scholarly journals Insulitis in the pancreas of non-diabetic organ donors under age 25 years with multiple circulating autoantibodies against islet cell antigens

2021 ◽  
Author(s):  
Silke Smeets ◽  
Diedert Luc De Paep ◽  
Geert Stangé ◽  
Katrijn Verhaeghen ◽  
Bart Van der Auwera ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
High Risk ◽  
Islet Cell ◽  
Age Groups ◽  
Pancreatic Tissue ◽  
Organ Donors ◽  
Tissue Samples ◽  
Increased Risk ◽  
Islet Cell Antigens

AbstractAutoantibodies against islet cell antigens are routinely used to identify subjects at increased risk of symptomatic type 1 diabetes, but their relation to the intra-islet pathogenetic process that leads to positivity for these markers is poorly understood. We screened 556 non-diabetic organ donors (3 months to 24 years) for five different autoantibodies and found positivity in 27 subjects, 25 single- and two double autoantibody-positive donors. Histopathological screening of pancreatic tissue samples showed lesion characteristic for recent-onset type 1 diabetes in the two organ donors with a high-risk profile, due to their positivity for multiple autoantibodies and HLA-inferred risk. Inflammatory infiltrates (insulitis) were found in a small fraction of islets (<5%) and consisted predominantly of CD3+CD8+ T-cells. Islets with insulitis were found in close proximity to islets devoid of insulin-positivity; such pseudo-atrophic islets were present in multiple small foci scattered throughout the pancreatic tissue or were found to be distributed with a lobular pattern. Relative beta cell area in both single and multiple autoantibody-positive donors was comparable to that in autoantibody-negative controls. In conclusion, in organ donors under age 25 years, insulitis and pseudo-atrophic islets were restricted to multiple autoantibody-positive individuals allegedly at high risk of developing symptomatic type 1 diabetes, in line with reports in older age groups. These observations may give further insight into the early pathogenetic events that may culminate in clinically overt disease.

Relation between Cellular and Humoral Immunity to Islet Cell Antigens in Type 1 Diabetes

1996 ◽  
Vol 9 (3) ◽  
pp. 427-430 ◽  
Author(s):  
Michael Hummel ◽  
Ivana Durinovic-Bello ◽  
Anette-G. Ziegler
Keyword(s):  
Type 1 Diabetes ◽  
Humoral Immunity ◽  
Islet Cell ◽  
Cellular And Humoral Immunity ◽  
Islet Cell Antigens

scholarly journals Occurrence of Type 1 Diabetes in Graves' Disease Patients Who Are Positive for Antiglutamic Acid Decarboxylase Antibodies: An 8-Year Followup Study

2011 ◽  
Vol 2011 ◽  
pp. 1-4
Author(s):  
Matsuo Taniyama ◽  
Akira Kasuga ◽  
Chieko Nagayama ◽  
Koichi Ito
Keyword(s):  
Type 1 Diabetes ◽  
High Risk ◽  
Glutamic Acid Decarboxylase ◽  
Islet Cell ◽  
Antithyroid Drug ◽  
Acid Decarboxylase ◽  
Graves Disease ◽  
Drug Resistant ◽  
Glutamic Acid Decarboxylase Antibodies

Glutamic acid decarboxylase antibodies (GADAs) are one of the markers of islet cell autoimmunity and are sometimes present before the onset of type 1 diabetes (T1D). GADA can be present in Graves' patients without diabetes; however, the outcome of GADA-positive Graves' patients is not fully understood, and the predictive value of GADA for the development of T1D in Graves' patients remains to be clarified. We investigated the prevalence of GADA in 158 patients with Graves' disease and detected GADA in 10 patients. They were followed up to discover whether or not T1D developed. In the course of eight years, 2 patients with high titers of GADA developed T1D, both had long-standing antithyroid drug-resistant Graves' disease. Thus, Graves' disease with high GADA titer seems to be at high risk for T1D.

