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Related Experiment Video

Updated: Jul 20, 2025

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Differences in the Circulating Proteome in Individuals with versus without Sickle Cell Trait.

Yanwei Cai1, Nora Franceschini2, Aditya Surapaneni3,4

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Clinical Journal of the American Society of Nephrology : CJASN
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Summary

Sickle cell trait is linked to kidney disease risk through specific proteins. This study identified key protein biomarkers associated with sickle cell trait and kidney failure in Black individuals.

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Area of Science:

  • Nephrology
  • Genetics
  • Proteomics

Background:

  • Sickle cell trait (SCT) affects millions globally, particularly those with African ancestry.
  • While often considered benign, SCT is increasingly linked to kidney disease and failure.
  • The biological mechanisms connecting SCT to kidney damage are not fully understood.

Purpose of the Study:

  • To investigate the proteomic differences associated with sickle cell trait.
  • To identify potential biomarkers linking sickle cell trait to kidney disease.
  • To explore the pathobiology of sickle cell trait in relation to kidney function.

Main Methods:

  • Proteomic profiling of 1285 proteins in plasma samples from 592 Black participants with SCT and matched controls.
  • Utilized Olink Explore platform for initial proteomic analysis.
  • Replicated findings in independent cohorts using an aptamer-based proteomic platform (SomaScan).

Main Results:

  • Identified 35 proteins significantly associated with sickle cell trait after multiple testing correction.
  • Validated associations in independent cohorts, revealing proteins linked to kidney injury (e.g., KIM-1, UMOD), hemolysis (e.g., EPO, HMOX1), and inflammation (e.g., MCP-1).
  • A protein risk score derived from these biomarkers predicted incident kidney failure in individuals with SCT.

Conclusions:

  • Established a link between sickle cell trait and specific plasma proteins involved in hemolysis, kidney injury, and inflammation.
  • Validated these protein associations across multiple cohorts.
  • Highlighted the potential of identified proteins as biomarkers for kidney disease risk in sickle cell trait carriers.