Elafin Is a Biomarker of Graft Versus Host Disease of the Skin

There are no plasma biomarkers that are specific to any of the three target organs of acute graft versus host disease (GVHD): skin, GI tract and liver. We sought to identify a biomarker that is specific for GVHD of the skin in an initial discovery step using an intact proteomic analysis system. We compared plasma pooled from ten patients with GVHD only of the skin (sGVHD) to plasma pooled from ten patients with no GVHD to plasma pooled from ten patients with GVHD only of the GI tract. Of four candidate proteins that were both significantly elevated only in the plasma of sGVHD patients and that could be measured by ELISA, we selected elafin, an epidermal proteinase inhibitor that is induced by TNF-α and found in inflamed epidermis in diseases such as psoriasis. We therefore measured levels of elafin (expressed hereafter as mean ± SEM pg/ml) in individual samples of the discovery set, confirming that they were significantly higher in plasma from patients with sGVHD compared to patients presenting only with GI GVHD or without GVHD, respectively (13,312 ± 2456 vs. 3968 ± 537 vs. 3257 ± 332, p eventual maximum stage of GVHD skin, transplant-related mortality and overall survival. We divided the patients into 2 groups using a threshold level of elafin that provided 85% specificity (5500 pg/ml). The group with the high levels of elafin comprised 29% of the total patient population and developed more severe skin GVHD (maximum stage) than the group with low levels (p Table 1: Correlating low/high elafin with maximum skin stage Maximum skin stage