Plasma biomarkers and organ involvement in cGvHD

Results from a cross-sectional study, evaluating plasma protein biomarkers and their association with specific organ manifestations in patients with chronic graft-versus-host disease (cGvHD) were published in JCI Insight by Lee et al. Patients (N = 695) were included from three prospective, multicenter cohort studies run by the Chronic GvHD Consortium. Correlations were tested with p ≤ 0.05 considered significant following Benjamini–Hochberg adjustment and adjustment for five baseline clinical variables: patient age, sex, time between hematopoietic stem cell transplantation (HSCT) and blood draw, time since cGvHD diagnosis, and steroid dose. 

Key data: cGVHD was mild in 18%, moderate in 47%, and severe in 35% of patients. Involved organs included the skin (67%), mouth (60%), eye (49%), joints (34%), gastrointestinal tract (GI; 31%), lung (23%), and liver (17%). After adjustment for five clinical variables, 14 out of the 28 plasma proteins measured were associated with organ involvement, of which 13 were significantly associated with at least one organ manifestation, including IL-18, CXCL9, CXCL10, IL-6, IL-8, MCP1, BAFF, IL1RL1 (ST2), Reg3a, MMP3, DKK3, and CD163. All organs except the eye had at least one plasma protein association at p < 0.05. However, no combination of plasma proteins improved model fit after adjustment for patient- and transplant-related clinical variables.

Key learning: Although statistically significant correlations between plasma proteins and organ involvement were identified in patients with cGvHD, these were not considered clinically actionable. Future biomarker research should focus on proximal cellular and molecular determinants of cGvHD biology in blood and tissue.