Abstract
Chronic graft-versus-host disease (cGVHD) remains one of the most significant long-term complications after allogeneic blood and marrow transplantation. Diagnostic biomarkers for cGVHD are needed for early diagnosis and may guide identification of prognostic markers. No cGVHD biomarker has yet been validated for use in clinical practice. We evaluated both previously known markers and performed discovery-based analysis for cGVHD biomarkers in a 2 independent test sets (total of 36 cases ≤1 month from diagnosis and 31 time-matched controls with no cGVHD). On the basis of these results, 11 markers were selected and evaluated in 2 independent replication cohorts (total of 134 cGVHD cases and 154 controls). cGVHD cases and controls were evaluated for several clinical covariates, and their impact on biomarkers was identified by univariate analysis. The 2 replications sets were relatively disparate in the biomarkers they replicated. Only sBAFF and, most consistently, CXCL10 were identified as significant in both replication sets. Other markers identified as significant in only 1 replication set included intercellular adhesion molecule 1 (ICAM-1), anti-LG3, aminopeptidase N, CXCL9, endothelin-1, and gelsolin. Multivariate analysis found that all covariates evaluated affected interpretation of the biomarkers. CXCL10 had an increased significance in combination with anti-LG3 and CXCL9, or inversely with CXCR3+ CD56bright natural killer (NK) cells. There was significant heterogeneity of cGVHD biomarkers in a large comprehensive evaluation of cGVHD biomarkers impacted by several covariates. Only CXCL10 strongly correlated in both replication sets. Future analyses for plasma cGVHD biomarkers will need to be performed on very large patient groups with consideration of multiple covariates.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 3082-3091 |
| Number of pages | 10 |
| Journal | Blood |
| Volume | 127 |
| Issue number | 24 |
| DOIs | |
| State | Published - Jun 16 2016 |
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ASJC Scopus subject areas
- Immunology
- Biochemistry
- Hematology
- Cell Biology
Cite this
Heterogeneity of chronic graft-versus-host disease biomarkers : Association with CXCL10 and CXCR3+ NK cells. / Kariminia, Amina; Holtan, Shernan G.; Ivison, Sabine; Rozmus, Jacob; Hebert, Marie Josée; Martin, Paul J.; Lee, Stephanie J.; Wolff, Daniel; Subrt, Peter; Abdossamadi, Sayeh; Sung, Susanna; Storek, Jan; Levings, Megan; Aljurf, Mahmoud; Arora, Mukta; Cutler, Corey; Gallagher, Geneviève; Kuruvilla, John; Lipton, Jeff; Nevill, Thomas J.; Newell, Laura; Panzarella, Tony; Pidala, Joseph; Popradi, Gizelle; Szwajcer, David; Tay, Jason; Toze, Cynthia L.; Walker, Irwin; Couban, Stephen; Storer, Barry E.; Schultz, Kirk R.
In: Blood, Vol. 127, No. 24, 16.06.2016, p. 3082-3091.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Heterogeneity of chronic graft-versus-host disease biomarkers
T2 - Association with CXCL10 and CXCR3+ NK cells
AU - Kariminia, Amina
AU - Holtan, Shernan G.
AU - Ivison, Sabine
AU - Rozmus, Jacob
AU - Hebert, Marie Josée
AU - Martin, Paul J.
AU - Lee, Stephanie J.
AU - Wolff, Daniel
AU - Subrt, Peter
AU - Abdossamadi, Sayeh
AU - Sung, Susanna
AU - Storek, Jan
AU - Levings, Megan
AU - Aljurf, Mahmoud
AU - Arora, Mukta
AU - Cutler, Corey
AU - Gallagher, Geneviève
AU - Kuruvilla, John
AU - Lipton, Jeff
AU - Nevill, Thomas J.
AU - Newell, Laura
AU - Panzarella, Tony
AU - Pidala, Joseph
AU - Popradi, Gizelle
AU - Szwajcer, David
AU - Tay, Jason
AU - Toze, Cynthia L.
AU - Walker, Irwin
AU - Couban, Stephen
AU - Storer, Barry E.
AU - Schultz, Kirk R.
PY - 2016/6/16
Y1 - 2016/6/16
N2 - Chronic graft-versus-host disease (cGVHD) remains one of the most significant long-term complications after allogeneic blood and marrow transplantation. Diagnostic biomarkers for cGVHD are needed for early diagnosis and may guide identification of prognostic markers. No cGVHD biomarker has yet been validated for use in clinical practice. We evaluated both previously known markers and performed discovery-based analysis for cGVHD biomarkers in a 2 independent test sets (total of 36 cases ≤1 month from diagnosis and 31 time-matched controls with no cGVHD). On the basis of these results, 11 markers were selected and evaluated in 2 independent replication cohorts (total of 134 cGVHD cases and 154 controls). cGVHD cases and controls were evaluated for several clinical covariates, and their impact on biomarkers was identified by univariate analysis. The 2 replications sets were relatively disparate in the biomarkers they replicated. Only sBAFF and, most consistently, CXCL10 were identified as significant in both replication sets. Other markers identified as significant in only 1 replication set included intercellular adhesion molecule 1 (ICAM-1), anti-LG3, aminopeptidase N, CXCL9, endothelin-1, and gelsolin. Multivariate analysis found that all covariates evaluated affected interpretation of the biomarkers. CXCL10 had an increased significance in combination with anti-LG3 and CXCL9, or inversely with CXCR3+ CD56bright natural killer (NK) cells. There was significant heterogeneity of cGVHD biomarkers in a large comprehensive evaluation of cGVHD biomarkers impacted by several covariates. Only CXCL10 strongly correlated in both replication sets. Future analyses for plasma cGVHD biomarkers will need to be performed on very large patient groups with consideration of multiple covariates.
AB - Chronic graft-versus-host disease (cGVHD) remains one of the most significant long-term complications after allogeneic blood and marrow transplantation. Diagnostic biomarkers for cGVHD are needed for early diagnosis and may guide identification of prognostic markers. No cGVHD biomarker has yet been validated for use in clinical practice. We evaluated both previously known markers and performed discovery-based analysis for cGVHD biomarkers in a 2 independent test sets (total of 36 cases ≤1 month from diagnosis and 31 time-matched controls with no cGVHD). On the basis of these results, 11 markers were selected and evaluated in 2 independent replication cohorts (total of 134 cGVHD cases and 154 controls). cGVHD cases and controls were evaluated for several clinical covariates, and their impact on biomarkers was identified by univariate analysis. The 2 replications sets were relatively disparate in the biomarkers they replicated. Only sBAFF and, most consistently, CXCL10 were identified as significant in both replication sets. Other markers identified as significant in only 1 replication set included intercellular adhesion molecule 1 (ICAM-1), anti-LG3, aminopeptidase N, CXCL9, endothelin-1, and gelsolin. Multivariate analysis found that all covariates evaluated affected interpretation of the biomarkers. CXCL10 had an increased significance in combination with anti-LG3 and CXCL9, or inversely with CXCR3+ CD56bright natural killer (NK) cells. There was significant heterogeneity of cGVHD biomarkers in a large comprehensive evaluation of cGVHD biomarkers impacted by several covariates. Only CXCL10 strongly correlated in both replication sets. Future analyses for plasma cGVHD biomarkers will need to be performed on very large patient groups with consideration of multiple covariates.
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U2 - 10.1182/blood-2015-09-668251
DO - 10.1182/blood-2015-09-668251
M3 - Article
VL - 127
SP - 3082
EP - 3091
JO - Blood
JF - Blood
SN - 0006-4971
IS - 24
ER -