To explore the correlation of IL-6, IL-8, soluble tumor necrosis factor receptor 1 (sTNFR1), regenerating islet-derived protein 3-alpha (Reg3α), soluble suppression of tumorigenesis 2 (sST2) and elafin with acute graft versus host disease (aGVHD) following allogeneic hematopoietic stem cell transplantation (allo-HSCT).

A retrospective analysis was conducted on the clinical data of 106 patients who underwent allo-HSCT in the Department of Hematology at the 940th Hospital of the Joint Logistics Support Force of PLA between January 2019 and January 2023. Forty-nine patients who developed aGVHD were assigned to the aGVHD group, while 57 patients without aGVHD were included in the non-aGVHD group. Peripheral blood samples were collected from all patients at post-transplantation days + 28, + 56, and + 90 for cytokine quantification. Intergroup comparisons of normally distributed continuous variables were performed using the independent samples t-test. The Mann-Whitney U test was employed for non-normally distributed continuous variables. Categorical variables were compared using the chi-square test. A P-value < 0.05 was considered statistically significant.

At days + 28, sST2 level was significantly lower in the non-aGVHD group [52.2 (34.9-93.0) pg/mL] compared to the aGVHD group [98.2 (58.3-186.7) pg/mL], Z=-3.268, P < 0.05. At days + 56, the non-aGVHD group exhibited significantly reduced level of sTNFR1 [1 971.2 (1 656.8-2 537.0) pg/mL], sST2 [76.4 (40.0-134.4) pg/mL], and Reg3α [38.8 (23.8-92.6) pg/mL] relative to the aGVHD group [sTNFR1 2 791.2 (1 698.4-3 468.2) pg/mL, sST2 191.0 (113.5-620.2) pg/mL, Reg3α 77.0 (41.5-162.0) pg/mL], Z=-2.926, -4.420 and -3.393, all P < 0.05. At days + 90, the sST2 level was lower in the non-aGVHD group [78.6 (51.0-107.1) pg/mL] than the aGVHD group [146.9 (81.0-327.8) pg/mL], Z=-3.578, P<0.05. Patients with grade Ⅱ-Ⅳ aGVHD demonstrated significantly elevated sTNFR1 level at days + 56 [3 245.4 (2 804.6-3 557.6) pg/mL] and days + 90 [2 891.2 (2 024.6-4 534.0) pg/mL], as well as higher Reg3α level at days + 56 [162.0 (65.4-310.3) pg/mL] and days + 90 [92.5 (58.1-157.7) pg/mL] compared to those with grade Ⅰ aGVHD [sTNFR1 2 009.7 (1 599.5-3 259.1) pg/mL at days + 56, 1 870.9 (1 620.2-2 334.4) pg/mL at days + 90, Reg3α 53.7 (33.2-79.7) pg/mL at days + 56, 43.9 (39.2-64.7) pg/mL at days + 90], Z=-2.639, -2.242, -3.026 and -2.743, all P<0.05. Additionally, elafin level was significantly higher in the grade Ⅱ-Ⅳ aGVHD group [14.0 (10.3-24.7) pg/mL] versus the grade Ⅰ group [8.4 (7.5-14.3) pg/mL] at days + 90 (Z=-2.162, P<0.05). Patients in the gastrointestinal aGVHD group exhibited significantly increased Reg3α level at days + 28 [94.7 (27.9-307.8) pg/mL], days + 56 [306.4 (162.1-524.4) pg/mL], and days + 90 [124.5 (70.1-312.8) pg/mL] compared to those in the non-gastrointestinal aGVHD group [33.5 (19.6-57.3), 53.8 (33.8-81.7) and 43.9 (37.6-66.7) pg/mL, respectively], Z= -2.352, -3.857 and -2.800, all P<0.05. Similarly, sTNFR1 level significantly elevated in the gastrointestinal aGVHD group at days + 56 [3 250.5 (2 980.8-4 413.2) pg/mL] and days + 90 [4 534.0 (2 419.4-6 171.2) pg/mL] relative to the non-gastrointestinal aGVHD group [2 189.4 (1 609.7-3 297.1) pg/mL and 1 885.2 (1 715.0-2 530.0) pg/mL, respectively], Z=-2.842 and -2.100, all P<0.05.

The serum biomarkers (sST2, sTNFR1, Reg3α and elafin) are associated with the occurrence and severity of aGVHD in patients treated with allo-HSCT, which may be valuable for clinical diagnosis and intervention.