Epidermal Elafin Expression Is an Indicator of Poor Prognosis in Cutaneous Graft-versus-Host Disease

Abstract

Graft-versus-host disease (GVHD) remains a common and potentially life-threatening complication of allogeneic hematopoietic stem cell transplantation. In the skin, GVHD can present in an acute (aGVHD), chronic lichenoid (clGVHD), or chronic sclerotic form (csGVHD). Measuring peripheral blood levels of the keratinocyte-derived protease inhibitor elafin has recently emerged as a promising tool for the diagnosis of cutaneous aGVHD. We evaluated whether the analysis of elafin expression in skin would allow distinguishing aGVHD from drug hypersensitivity rashes (DHR) and whether cutaneous elafin expression would correlate with disease severity or altered prognosis of aGVHD and clGVHD/csGVHD. Skin biopsies from aGVHD (n=22), clGVHD (n=15), csGVHD (n=7), and DHR (n=10) patients were collected and epidermal elafin expression and its association with diverse clinical/histological parameters were analyzed. Acute GVHD and DHR displayed varying degrees of elafin expression. No elafin was detectable in csGVHD, whereas the molecule was increased in clGVHD as compared with aGVHD. Elafin-high aGVHD/clGVHD lesions presented with epidermal thickening and were associated with poor prognosis-i.e., decreased overall survival in aGVHD and corticosteroid resistance in clGVHD. Although cutaneous elafin does not seem to discriminate aGVHD from DHR lesions, our study strongly suggests an association between cutaneous elafin expression and poor prognosis for patients with cutaneous GVHD.

Utility of tissue elafin as an immunohistochemical marker for diagnosis of acute skin graft-versus-host disease: a pilot study

“…There have been only a few studies on epidermal elafin expression in skin GvHD . Bruggen et al . found diverse elafin expression patterns in skin biopsies of acute GvHD and chronic lichenoid GvHD.…”

“…Recently, elafin was identified as an important plasma biomarker for skin GvHD, and for predicting transplant survival and response to treatment . Elafin has also been found to be overexpressed in skin biopsies in acute and chronic skin GvHD . Immunohistochemistry (IHC) for elafin expression in skin GvHD biopsies has been studied by very few investigators .…”

“…Elafin has also been found to be overexpressed in skin biopsies in acute and chronic skin GvHD . Immunohistochemistry (IHC) for elafin expression in skin GvHD biopsies has been studied by very few investigators . While these studies found that elafin is overexpressed in these biopsies from skin GvHD, there were contradictory findings regarding the ability of tissue elafin to distinguish between GvHD and its close mimic, maculopapular drug rash …”

Biomarkers for posttransplantation outcomes

“…c Elafin was discovered using next-generation proteomics and samples from skin aGVHD and supports the specific diagnosis of aGVHD in plasma and skin biopsies. 67,68 However, the ELISA for elafin lacked reproducibility, and elafin as a prognostic biomarker has been difficult to reproduce in large cohorts, although it remains a good marker for individual patients at time of diagnosis of skin GVHD and for monitoring of response (Stephanie J. Lee, International applied biology in chronic GVHD working group meeting, oral communication, 24 March 2017). c Regenerating islet-derived 3-a (Reg3a) and T-cell immunoglobulin mucin-3 (TIM3) were discovered using next-generation proteomics and samples from lower GI aGVHD and validated in several cohorts alone or combined with other markers.…”

Biomarkers for Allogeneic HCT Outcomes

“…Skin specific Elafin. Elafin was also discovered using nextgeneration proteomics and validated as both a diagnostic and prognostic biomarker for skin GVHD, which is associated with GVHD severity and NRM (67,68).…”