Candidate Biomarkers for Targeting in Type 1 Diabetes; A Bioinformatic Analysis of Pancreatic Cell Surface Antigens

Document Type : Original Article

Authors

1 Department of Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran

2 Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran

3 National Cell Bank of Iran, Pasteur Institute of Iran, Tehran, Iran

4 Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran

5 Advanced Therapy Medicinal Product Technology Development Center (ATMP-TDC), Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran

Abstract

Objective: Type 1 diabetes (T1Ds) is an autoimmune disease in which the immune system invades and destroys
insulin-producing cells. Nevertheless, at the time of diagnosis, about 30-40% of pancreatic beta cells are healthy and
capable of producing insulin. Bi-specific antibodies, chimeric antigen receptor regulatory T cells (CAR-Treg cells), and
labeled antibodies could be a new emerging option for the treatment or diagnosis of type I diabetic patients. The aim
of the study is to choose appropriate cell surface antigens in the pancreas tissue for generating an antibody for type I
diabetic patients.
Materials and Methods: In this bioinformatics study, we extracted pancreas-specific proteins from two large
databases; the Human Protein Atlas (HPA) and Genotype-Tissue Expression (GTEx) Portal. Pancreatic-enriched
genes 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 of
selected antigens. We explored the function of candidate antigens by using the GeneCards database to evaluate the
potential 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 encoded
plasma membrane proteins that have high expression in the microarray (GEO) dataset. Our results introduced four
structural 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 therapy
scopes for type I diabetes.

Keywords

Main Subjects

References

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