When used in combination with IA-2 antibody (IA-2A
), their predictivity for T1D and cost-effectivity compared to other antibody combinations is higher in "at risk" individuals, regardless of their age (15).
Third, we could not investigate other islet cell-associated autoantibodies such as autoantibodies to insulinoma-associated antigen (IA-2A
), insulin (IAA), islet cells (ICA), and zinc transporter 8 (ZnT8A).
Glutamic acid decarboxylase autoantibodies (GADA) and zinc transporter 8 autoantibodies (ZnT8A) analyzed by ELISA, insulin autoantibodies (IAA) analyzed by radioimmunoassay, islet antigen 2 autoantibodies (IA-2A
) analyzed by radiobinding assay, and islet cell antibodies (ICA) analyzed by immunofluorescence assay were all negative.
The two most common forms of DM are type 1 (T1DM) and type 2 (T2DM), with the former resulting from T-cell-mediated autoimmune destruction of b-cells of the pancreas, whereas the latter is characterised by insulin resistance with a non-autoimmune insulin secretory defect.1 Autoimmune DM is characterised by the presence of one or more islet-specific autoantibodies, including islet cell autoantibodies (ICA), insulin (IAA) and autoantibodies directed against the three major islet autoantigens - glutamic acid decarboxylase 65 (GADA), protein tyrosine phosphatase IA-2A
and its isoform IA-2b/phogrin (IA-2bA).2,3
Type 1A diabetes is characterized as the abnormal activation of the T cell mediated immune system, leading to an inflammatory response in islets as well as to a humoral response with production of autoantibodies to beta-cell antigens (ICA), insulin (IAA), glutamic acid decarboxylase (GADA), and the protein tyrosine phosphatase IA2 (IA-2A
It has been shown that at least 93% of the T1DM patients were autoantibody positive, based on autoantibodies against to GAD65 (GADA), IA-2 (IA-2A
), insulin (IAA), and ZnT8A.[sup] ZnT8A was found in nearly 30% other islet autoantibodies negative patients.[sup], According to our previous data, the diagnostic sensitivity of T1DM and LADA was 65.5% and 8.62%, respectively, based on GADA, IA-2A
, and ZnT8A.[sup], With the addition of ZnT8A to ICA, GADA, and IA-2A
increased the diagnostic sensitivity from 79.3% to 83.1% in newly diagnosed diabetic patients.[sup] Furthermore, ZnT8A is a valuable marker to differentiate clinical phenotypes in a proportion of patients with LADA,[sup] especially based on the detection of GADA and ZnT8A.[sup]
We divided them into 2 subgroups according to presence/absence of autoantibodies; 17 of them was classified as high risk (hr) FDRs, who were persistently positive for the presence of glutamic acid decarboxylase (GADA) and tyrosine phosphatase insulinoma antigen-2 (IA-2A
), while 34 FDRs were classified as low risk (lr) FDRs, negative for both autoantibodies.
Annual or biannual workshops [e.g., the Islet Autoantibody Standardization Program (IASP)] for islet autoantibody testing are available for IAA, GADA, IA-2A
, and ZnT8A.
Klinik kullanimdaki otoantikorlar "adacik hucresi sitoplaz-mik otoantikorlari (ICA)", "glutamik asid dekarboksilaza karsi antikorlar (Anti-GAD ya da GADA)", "insulin otoantikorlari (IAA)", "anti-tirozin fosfataz antikoru (ICA-512 veya IA-2A
; insulinoma ile iliskili otoantikorlar)", "anti-fogrin antikoru (IA-2[beta]; insulinoma ile iliskili 2[beta] otoantikor)" ve son zamanlarda tanimlanan "cinko transporter antikorlari (ZnT8A)" olmak uzere alti adettir.
With the exclusion of islet-cell cytoplasmic autoantibodies (ICA), glutamic acid decarboxylase (GAD) autoantibodies (GADA), insulinoma 2 (IA-2)-associated autoantibodies (IA-2A
), insulin autoantibodies (IAA), and zinc transporter 8 protein (ZnT8) islet autoantibody (ZnT8A), the other autoantibodies are difficult to measure and/or are not sufficiently sensitive or specific to warrant their use in present day studies of T1DM or its pathogenesis.
IA was defined as being positive in two or more measurements of autoantibodies indicative of the autoimmune response: glutamic acid decarboxylase (GADA); tyrosine phosphatase (IA-2A
); insulin autoantibodies (IAA) analysed at the three time points or being diagnosed with type 1 diabetes during the 5 year follow up period.
Although questioned repeatedly , current criteria for the diagnosis of LADA remain age at the onset, the presence of positive diabetes-associated autoantibodies--islet-cell cytoplasm autoantibodies (ICA), glutamic acid decarboxylase autoantibodies (GAD65A), insulinoma-associated-2 antibodies--tyrosine phosphatase associated (IA-2A
), zinc transporter 8 autoantibodies (ZnT8A); and satisfying glycemic control without insulin treatment for at least 6 months after diagnosis [5-8].