccoy, Irene M. Ong, Miriam A. Shelef
Summary: Rheumatoid factors (RFs) are polyreactive antibodies that can bind disease-specific epitopes. Recent studies have found that RFs in COVID-19 can bind novel IgG epitopes, which provides new insights into the mechanism of RFs.
JOURNAL OF AUTOIMMUNITY
(2024)
Article
Immunology
Johanne Liberatore, Yann Nguyen, Jerome Hadjadj, Pascal Cohen, Luc Mouthon, Xavier Puechal, Loic Guillevin, Benjamin Terrier
Summary: B-cell depletion induced by rituximab (RTX) in ANCA-associated vasculitis (AAV) can lead to decreased gammaglobulin levels, which is associated with an increased risk of relapse and severe infections. Older age, low gammaglobulin levels, and receiving pulses of methylprednisolone at induction therapy are risk factors for gammaglobulin decline.
JOURNAL OF AUTOIMMUNITY
(2024)