scholarly journals One in Ten CD8+ Cells in the Pancreas of Living Individuals With Recent Onset Type 1 Diabetes Recognizes the Preproinsulin Epitope PPI15-24

2021 ◽  
Author(s):  
Ada Admin ◽  
Teresa Rodriguez-Calvo ◽  
Lars Krogvold ◽  
Natalie Amirian ◽  
Knut Dahl-Jørgensen ◽  
...  
Keyword(s):  
T Cells ◽  
Type 1 Diabetes ◽  
T Cell ◽  
Cd8 T Cells ◽  
Pancreatic Tissue ◽  
Cell Reactivity ◽  
Tissue Samples ◽  
Recent Onset ◽  
Onset Type

In type 1 diabetes, a lifelong autoimmune disease, T cells infiltrate the islets and the exocrine pancreas in high numbers. CD8+ T cells are the main cell type found in the insulitic lesion, and CD8+ T cells reactive against beta cell antigens have been detected in the periphery and in the pancreas of subjects with short and long disease duration. The Diabetes Virus Detection (DiViD) study collected pancreatic tissue, by pancreatic tail resection, from living patients with recent-onset type 1 diabetes. These tissues have been extensively studied by the scientific community, but the autoreactive nature of the T cell infiltrate has remained unexplored. Our objective was to determine the number and localization of these cells in pancreas samples obtained through the DiViD study. Here, we demonstrate the presence of high frequencies of CD8+ T cells reactive against a highly relevant epitope derived from the preproinsulin signal peptide in pancreatic tissue samples from these donors. We additionally show the heterogeneity of islet distribution and CD8+ T cell infiltration. Our findings contribute to the current limited existing knowledge on T cell reactivity in the pancreas of recent onset type 1 diabetic donors, and indicate that antigen-specific therapies directed towards preproinsulin could have high clinical impact.

scholarly journals Characterization of plasma lipidomics in adolescent subjects with increased risk for type 1 diabetes in the DiPiS cohort

Metabolomics ◽  
2020 ◽  
Vol 16 (10) ◽  
Author(s):  
Agnes Andersson Svärd ◽  
◽  
Simranjeet Kaur ◽  
Kajetan Trôst ◽  
Tommi Suvitaival ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
High Risk ◽  
High Performance ◽  
Plasma Lipids ◽  
High Risk Population ◽  
Cross Sectional ◽  
Flight Mass Spectrometry ◽  
Insulin Autoantibody ◽  
Increased Risk

Abstract Introduction Type 1 diabetes (T1D) is caused by the destruction of pancreatic islet beta cells resulting in total loss of insulin production. Recent studies have suggested that the destruction may be interrelated to plasma lipids. Objectives Specific lipids have previously been shown to be decreased in children who develop T1D before four years of age. Disturbances of plasma lipids prior to clinical diagnosis of diabetes, if true, may provide a novel way to improve prediction, and monitor disease progression. Methods A lipidomic approach was utilized to analyze plasma from 67 healthy adolescent subjects (10–15 years of age) with or without islet autoantibodies but all with increased genetic risk for T1D. The study subjects were enrolled at birth in the Diabetes Prediction in Skåne (DiPiS) study and after 10–15 years of follow-up we performed the present cross-sectional analysis. HLA-DRB345, -DRB1, -DQA1, -DQB1, -DPA1 and -DPB1 genotypes were determined using next generation sequencing. Lipidomic profiles were determined using ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometry. Lipidomics data were analyzed according to genotype. Results Variation in levels of several specific phospholipid species were related to level of autoimmunity but not development of T1D. Five glycosylated ceramides were increased in insulin autoantibody (IAA) positive adolescent subjects compared to adolescent subjects without this autoantibody. Additionally, HLA genotypes seemed to influence levels of long chain triacylglycerol (TG). Conclusion Lipidomic profiling of adolescent subjects in high risk of T1D may improve sub-phenotyping in this high risk population.

