For application in indirect ELISA for coating procedure.
Purity
> 90%
Format
Lyophilized
Buffer
20mM PB, pH7.4
Preservative
None
Storage
2-8°C short term, -20°C long term
Introduction
Type 1 diabetes, also known as insulin-dependent diabetes mellitus (IDDM), results from a chronic autoimmune destruction of the insulin-secreting pancreatic beta cells, probably initiated by exposure of genetically susceptible host to an environmental agent. Autoimmune destruction of beta cells is thought to be completely asymptomatic until 80 -90% of the cells are lost. This process may take years to complete and may occur at any time. During the preclinical phase, this autoimmune process is marked by circulating autoantibodies to beta cell antigens. These autoantibodies are present years before the onset of type 1 diabetes and prior to clinical symptoms. Early studies utilized the immunofluorescence test for islet-cell antibodies (ICA), which has been difficult to standardize and is now replaced by a combination of several radioimmunoassays for antibodies against specific beta cell antigens, such as insulin (IAA), glutamic acid decarboxylase (GAD) and tyrosine phosphatase ICA 512 (IA2). IA2, a member of the protein tyrosine phosphatases family is localized in the dense granules of pancreatic beta cells and the second defined recombinant islet cell antigen. IA2 shares sequence identity with the islet cell antigen 512. The higher frequency of antibodies to IA2 is explained by the presence of autoantibodies directed to the COOH terminus of IA2 which is lacking in the ICA512 molecule. IA2 autoantibodies are present in the majority of individuals with new-onset type 1 diabetes and in individuals in the pre-diabetic phase of the disease. The appearance of autoantibodies to IA2 seems to be correlated with the rapid progression to overt type 1 diabetes. The combination of tests for GAD65 and IA2 autoantibodies is highly relevant for risk assessment of type 1 diabetes in children and adolescence. The screening for GAD65 and IA2 autoantibodies detect more than 90 % of subjects at risk for type 1 diabetes and may, therefore, possess the potential to replace ICA technique.
Keywords
IA-2; PTPRN; Islet Antigen-2; Type 1 Diabetes; T1D; Diabetes
Citations
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Background
Diabetes mellitus is a chronic metabolic disease characterized by hyperglycemia. Long-term untreated or uncontrolled hyperglycemic patients may develop microvascular and macrovascular complications. Therefore, early detection or prediction of the onset of diabetes and timely intervention with appropriate medical measures can delay the onset of diabetes-related diseases. Type 1 diabetes (T1D) is characterized by destruction of pancreatic β cells, resulting in absolute insulin deficiency. T1D is an autoimmune disease in which antibodies against a variety of islet autoantigens can be present in patients with lymphocytic infiltration around and within the islets. Based on the presence or absence of anti-islet autoantibodies in peripheral blood, T1D can be classified as immune-mediated or idiopathic. Anti-islet autoantibodies appear before the onset of the disease and are important biomarkers for the prediction and diagnosis of T1D. The anti-islet autoantibodies discovered so far include islet cell antibodies (ICA), insulin autoantibodies (IAA), anti-glutamic acid decarboxylase (GAD) antibodies, and tyrosine phosphatase-like protein IA-2 autoantibodies (IA-2A).
IA-2A is used for diagnosis, pathologic analysis and prediction of T1D. IA-2, or ICA512, is a transmembrane glycoprotein of the protein tyrosine phosphatase (PTP) family consisting of 979 amino acids that is expressed in the membranes of insulin-secreting granules of pancreatic β-cells and regulates insulin-secreting granule content and pancreatic β-cell growth. The IA-2 amino acid sequence contains luminal, transmembrane, and cytoplasmic domains, and the cytoplasmic domain contains the PTP core sequence, but its expressed proteins do not exhibit protein tyrosine phosphatase activity. IA-2A can be detected in patients with prediabetes and new-onset T1D with a seropositivity rate of 60-70%. The recognition epitopes of IA-2A are mainly localized to the cytoplasmic domain, with approximately 95% of IA-2A-positive prediabetic and T1D patients recognizing the PTP-like domain, and only 5% of sera reacting with the luminal domain. Another important epitope is located in the IA-2 juxtamembrane domain (IA-2JM) of amino acids 601-629. It was found that the age of onset was significantly higher in patients reacting only to IA-2JMA than in those reacting to the PTP-like structural domain, suggesting that autoantibody recognition of the IA-2 epitope in autoimmune diabetic patients is associated with age of onset, which may reflect the intensity of the β-cell destruction process.
Figure 1. Illustration of antigenic epitopes recognized by T1D sera in IA-2 (Source: Kawasaki E. 2023)
Early detection of anti-islet autoantibodies is clinically important for early diagnosis and appropriate treatment, due to the fact that autoantibody levels of anti-islet autoantibodies decrease with disease duration and may become negative. The current novel autoantibody assay detects multiple autoantibodies at the same time, and has the advantages of high sensitivity, high specificity, and large test sample size, making it suitable for large-scale population screening for T1D.
