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Errors in data interpretation from genetic variation of human analytes.


ABSTRACT: In recent years, the extent of our vulnerability to misinterpretation due to poorly characterized reagents has become an issue of great concern. Antibody reagents have been identified as a major source of error, contributing to the "reproducibility crisis." In the current report, we define an additional dimension of the crisis; in particular, we define variation of the targets being analyzed. We report that natural variation in the immunoglobulin "constant" region alters the reactivity with commonly used subtype-specific anti-IgG reagents, resulting in cross-reactivity of polyclonal regents with inappropriate targets and blind spots of monoclonal reagents for desired targets. This raises the practical concern that numerous studies characterizing IgG subtypes in human disease may contain errors due to such previously unappreciated defects. These studies also focus attention on the broader concern that genetic variation may affect the performance of any laboratory or research test that uses antibodies for detection.

SUBMITTER: Howie HL 

PROVIDER: S-EPMC5499359 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Errors in data interpretation from genetic variation of human analytes.

Howie Heather L HL   Delaney Meghan M   Wang Xiaohong X   Er Lay See LS   Kapp Linda L   Lebedev Jenna N JN   Zimring James C JC  

JCI insight 20170706 13


In recent years, the extent of our vulnerability to misinterpretation due to poorly characterized reagents has become an issue of great concern. Antibody reagents have been identified as a major source of error, contributing to the "reproducibility crisis." In the current report, we define an additional dimension of the crisis; in particular, we define variation of the targets being analyzed. We report that natural variation in the immunoglobulin "constant" region alters the reactivity with comm  ...[more]

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