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A novel antibody for the detection of alternatively spliced secreted KLOTHO isoform in human plasma.

ABSTRACT: ?Klotho 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 ?Klotho resulting from alternative splicing of the ?KLOTHO 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 ?Klotho 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.

SUBMITTER: Jadhav S

PROVIDER: S-EPMC7822350 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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A novel antibody for the detection of alternatively spliced secreted KLOTHO isoform in human plasma.

Jadhav Shreyas S Tripathi Sudipta S Chandrekar Anil A Waikar Sushrut S SS Hsiao Li-Li LL

PloS one 20210122 1

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 ...[more]

PMID: 33481901

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