Alternative Names
Human tyrosine phosphatase-like protein IA-2 Human tyrosine phosphatase ICA512 Human islet antigen 2
References
1. Kawasaki E. Anti-Islet Autoantibodies in Type 1 Diabetes. Int J Mol Sci. 2023 Jun 11;24(12):10012.
2. Fyvie MJ, et al. The importance of biomarker development for monitoring type 1 diabetes progression rate and therapeutic responsiveness. Front Immunol. 2023 May 15;14:1158278
Q: Thank you for sending us the IA2. It does seem to be reactive with our anti-IA2 antibodies.
On another note, in your quality control experiments, have you noticed this protein to be quite sticky? I'm noticing low recovery rates in our Amicon ultracentrifuge filter and Thermo Zeba filter. Are these known to be hydrophobic and stick to tube walls? Just curious, no worries if this is beyond the scope of your domain.
A: Regarding the low recovery rates you're seeing with the Amicon ultra-centrifugal filters and the Thermo Zeba spin columns: our R&D team has not observed that this protein is particularly hydrophobic or prone to sticking to tube walls under routine QC conditions. However, individual labware and buffer combinations can sometimes produce different results. A few quick checks that often help: Make sure the vial is fully thawed and visually inspected for any precipitate. If you see particles, gently pipette up and down (avoid foaming) and give it a brief low-speed spin before use. If the sample is clear but still "sticky," try a modest dilution (1:2–1:4) in the same PBS buffer and repeat your concentration step to see whether recovery improves. For concentrating this particular protein, we have generally obtained higher yields with either PEG precipitation followed by gentle re-solubilization or lyophilization instead of ultrafiltration.
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The aim of the study. To demonstrate the role of laparovaginal surgery as minimal invasive method in early cervical cancer. Methods. We operated 44 patients between 2006 and 2011, with cervical cancer IA2-IB1 stages in private practice. In 21 cases we performed radical trachelectomy with sentinel node sampling and in 23 cases radical vaginal hysterectomy (Schauta Stoeckel) with laparoscopic pelvic lymphadenectomy. The deep surgical technique is further presented. Results. This study presents the data concerning operative time, blood loss, and perioperative complication. Conclusion. Using the combination of vaginal and laparoscopic surgery we offer to the surgeon the possibility to conserve the anatomy and function in early cervical cancer. This study is relevant as it presents a significant number of patients with radical trachelectomy - a procedure not very frequently reported in the literature. The authors consider it significant also in regard with the 100% survival rate.
Distinct Clinicopathologic Characteristics and Prognosis Based on the Presence of Ground Glass Opacity Component in Clinical Stage IA Lung Adenocarcinoma
Introduction: We evaluated differences in the clinicopathologic characteristics and prognosis based on the presence of ground glass opacity (GGO) components in small-sized lung adenocarcinoma. Methods: We retrospectively investigated 634 lung adenocarcinomas classed as c-stage IA in the eighth edition TNM classification. Staging was defined according to the solid component size measured by thin-section computed tomography. All tumors were grouped into either a GGO or solid group, based on the presence of a GGO component. Results: Of the cases, 215 (34%) were classed as c-stage IA1 (T1mi: 88, T1a-GGO: 102, T1a-solid: 25), 255 (40%) as c-stage IA2 (T1b-GGO: 122, T1b-solid: 133), and 164 (26%) as c-stage IA3 (T1c-GGO: 44, T1c-solid: 120). Among the 546 c-stage IA cases excluding the T1mi lesions, Cox regression analysis revealed that presence of GGO was an independently significant prognosticator (p = 0.024). The result was validated in 494 c-stage IA lung adenocarcinomas with a nonpredominant GGO component, showing the presence of GGO as a significant prognosticator (p = 0.048). When we evaluated the prognostic impact of GGOpresence in each clinical stage, the 5-year overall survival (OS) was significantly different between the GGO and solid groups (IA1: 97.8% versus 86.6%, p = 0.026; IA2: 89.3% versus 75.2%, p = 0.007; IA3: 88.5% versus 62.3%, p = 0.003). Furthermore, the 5-year overall survival b was distinct in parallel similar pathologic findings when comparing a lepidic versus an invasive component (IA1: 97.9% versus 85.6%, p = 0.031; IA2: 86.1% versus 69.4%, p = 0.007; IA3: 77.5% versus 55.8%, p < 0.001). Conclusions: Clinicopathologic and oncologic outcomes were disparate based on the presence of a GGO component in the eighth edition TNM classification of c-stage IA lung adenocarcinoma. (C) 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.
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Figure 1. Illustration of antigenic epitopes recognized by T1D sera in IA-2
