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. 2010 Jan 6;2(13):13ra2.
doi: 10.1126/scitranslmed.3000406.

Elafin is a biomarker of graft-versus-host disease of the skin

Sophie Paczesny  1 , Thomas M Braun, John E Levine, Jason Hogan, Jeffrey Crawford, Bryan Coffing, Stephen Olsen, Sung W Choi, Hong Wang, Vitor Faca, Sharon Pitteri, Qing Zhang, Alice Chin, Carrie Kitko, Shin Mineishi, Gregory Yanik, Edward Peres, David Hanauer, Ying Wang, Pavan Reddy, Samir Hanash, James L M Ferrara
Affiliations

Elafin is a biomarker of graft-versus-host disease of the skin

Sophie Paczesny et al. Sci Transl Med. .

Abstract

Graft-versus-host disease (GVHD), the major complication of allogeneic bone marrow transplantation, affects the skin, liver, and gastrointestinal tract. There are no plasma biomarkers specific for any acute GVHD target organ VSports手机版. We used a large-scale quantitative proteomic discovery procedure to identify biomarker candidates of skin GVHD and validated the lead candidate, elafin, with enzyme-linked immunosorbent assay in samples from 492 patients. Elafin was overexpressed in GVHD skin biopsies. Plasma concentrations of elafin were significantly higher at the onset of skin GVHD, correlated with the eventual maximum grade of GVHD, and were associated with a greater risk of death relative to other known risk factors (hazard ratio, 1. 78). We conclude that elafin has significant diagnostic and prognostic value as a biomarker of skin GVHD. .

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Conflict of interest statement

Competing interest’s statement

The authors declare that they have no competing financial interests.

Figures

Figure 1
Figure 1. Proteomic workflow for elafin discovery
A) Overview of the proteomic workflow for Intact Protein Analysis System (IPAS). B) Tandem mass spectrum of the identified peptide, elafin. bn or yn denotes the fragment ion generated by cleavage of the peptide bond after the nth amino acid containing either the peptide N-terminus (b series) or the C-terminus (y series), respectively. The identified b- and y-ions and all fragment ion mass/charge (m/z) values are indicated in the table. C* denotes cysteine residues modified by acrylamide containing 3 13C atoms. The identified peptide sequence location is written in bold in the protein sequence.
Figure 2
Figure 2. Skin biopsies from BMT patients
Skin biopsies from BMT patients with rashes immunohistochemically stained for elafin. A) Biopsies histologically confirmed as drug hypersensitivity showed staining only in the granular cell layer (arrow). B) Biopsies histologically confirmed as GVHD showed a strong positive staining of at least 50% of the layers in epidermis. Scale bar = 50 μm, the dashed line represents the epidermal/dermal junction. C) Plasma elafin levels in biopsied patients (N=10 per group).
Figure 3
Figure 3. Elafin plasma levels in BMT patients of the validation set
A) Plasma elafin levels in BMT patient samples measured by ELISA. B) Plasma elafin levels stratified to the stage of skin GVHD at presentation. C) Elafin levels in patients with rashes covering equivalent percentages of body surface area (Area).
Figure 4
Figure 4. ROC curves comparing skin GVHD and non-GVHD rashes
ROC curves for Elafin, TNFR1, IL-2Rα, HGF, IL-8 and the composite curve of all five biomarkers (AUC = 0.77, 0.73, 0.65, 0.62, 0.54 and 0.84, respectively) comparing patients with skin-GVHD (N=58) vs. non-GVHD rash (N=53).
Figure 5
Figure 5. Nonrelapse mortality (NRM), relapse, and overall survival (OS) according to plasma elafin levels in BMT patients with rashes
Patients with GVHD of the skin (N=159) were divided into two equal groups according to elafin level: low ( < 6000 pg/ml, N=79) and high (≥ 6000 pg/ml, N=80). The cumulative incidence of NRM (A), relapse mortality (B) and overall survival (C) were determined by Kaplan Meier and plotted for each group. The same analysis was performed for all BMT patients with rashes (N = 212, D–F).
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References

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