Open AccessA novel antibody for the detection of alternatively spliced secreted KLOTHO isoform in human plasma
Author(s) -
Shreyas Jadhav,
Sudipta Tripathi,
Anil Chandrekar,
Sushrut S. Waikar,
LiLi Hsiao
Publication year - 2021
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0245614
Subject(s) - klotho , gene isoform , alternative splicing , transmembrane protein , biology , antibody , microbiology and biotechnology , extracellular , biomarker , immunology , biochemistry , receptor , gene , endocrinology , kidney
αKlotho is primarily known to express as a transmembrane protein. Proteolytic cleavage results in shedding of the extracellular domain which enters systemic circulation. A truncated form of αKlotho resulting from alternative splicing of the αKLOTHO transcript exists and is believed to be secreted, thereby also entering systemic circulation. Existing ELISA methods fail to distinguish between the two circulating isoforms resulting in inconsistencies in assessing circulating αKlotho levels. We have exploited a unique 15aa peptide sequence present in the alternatively spliced secreted isoform to generate an antibody and show that it is able to specifically detect only the secreted Klotho isoform in human plasma. This finding will facilitate in distinguishing the levels of different circulating Klotho isoforms in health and disease and enhance their potential to serve as a biomarker for CKD and other conditions.