A combined biomarker and clinical panel for chronic graft versus host disease diagnosis

Joseph Pidala; Tara K. Sigdel; Anyou Wang; Sue Hsieh; Yoshi Inamoto; Paul J. Martin; Mary E.D. Flowers; John A. Hansen; Stephanie J. Lee; Minnie M. Sarwal

doi:10.1002/cjp2.58

A combined biomarker and clinical panel for chronic graft versus host disease diagnosis

Joseph Pidala, Tara K. Sigdel, Anyou Wang, Sue Hsieh, Yoshi Inamoto, Paul J. Martin, Mary E.D. Flowers, John A. Hansen, Stephanie J. Lee, Minnie M. Sarwal

Research output: Contribution to journal › Article › peer-review

22 Citations (Scopus)

Abstract

Whilst many chronic graft versus host disease (cGVHD) biomarkers have been previously reported, few have been verified in an independent cGVHD cohort. We aimed to verify the diagnostic accuracy of previously reported markers of cGVHD in a multi-centre Chronic GVHD Consortium. A total of 42 RNA and 18 protein candidate biomarkers were assessed amongst 59 cGVHD cases and 33 matched non-GVHD controls. Total RNA was isolated from PBMC, and RNA markers were quantified using PCR. Serum protein markers were quantified using ELISA. A combined 3 RNA biomarker (IRS2, PLEKHF1 and IL1R2) and 2 clinical variables (recipient CMV serostatus and conditioning regimen intensity) panel accurately (AUC 0.81) segregated cGVHD cases from controls. Other studied RNA and protein markers were not confirmed as accurate cGVHD diagnostic biomarkers. The studied markers failed to segregate higher risk cGVHD (per overall NIH 0-3 score, and overlap versus classic cGVHD status). These data support the need for multiple independent verification studies for the ultimate clinical application of cGVHD diagnostic biomarkers.

Original language	English
Pages (from-to)	3-16
Number of pages	14
Journal	Journal of Pathology: Clinical Research
Volume	3
Issue number	1
DOIs	https://doi.org/10.1002/cjp2.58
Publication status	Published - 01-01-2017
Externally published	Yes

All Science Journal Classification (ASJC) codes

Pathology and Forensic Medicine

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10.1002/cjp2.58

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title = "A combined biomarker and clinical panel for chronic graft versus host disease diagnosis",

abstract = "Whilst many chronic graft versus host disease (cGVHD) biomarkers have been previously reported, few have been verified in an independent cGVHD cohort. We aimed to verify the diagnostic accuracy of previously reported markers of cGVHD in a multi-centre Chronic GVHD Consortium. A total of 42 RNA and 18 protein candidate biomarkers were assessed amongst 59 cGVHD cases and 33 matched non-GVHD controls. Total RNA was isolated from PBMC, and RNA markers were quantified using PCR. Serum protein markers were quantified using ELISA. A combined 3 RNA biomarker (IRS2, PLEKHF1 and IL1R2) and 2 clinical variables (recipient CMV serostatus and conditioning regimen intensity) panel accurately (AUC 0.81) segregated cGVHD cases from controls. Other studied RNA and protein markers were not confirmed as accurate cGVHD diagnostic biomarkers. The studied markers failed to segregate higher risk cGVHD (per overall NIH 0-3 score, and overlap versus classic cGVHD status). These data support the need for multiple independent verification studies for the ultimate clinical application of cGVHD diagnostic biomarkers.",

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year = "2017",

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doi = "10.1002/cjp2.58",

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AU - Pidala, Joseph

AU - Sigdel, Tara K.

AU - Wang, Anyou

AU - Hsieh, Sue

AU - Inamoto, Yoshi

AU - Martin, Paul J.

AU - Flowers, Mary E.D.

AU - Hansen, John A.

AU - Lee, Stephanie J.

AU - Sarwal, Minnie M.

PY - 2017/1/1

Y1 - 2017/1/1

N2 - Whilst many chronic graft versus host disease (cGVHD) biomarkers have been previously reported, few have been verified in an independent cGVHD cohort. We aimed to verify the diagnostic accuracy of previously reported markers of cGVHD in a multi-centre Chronic GVHD Consortium. A total of 42 RNA and 18 protein candidate biomarkers were assessed amongst 59 cGVHD cases and 33 matched non-GVHD controls. Total RNA was isolated from PBMC, and RNA markers were quantified using PCR. Serum protein markers were quantified using ELISA. A combined 3 RNA biomarker (IRS2, PLEKHF1 and IL1R2) and 2 clinical variables (recipient CMV serostatus and conditioning regimen intensity) panel accurately (AUC 0.81) segregated cGVHD cases from controls. Other studied RNA and protein markers were not confirmed as accurate cGVHD diagnostic biomarkers. The studied markers failed to segregate higher risk cGVHD (per overall NIH 0-3 score, and overlap versus classic cGVHD status). These data support the need for multiple independent verification studies for the ultimate clinical application of cGVHD diagnostic biomarkers.

AB - Whilst many chronic graft versus host disease (cGVHD) biomarkers have been previously reported, few have been verified in an independent cGVHD cohort. We aimed to verify the diagnostic accuracy of previously reported markers of cGVHD in a multi-centre Chronic GVHD Consortium. A total of 42 RNA and 18 protein candidate biomarkers were assessed amongst 59 cGVHD cases and 33 matched non-GVHD controls. Total RNA was isolated from PBMC, and RNA markers were quantified using PCR. Serum protein markers were quantified using ELISA. A combined 3 RNA biomarker (IRS2, PLEKHF1 and IL1R2) and 2 clinical variables (recipient CMV serostatus and conditioning regimen intensity) panel accurately (AUC 0.81) segregated cGVHD cases from controls. Other studied RNA and protein markers were not confirmed as accurate cGVHD diagnostic biomarkers. The studied markers failed to segregate higher risk cGVHD (per overall NIH 0-3 score, and overlap versus classic cGVHD status). These data support the need for multiple independent verification studies for the ultimate clinical application of cGVHD diagnostic biomarkers.

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A combined biomarker and clinical panel for chronic graft versus host disease diagnosis

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