Plasma proteins associated with chronic graft-versus-host disease organ involvement

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Abstract

BACKGROUND. Prior studies identified plasma proteins associated with chronic graft-versus-host disease (cGVHD). The goal of this cross-sectional study was to evaluate whether plasma biomarkers were associated with specific organ manifestations to help guide treatment choice. METHODS. Plasma proteins were measured in patients with cGVHD (n = 695) from Chronic GVHD Consortium studies. Correlations of plasma protein levels with individual organ involvement were tested with p≤0.05 considered significant after Benjamini-Hochberg adjustment and adjustment for five baseline clinical variables. RESULTS. Median time from cGVHD diagnosis to blood draw was 0.9 months (IQR 0.1–9.5). Donors were 50% HLA-matched unrelated, 32% matched related and the remainder were umbilical cord blood, haploidentical or mismatched unrelated donors. Methotrexate and calcineurin inhibitor acute GVHD (aGVHD) prophylaxis was used in 53% of patients. Overall, 326 (47%) had moderate and 244 (35%) had severe cGVHD with the following organ involvement at time of blood draw: skin (67%), mouth (60%), eye (49%), joint (34%), GI (31%), lung (23%), and liver (17%). After adjustment for batch effects and patient and transplant characteristics, fourteen plasma proteins were associated with organ involvement with independent AUCs of 0.7-0.8. All organs except eye were associated with at least one biomarker. However, no combination of plasma proteins improved model fit after adjusting for patient and transplant clinical variables. CONCLUSION. Correlations between plasma proteins and organ involvement were identified but are not actionable. Our future investigations will focus on more granular and immediately proximal determinants of cGVHD biology in both blood and tissue.

Authors

Stephanie J. Lee, Corey Cutler, Ningxin Ma, Timothy W. Randolph, George L. Chen, Joseph Pidala, Betty K. Hamilton, Carrie L. Kitko, Sally Arai, Najla El Jurdi, Lynn Onstad, Motoko Koyama, Catherine J. Lee, Sophie Paczesny, Geoffrey R. Hill