TITLE:
Identification of a Native Novel Oncolytic Immunoglobulin on Exfoliated Colon Epithelial Cells: A Bispecific Heterodimeric Chimera of IgA/IgG*
AUTHORS:
George P. Albaugh, Sudhir K. Dutta, Vasantha Iyengar, Samina Shami, Althaf Lohani, Eduardo Sainz, George Kessie, Prasanna Nair, Sara Lagerholm, Alka Kamra, J.-H. Joshua Chen, Shilpa Kalavapudi, Rakesh Vinayek, Robert Shores, Laila E. Phillips, Ram Nair, Padmanabhan P. Nair
KEYWORDS:
Colon Epithelial Cells, CXCR-4, IgA/IgG Chimeric Immunoglobulin Heterodimer, COX-2, LGR-5, Musashi-1, Dedifferentiation, Cellular Engraftment, Oncoly-sis, Gastrointestinal Progenitor Stem Cells (GIP-C)
JOURNAL NAME:
Open Journal of Preventive Medicine,
Vol.10 No.6,
June
30,
2020
ABSTRACT: Understanding the nature of cell surface markers on exfoliated colonic cells is a crucial step in establishing criteria for a normally functioning mucosa. We have found that colonic cells isolated from stool samples (SCSR-010 Fecal Cell Isolation Kit, NonInvasive Technologies, Elkridge, MD), preserved at room temperature for up to one week, with viability of >85% and low levels of apoptosis (8% - 10%) exhibit two distinct cell size subpopulations, in the 2.5 μM - 5.0 μM and 5.0 μM - 8.0 μM range. In addition to IgA, about 60% of the cells expressed a novel heterodimeric IgA/IgG immunoglobulin that conferred a broad-spectrum cell mediated cytotoxicity against tumor cells. In a cohort of 58 subjects the exclusive absence of this immunoglobulin in two African-Americans was suggestive of a germline deletion. Serial cultures in stem cell medium retained the expression of this heterodimer. Since a majority of the cystic cells expressed the stem cell markers Lgr5 and Musashi-1 we termed these cells as gastrointestinal progenitor stem cells (GIP-C**). CXCR-4, the cytokine co-receptor for HIV was markedly expressed. These cells also expressed CD20, IgA, IgG, CD45, and COX-2. We assume that they originated from mature columnar epithelium by dedifferentiation. Our observations indicate that we have a robust noninvasive method to study mucosal pathophysiology and a direct method to create a database for applications in regenerative medicine.