Humoral and cellular immune responses to proinsulin in adults with newly diagnosed type 1 diabetes

Autor: Parth Narendran, Colin M. Dayan, Alistair J K Williams, Nicola J. Leech, KA Elsegood
Rok vydání: 2003
Předmět:
Adult
endocrine system
medicine.medical_specialty
Cellular immunity
Adolescent
endocrine system diseases
T-Lymphocytes
Endocrinology
Diabetes and Metabolism
medicine.medical_treatment
Prohormone
Epitopes
T-Lymphocyte
digestive system
Antibodies
Endocrinology
Diabetes mellitus
Internal medicine
Internal Medicine
medicine
Humans
Insulin
Receptor-Like Protein Tyrosine Phosphatases
Class 8
Autoantibodies
Proinsulin
Protein Tyrosine Phosphatase
Non-Receptor Type 1
Type 1 diabetes
biology
Glutamate Decarboxylase
business.industry
Histocompatibility Testing
Autoantibody
nutritional and metabolic diseases
medicine.disease
Peptide Fragments
Diabetes Mellitus
Type 1
Immunology
biology.protein
Protein Tyrosine Phosphatases
Antibody
business
hormones
hormone substitutes
and hormone antagonists
medicine.drug
Zdroj: Diabetes/Metabolism Research and Reviews. 19:52-59
ISSN: 1520-7560
1520-7552
DOI: 10.1002/dmrr.332
Popis: Background: Type 1 diabetes (T1D) is an autoimmune disease characterized by immunity against pancreatic islet-derived proteins. The object of this study was to measure antibody and T-cell responses against proinsulin (PI), an islet-derived protein, and to map its dominant T-cell epitopes. Methods: Antibody responses to proinsulin, insulin, glutamic acid decarboxylase (GAD), protein tyrosine phosphatase IA-2 and islet-cell antigen were measured in 116 newly diagnosed diabetic subjects aged 16 to 40 years. T-cell proliferative responses to proinsulin and proinsulin peptides were measured in 33 of these diabetic subjects and in 21 healthy control subjects. Results: 22% of diabetic subjects but no control subjects expressed antibodies to proinsulin. A strong correlation existed between antibody levels to proinsulin and insulin within diabetic subjects. Similar proportions of diabetic (12%) and healthy (9.5%) subjects displayed T-cell responses to proinsulin. There was no correlation between antibody and T-cell responses to proinsulin within subjects. Amino acid region 56 to 72 was identified as the major T-cell epitope of proinsulin, though significant responses to region 14 to 37 were also present. Conclusion: Elevated proinsulin autoantibodies in diabetic subjects confirm proinsulin is an important autoantigen in type 1 diabetes. Though elevated cellular immunity to proinsulin protein was not detected, two dominant T-cell epitopes of proinsulin were identified that span the C-peptide and insulin junctions. Immunity to proinsulin was lower than that reported for childhood-onset type 1 diabetes and we propose that, like insulin, proinsulin may be targeted less frequently in adulthood.
Databáze: OpenAIRE
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