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Updated: Oct 2, 2025

High Throughput Sequential ELISA for Validation of Biomarkers of Acute Graft-Versus-Host Disease
Published on: October 31, 2012
High cutaneous amphiregulin expression predicts fatal acute graft-versus-host disease
Brittney Schultz1, Daniel D Miller1, Todd DeFor2,3
1Department of Dermatology, University of Minnesota, Minneapolis, Minnesota, USA.
Background:
Amphiregulin (AREG) is increased in circulation in acute graft-versus-host disease (aGVHD) and is associated with poor steroid response and lower survival. The expression of AREG in aGVHD target organs and its association with clinical outcomes are unknown.
Methods:
We performed AREG immunohistochemical staining on skin specimens from 67 patients with aGVHD between the years 2010 and 2015. Two blinded reviewers assessed AREG expression and scored specimens with a semiquantitative scale ranging from 0 (absent) to 4 (most intense).
Results:
Median AREG score of aGVHD cases was 3. Sixteen of 67 (23.9%) aGVHD cases had an AREG >3. High skin AREG expression (>3 vs. ≤3) was associated with increased overall clinical grade of aGVHD (52.9% vs. 33.4% clinical grade III-IV, p = 0.02), reduced 3-year overall survival (OS; 13% vs. 61%, p < 0.01), and increased 3-year non-relapse mortality (NRM; 56% vs. 20%, p = 0.05).
Conclusion:
High skin AREG immunohistochemical expression is associated with high clinical grade aGVHD, poor OS, and increased NRM.

