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

alpha 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 alpha Klotho resulting from alternative splicing of the alpha 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 alpha 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.

Automated summary

The study identified two circulating isoforms of alpha Klotho and developed an antibody using a unique 15aa peptide sequence to specifically detect the secreted isoform in human plasma. This finding will enhance the potential of alpha Klotho isoforms as biomarkers for CKD and other conditions by facilitating the distinguishing of their levels in circulation.