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Serum titres of anti‐glutamic acid decarboxylase‐65 and anti‐IA‐2 autoantibodies are associated with different immunoregulatory milieu in newly diagnosed type 1 diabetes patients

Andrade Lima Gabbay, M. ; Sato, M. N. ; Duarte, A. J. S. ; Dib, S. A.

Clinical and experimental immunology, 2012-04, Vol.168 (1), p.60-67 [Periódico revisado por pares]

Oxford, UK: Blackwell Publishing Ltd

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Título:
Serum titres of anti‐glutamic acid decarboxylase‐65 and anti‐IA‐2 autoantibodies are associated with different immunoregulatory milieu in newly diagnosed type 1 diabetes patients
Autor: Andrade Lima Gabbay, M. ; Sato, M. N. ; Duarte, A. J. S. ; Dib, S. A.
Assuntos: Adolescent ; Analytical, structural and metabolic biochemistry ; Autoantibodies ; Autoantibodies - blood ; Autoantibodies - immunology ; Beta cells ; Biological and medical sciences ; Chemokines ; Chemokines - blood ; Child ; CXCL10 protein ; cytokine ; Cytokines ; Cytokines - blood ; Data processing ; Diabetes mellitus ; Diabetes Mellitus, Type 1 - blood ; Diabetes Mellitus, Type 1 - genetics ; Diabetes Mellitus, Type 1 - immunology ; Diabetes. Impaired glucose tolerance ; Endocrine pancreas. Apud cells (diseases) ; Endocrinopathies ; Etiopathogenesis. Screening. Investigations. Target tissue resistance ; Female ; Fundamental and applied biological sciences. Psychology ; Genetic Predisposition to Disease ; Genotype ; Glutamate Decarboxylase - genetics ; Glutamate Decarboxylase - immunology ; Glutamic acid ; Histocompatibility antigen HLA ; HLA-DR3 Antigen - genetics ; HLA-DR4 Antigen - genetics ; Humans ; Immunoregulation ; Inflammation ; Insulin-Secreting Cells - immunology ; Interleukin 10 ; Interleukin 12 ; Interleukin 6 ; Interleukin 8 ; Islet cells ; Leukocytes ; Lymphocytes T ; Male ; Medical sciences ; Monocyte chemoattractant protein 1 ; Original ; Pancreas ; pancreatic autoantibodies ; Polymorphism, Single Nucleotide ; Protein Tyrosine Phosphatase, Non-Receptor Type 22 - genetics ; Protein-tyrosine-phosphatase ; regulatory T cells ; Tumor necrosis factor- alpha ; type 1 diabetes
É parte de: Clinical and experimental immunology, 2012-04, Vol.168 (1), p.60-67
Notas: Senior author
sergio.dib@unifesp.br
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Senior author: sergio.dib@unifesp.br
Descrição: Summary Several studies correlated genetic background and pancreatic islet‐cell autoantibody status (type and number) in type 1A diabetes mellitus (T1AD), but there are no data evaluating the relationship among these markers with serum cytokines, regulatory T cells and β cell function. This characterization has a potential importance with regard to T1AD patients' stratification and follow‐up in therapeutic prevention. In this study we showed that peripheral sera cytokines [interleukin (IL)‐12, IL‐6, II‐1β, tumour necrosis factor (TNF)‐α, IL‐10] and chemokines (CXCL10, CXCL8, CXCL9, CCL2) measured were significantly higher in newly diagnosed T1AD patients when compared to healthy controls (P < 0·001). Among T1AD, we found a positive correlation between CXCL10 and CCL‐2 (r = 0·80; P = 0·000), IL‐8 and TNF‐α (r = 0·60; P = 0·000); IL‐8 and IL‐12 (r = 0·57; P = 0·001) and TNF‐α and IL‐12 (r = 0·93; P = 0·000). Glutamic acid decarboxylase‐65 (GAD‐65) autoantibodies (GADA) were associated negatively with CXCL10 (r = −0·45; P = 0·011) and CCL2 (r = −0·65; P = 0·000), while IA‐2A showed a negative correlation with IL‐10 (r = −0·38; P = 0·027). Human leucocyte antigen (HLA) DR3, DR4 or DR3/DR4 and PTPN22 polymorphism did not show any association with pancreatic islet cell antibodies or cytokines studied. In summary, our results revealed that T1AD have a proinflammatory cytokine profile compared to healthy controls and that IA‐2A sera titres seem to be associated with a more inflammatory peripheral cytokine/chemokine profile than GADA. A confirmation of these data in the pre‐T1AD phase could help to explain the mechanistic of the well‐known role of IA‐2A as a more specific marker of beta‐cell damage than GADA during the natural history of T1AD.
Editor: Oxford, UK: Blackwell Publishing Ltd
Idioma: Inglês

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Serum titres of anti‐glutamic acid decarboxylase‐65 and anti‐IA‐2 autoantibodies are associated with different immunoregulatory milieu in newly diagnosed type 1 diabetes patients

Andrade Lima Gabbay, M. ; Sato, M. N. ; Duarte, A. J. S. ; Dib, S. A.

Oxford, UK: Blackwell Publishing Ltd

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