Cell Journal (Jan 2024)
Candidate Biomarkers for Targeting in Type 1 Diabetes; A Bioinformatic Analysis of Pancreatic Cell Surface Antigens
Abstract
Objective: Type 1 diabetes (T1Ds) is an autoimmune disease in which the immune system invades and destroysinsulin-producing cells. Nevertheless, at the time of diagnosis, about 30-40% of pancreatic beta cells are healthy andcapable of producing insulin. Bi-specific antibodies, chimeric antigen receptor regulatory T cells (CAR-Treg cells), andlabeled antibodies could be a new emerging option for the treatment or diagnosis of type I diabetic patients. The aimof the study is to choose appropriate cell surface antigens in the pancreas tissue for generating an antibody for type Idiabetic patients.Materials and Methods: In this bioinformatics study, we extracted pancreas-specific proteins from two largedatabases; the Human Protein Atlas (HPA) and Genotype-Tissue Expression (GTEx) Portal. Pancreatic-enrichedgenes were chosen and narrowed down by Protter software for the investigation of accessible extracellular domains.The immunohistochemistry (IHC) data of the protein atlas database were used to evaluate the protein expression ofselected antigens. We explored the function of candidate antigens by using the GeneCards database to evaluate thepotential dysfunction or activation/hyperactivation of antigens after antibody binding.Results: The results showed 429 genes are highly expressed in the pancreas tissue. Also, eighteen genes encodedplasma membrane proteins that have high expression in the microarray (GEO) dataset. Our results introduced fourstructural proteins, including NPHS1, KIRREL2, GP2, and CUZD1, among all seventeen candidate proteins.Conclusion: The presented antigens can potentially be used to produce specific pancreatic antibodies that guide CARTreg,bi-specific, or labeling molecules to the pancreas for treatment, detection, or other molecular targeted therapyscopes for type I diabetes.
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