Monitoring of TNFR1, IL-2Rα, HGF, CCL8, IL-8 and IL-12p70 following HSCT and their role as GVHD biomarkers in paediatric patients

Abstract

No predictive factors are currently available to establish patient-specific GVHD risk. A panel of six serum cytokines (TNF receptor 1, IL-2 receptor alfa (IL-2Ra), hepatocyte growth factor (HGF), monocyte chemo-attractant protein-2, IL-8, IL-12p70) were monitored at established time points (days À 1, þ 1, þ 7, þ 14, þ 21, þ 28 and þ 60) in 170 paediatric hematopoietic SCT (HSCT) recipients. We found that higher concentrations of IL-2Ra on days þ 14 and þ 21 together with HGF on days þ 14 and þ 21 were significantly associated at a higher probability of both grade II-IV GVHD (on day þ 14 it was: 60% vs 28%, P ¼ 0.007) and grade III-IV (on day þ 14 it was: 40% vs 15%, P ¼ 0.001). The higher IL-8 serum concentration on day þ 28 was associated with a lower probability of chronic GVHD being 4% vs 29% (P ¼ 0.01) for patients with higher vs lower IL-8 serum concentration. These findings were confirmed when the analysis was restricted to the the matched unrelated donor group. In conclusion, even if the serum cytokine levels were related to several variables associated with HSCT, we identified two cytokines as predictors of GVHD II-IV and III-IV, translating into a higher TRM risk (17% vs 3%, P ¼ 0.004).

Immune Reconstitution after Allogeneic Hematopoietic Cell Transplantation in Children

“…However, high IL-7 levels were also related to increased mortality and aGVHD [91]. Other potential biomarkers for aGVHD, which can be found at least several days to even weeks before its onset, are high levels of IL-6, granulocyte macrophage colonyestimulating factor, hepatocyte growth factor, and IL-2Ra, the latter 2 being related to visceral or skin aGVHD, respectively [93,95,96]. A high suppressor of tumorigenicity 2 level at day 28 is a strong indicator of grades II to IV or III and IV aGVHD and TRM [98].…”

“…A high suppressor of tumorigenicity 2 level at day 28 is a strong indicator of grades II to IV or III and IV aGVHD and TRM [98]. High levels of IL-8 are associated with lower probability of cGVHD and low levels of IL-17A predict increased probability of cGVHD [95,97]. Moreover, biomarkers for viral reactivation are again IL-6, which peaks 1 to 3 weeks before onset, but also TNF-a, which is an indicator for an ongoing viral reactivation [92].…”

Biomarkers in Ocular Chronic Graft Versus Host Disease: Tear Cytokine- and Chemokine-Based Predictive Model

“…9 Some research groups have reported the possibility that levels of certain cytokines in serum can serve as specific biomarkers of GVHD and thus have the potential to act as accurate diagnostic and prognostic tools. 10,11 Regarding ocular cGVHD, our group has already shown that inflammatory gene expression in conjunctival epithelial cells may act as biomarkers for this disease. 12 However, identifying tear biomarkers in ocular cGVHD is even more desirable, because tears can easily be obtained in a noninvasive manner, and their close anatomical relationship to the disease site makes them highly specific for ocular disease.…”

Circulating Levels of Adipokines Predict the Occurrence of Acute Graft-versus-host Disease

“…Kuroiwa and colleagues were able to maintain continuous levels of the polyfunctional cytokine by repeatedly transfecting human HGF cDNA into skeletal muscle, and they observed that two of the characteristic findings in GVHD, crypt cell apoptosis and infiltration of lymphocytes into the portal triad, were absent in the treated animals ( 21 ). This study identified the protective effect of HGF although HGF levels were significantly associated with a higher probability of GVHD ( 22 , 23 ).…”