Decreased Plasma Level of Cytokeratin 20 (KRT20) Is Indicative of the Emergence and Severity of Acute GvHD Irrespective to the Type of Organ Involvement

Abstract

Accurate risk prediction of acute graft versus host disease (aGvHD) is currently an unmet clinical need. This study sought to analyze whether three plasma proteins expressed in a largely skin- and gut-restricted manner would be affected by the development of acute cutaneous and gastrointestinal aGvHD. The diagnostic sensitivity, specificity, and prognostic value of plasma cytokeratin-15 (KRT15) cytokeratin-20 (KRT20), and occludin (OCLN) were evaluated in a discovery and a validation cohort using ELISA in comparison with elafin (PI3) and regenerating family member 3 alpha (REG3A), two established markers of skin- and gut aGvHD. The discovery cohort (n = 39) revealed that at the time of diagnosis, plasma KRT20 showed a progressive decrease from unaffected individuals to patients with single-, and patients with multi-organ aGvHD. KRT20 was affected by cutaneous (p = 0.0263) and gastrointestinal aGvHD (p = 0.0242) independently and in an additive manner. Sensitivity and specificity of KRT20 for aGvHD involving both target organs (AUC = 0.852) were comparable to that of PI3 for skin-aGvHD (AUC = 0.708) or that of REG3A for gut-aGvHD (AUC = 0.855). Patient follow-up in the validation cohort (n = 67) corroborated these observations (p < 0.001), and linked low KRT20 to grade 2+ disease (p < 0.001), but failed to confirm low KRT20 as an independent risk factor. These data established a link between low plasma KRT20 levels and moderate to severe aGvHD involving multiple target organs.

Activated CD4 + T lymphocyte is a potential biomarker for acute graft-vs.-host disease after hematopoietic stem cell transplantation in children with transfusion-dependent β-thalassemia

“…HSCT is currently the only method that can be promoted to cure thalassemia. Despite significant advances in prophylaxis and therapy, acute graft vs. host disease (aGVHD) remains one of the most common and life-threatening complications of allogeneic HSCT (5), resulting in considerable morbidity and mortality (6). The cumulative incidence of grade II-IV aGVHD in children who have received allogeneic HSCT ranges from 28 to 56% (7)(8)(9).…”