scholarly journals Detection of enterovirus protein and RNA in multiple tissues from nPOD organ donors with type 1 diabetes

2018 ◽  
Author(s):  
Maarit Oikarinen ◽  
Jutta E Laiho ◽  
Sami Oikarinen ◽  
Sarah J Richardson ◽  
Irina Kusmartseva ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Lymph Nodes ◽  
Pancreatic Islets ◽  
Lymphoid Tissues ◽  
Small Intestinal Mucosa ◽  
Organ Donors ◽  
Tissue Samples ◽  
Multiple Organs ◽  
Pancreatic Lymph Nodes

AbstractEpidemiological studies have shown an association between enterovirus (EV) infections and type 1 diabetes (T1D), and EV protein has been detected in the pancreatic islets of T1D patients. Here we correlated the detection of EVs in lymphoid tissues (spleen and pancreatic lymph nodes) and small intestinal mucosa to the virus detection in the pancreas of T1D, autoantibody-positive (aab+) and non-diabetic control organ donors of the Network for Pancreatic Organ Donors with Diabetes (nPOD) study. Formalin-fixed paraffin-embedded tissue samples were screened for insulin and EV protein using immunohistochemistry, and frozen tissue for EV genome using RT-PCR. The presence of EV protein in the pancreatic islets correlated with the presence of insulin-positive cells. Altogether 62 % of T1D and aab+ donors were positive for EV protein in pancreatic islets (only insulin-positive donors included), 40 % in duodenum and 32 % in spleen, compared to 33 %, 14 %, and 27 % of non-diabetic controls. Pancreatic lymph nodes were positive for EV protein in 60 % of T1D and aab+ cases. T1D and aab+ donors were more frequently VP1-positive in multiple organs than control donors (39 % vs. 11 %; including only insulin-positive donors). EV RNA was found in selected donors and from multiple tissue types except for duodenum, and individual T1D and aab+ donors were EV RNA-positive in multiple organs. The role of extra-pancreatic organs and their interplay with EV in T1D pathogenesis remains to be solved, but we hypothesize that these organs may serve as a reservoir for the virus which may reside in these tissues in a slow-replicating persistent form.

scholarly journals One in Ten CD8+ Cells in the Pancreas of Living Individuals With Recent Onset Type 1 Diabetes Recognizes the Preproinsulin Epitope PPI15-24

2021 ◽  
Author(s):  
Ada Admin ◽  
Teresa Rodriguez-Calvo ◽  
Lars Krogvold ◽  
Natalie Amirian ◽  
Knut Dahl-Jørgensen ◽  
...  
Keyword(s):  
T Cells ◽  
Type 1 Diabetes ◽  
T Cell ◽  
Cd8 T Cells ◽  
Pancreatic Tissue ◽  
Cell Reactivity ◽  
Tissue Samples ◽  
Recent Onset ◽  
Onset Type

In type 1 diabetes, a lifelong autoimmune disease, T cells infiltrate the islets and the exocrine pancreas in high numbers. CD8+ T cells are the main cell type found in the insulitic lesion, and CD8+ T cells reactive against beta cell antigens have been detected in the periphery and in the pancreas of subjects with short and long disease duration. The Diabetes Virus Detection (DiViD) study collected pancreatic tissue, by pancreatic tail resection, from living patients with recent-onset type 1 diabetes. These tissues have been extensively studied by the scientific community, but the autoreactive nature of the T cell infiltrate has remained unexplored. Our objective was to determine the number and localization of these cells in pancreas samples obtained through the DiViD study. Here, we demonstrate the presence of high frequencies of CD8+ T cells reactive against a highly relevant epitope derived from the preproinsulin signal peptide in pancreatic tissue samples from these donors. We additionally show the heterogeneity of islet distribution and CD8+ T cell infiltration. Our findings contribute to the current limited existing knowledge on T cell reactivity in the pancreas of recent onset type 1 diabetic donors, and indicate that antigen-specific therapies directed towards preproinsulin could have high clinical impact.

