ArticleModern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc2019
Amphiregulin in intestinal acute graft-versus-host disease: a possible diagnostic and prognostic aid.
Article in Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 15 citations in OpenAlex.
- Prediction and Prognostication of Acute Graft-Versus-Host Disease by MAGIC Biomarkers.American journal of hematology · 2025Review
- Biochemical markers and emerging therapies for intestinal manifestation of graft-versus-host disease.Frontiers in immunology · 2025Review
- Amphiregulin, ST2, and REG3α biomarker risk algorithms as predictors of nonrelapse mortality in patients with acute GVHD.Blood advances · 2024Article
- Amphiregulin as a biomarker for monitoring lifethreatening acute graft-Haematologica · 2024Article
- Biomarkers for early complications post hematopoietic cell transplantation: Insights and challenges.Frontiers in immunology · 2023Review
- High cutaneous amphiregulin expression predicts fatal acute graft-versus-host disease.Journal of cutaneous pathology · 2022Article
- Increased amphiregulin expression by CD4Clinical & translational immunology · 2022Article
- Obesity induces gut microbiota alterations and augments acute graft-versus-host disease after allogeneic stem cell transplantation.Science translational medicine · 2020Article
- Blood and Salivary Amphiregulin Levels as Biomarkers for Asthma.Frontiers in medicine · 2020Article
- Stress responses, M2 macrophages, and a distinct microbial signature in fatal intestinal acute graft-versus-host disease.JCI insight · 2019Article
- Biomarkers in acute graft-Therapeutic advances in hematology · 2019Review
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Authors and funding
16 authors at 2 institutions in 1 country.
Funding
Abstract
Amphiregulin, a weak epidermal growth factor receptor agonist, is elevated, while epidermal growth factor, a strong epidermal growth factor receptor agonist, is low in the blood of patients with severe acute graft-versus-host disease. However, the tissue expression and function of these epidermal growth factor receptor ligands in acute graft-versus-host disease target organs is unknown. We compared by immunohistochemistry expression of amphiregulin and epidermal growth factor in archived, formalin-fixed, paraffin-embedded intestinal tissues of 48 patients with biopsy-proven gastrointestinal acute graft-versus-host disease to 3 groups: (1) 10 non-hematopoietic cell transplant normal controls, (2) 11 patients with newly diagnosed ulcerative colitis (ulcerative colitis), (3) 8 patients with a clinical diagnosis of acute graft-versus-host disease despite pathologically non-diagnostic biopsies, (4) and 10 cases of cytomegalovirus colitis. We used a semi-quantitative score of 0 (absent) through 3 (strong) to describe the intensity of immunohistochemical staining. We correlated serum and tissue amphiregulin and epidermal growth factor in patients with acute graft-versus-host disease. Gastrointestinal amphiregulin was significantly lower in acute graft-versus-host disease biopsies (median score 1), ulcerative colitis (median score 1.5), and cytomegalovirus colitis (median score 1) than in normal colon (median score 2, p = 0.004, p = 0.03, p = 0.009 respectively). Amphiregulin expression in was low in 74% of acute graft-versus-host disease cases with or without significant apoptosis. Patients with acute graft-versus-host disease exhibiting the pattern of high gastrointestinal amphiregulin but low serum amphiregulin (n = 14) had the best 1-year survival at 71%, but patients with high serum amphiregulin had poorer survival (<30%) regardless of gastrointestinal amphiregulin expression. Overall, our results lead to the hypothesis that amphiregulin is released into the circulation from damaged intestinal epithelium and stroma, although contributions from other cellular sources are likely. Low gastrointestinal amphiregulin expression by immunohistochemistry may be further studied for its utility in the pathologic acute graft-versus-host disease diagnosis without classic apoptotic changes.
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