OBJECTIVETo observe the relationship between variation of IL-2, IL-4, IL-18 and IP10 mRNA expressions in peripheral blood and the occurrence of acute graft-versus-host disease (aGVHD), and investigate whether some cytokines combined expression profiles could improve the diagnostic accuracy of aGVHD.

METHODSA total of 58 patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) were enrolled for the study. Peripheral blood samples were collected at different time points after transplantation. The mRNA expression levels of 4 kinds of cytokines (IL-2, IL-4, IL-18, IP10) were measured by real-time quantitative PCR (RQ-PCR). The relationship between mRNA expression level and the occurrence of aGVHD was analyzed with clinical features.

RESULTSThe expression levels of IL-2 and IL-18 at the onset of aGVHD were much higher than those after engraftment, being 2.69-fold and 3.12-fold increase, respectively (P = 0.000 & P = 0.000). The expressions of IL-2 and IL-18 mRNAs were slightly increased in patients with infection, but not statistically significant (P = 0.208 & P = 0.123). There was a slight but not statistically significant decrease of IL-4 and IP10 mRNA expressions at the onset of aGVHD (P = 0.230 & P = 0.325). Either IL-2 or IL-18 expression level could diagnose aGVHD as an independent factor (P = 0.000 & P = 0.000). The multivariate logistic regression analysis showed that the main factors related to aGVHD were IL-2, IL-18 and IL-4 (β = 1.13, P = 0.068 & β = 1.339, P = 0.047 & β = -0.600, P = 0.008 respectively). A composite panel of these three cytokines produced a better model for the diagnosis of aGVHD (AUC: 0.862, 95%CI: 0.768 - 0.957, P = 0.000), and the sensitivity and specificity were 75.0% & 83.3% respectively.

CONCLUSIONThe diagnosis of aGVHD can be optimized with a composite cytokines panel.