Rotavirus Infection Enhances Levels of Autoantibodies Against Islet Cell Antigens GAD65 and IA-2 in Children with Type 1 Diabetes

2018 ◽  
Vol 38 (2) ◽  
pp. 103-111 ◽  
Author(s):  
Angila Ataei-Pirkooh ◽  
Mona Tehrani ◽  
Hossein Keyvani ◽  
Maryam Esghaei ◽  
Ahmad Tavakoli ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Islet Cell ◽  
Rotavirus Infection ◽  
Islet Cell Antigens

Autoimmune diagnostics in diabetes mellitus

2006 ◽  
Vol 44 (2) ◽  
Author(s):  
Jochen Seissler ◽  
Werner A. Scherbaum
Keyword(s):  
Type 1 Diabetes ◽  
Islet Cell ◽  
Autoimmune Diabetes ◽  
Tyrosine Phosphatase ◽  
Islet Cell Antibodies ◽  
Acid Decarboxylase ◽  
Latent Autoimmune Diabetes ◽  
Islet Cell Antigens

AbstractType 1 diabetes results from a specific destruction of the insulin-producing β-cells of the pancreas. The disease is characterized by the appearance of specific autoantibodies against islet cell antigens. Autoantibodies to insulin, glutamic acid decarboxylase, tyrosine phosphatase IA-2 and cytoplasmic islet cell antibodies are useful markers for the differential diagnosis of type 1 diabetes when clinical and metabolic criteria alone do not allow definite classification. Autoimmune diagnostics is of particular importance in adults to discriminate between type 1 and type 2 diabetes and to assess the diagnosis of latent autoimmune diabetes in adults.

Organ-specific autoimmunity in relation to clinical characteristics in children with long-lasting type 1 diabetes

2016 ◽  
Vol 29 (6) ◽  
Author(s):  
Barbara Głowińska-Olszewska ◽  
Justyna Michalak ◽  
Włodzimierz Łuczyński ◽  
Maria del Pilar Larosa ◽  
Shu Chen ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Islet Cell ◽  
Tissue Transglutaminase ◽  
Acid Decarboxylase ◽  
Thyroid Peroxidase ◽  
Autoimmune Thyroid ◽  
Organ Specific ◽  
Autoimmune Conditions ◽  
Islet Cell Antigens

AbstractThe aim of this study was to assess the prevalence of diabetes and other organ-specific autoantibodies (Ab) associated with various autoimmune conditions, in Polish children with type 1 diabetes mellitus (T1DM).In this study 114 patients, aged 13.4 years, with mean diabetes duration 5.2 years were included. Ab to islet cell antigens: glutamic acid decarboxylase (GAD), insulinoma antigen 2 (IA-2), zinc transporter 8 (ZnT8), together with thyroid peroxidase Ab (TPO Ab), thyroglobulin Ab (Tg Ab), tissue transglutaminase Ab (tTG Ab) and 21-hydroxylase Ab (21-OH Ab) were measured.The prevalence of at least one diabetes associated Ab was found in 87%, with the highest prevalence of 64% for ZnT8 Ab. In patients with disease duration <5 years, at least one antibody was present in 90%, the most prevalent was ZnT8 Ab (72%). In patients with duration >10 years, 50% had at least one antibody. The prevalence of other than islet cell autoimmunity was high (34%). Thyroid Ab were detected in 26% patients, 42% in girls vs. 8% in boys, p<0.001. tTG Ab were found in 11% patients, with a greater prevalence in children with early onset (p=0.01). 21-OH Ab were found in 2.6% T1DM patients.Islet Ab were found in most T1DM children and remained positive even 10 years after onset. ZnT8 Ab emerged as an important marker for the diagnosis of T1DM in the Polish children. Screening for non-diabetes Ab in T1DM may be helpful in identifying subclinical cases of autoimmune thyroid, celiac or Addison’s disease (AD).

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