title: 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.
abstract: 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.
authors.affiliation: Diabetes Center, Endocrinology Division, Department of Medicine, Federal University of São Paulo-Immunology Laboratory, Rua Pedro de Toledo 781/12, São Paulo, SP, Brazil. monicagabbay@gmail.com
authors.forename: M Andrade Lima
authors.initials: MA
authors.lastname: Gabbay
authors.forename: M N
authors.initials: MN
authors.lastname: Sato
authors.forename: A J S
authors.initials: AJ
authors.lastname: Duarte
authors.forename: S A
authors.initials: SA
authors.lastname: Dib
mesh_terms: D000293:Adolescent; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D018925:Chemokines / Q000097:blood; D002648:Child; D016207:Cytokines / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000235:genetics / Q000276:immunology*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005968:Glutamate Decarboxylase / Q000235:genetics / Q000276:immunology*; D015803:HLA-DR3 Antigen / Q000235:genetics; D015804:HLA-DR4 Antigen / Q000235:genetics; D006801:Humans; D050417:Insulin-Secreting Cells / Q000276:immunology; D008297:Male; D020641:Polymorphism, Single Nucleotide; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000235:genetics
chemical_list: D001323:Autoantibodies; D018925:Chemokines; D016207:Cytokines; D015803:HLA-DR3 Antigen; D015804:HLA-DR4 Antigen; C096322:ICA512 autoantibody; C516765:PTPN22 protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22; D005968:Glutamate Decarboxylase