Amphiregulin in intestinal acute graft-versus-host disease: a possible diagnostic and prognostic aid.
Amphiregulin in intestinal acute graft-versus-host disease: a possible diagnostic and prognostic aid.
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DOI：
10.1038/s41379-018-0170-z
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发表时间：
2019-04
期刊：
影响因子：
--
通讯作者：
Holtan SG
中科院分区：
文献类型：
--
作者：
Amin K;Yaqoob U;Schultz B;Vaughn BP;Khoruts A;Howard JR;DeFor TE;Forster C;Meyer C;Gandhi I;Weisdorf DJ;Rashidi A;MacMillan ML;Blazar BR;Panoskaltsis-Mortari A;Holtan SG
在严重急性移植物抗宿主病患者的血液中，双调蛋白（一种弱表皮生长因子受体激动剂）的水平升高，而表皮生长因子（一种强表皮生长因子受体激动剂）的水平较低。然而，这些表皮生长因子受体配体在急性移植物抗宿主病靶器官中的组织表达和功能尚不清楚。我们通过免疫组织化学方法将 48 例活检证实胃肠道急性移植物抗宿主病患者存档的福尔马林固定石蜡包埋肠组织中双调蛋白和表皮生长因子的表达与 3 组进行比较：（1）10 例非造血细胞移植正常对照，（2）11 例新诊断溃疡性结肠炎（溃疡性结肠炎）患者，（3）8 例临床诊断为急性移植物抗宿主病的患者。移植物抗宿主病，尽管病理学上无法诊断活检，(4) 和 10 例巨细胞病毒结肠炎。我们使用 0（不存在）到 3（强）的半定量评分来描述免疫组织化学染色的强度。我们将急性移植物抗宿主病患者的血清和组织双调蛋白与表皮生长因子相关联。急性移植物抗宿主病活检（中位评分 1）、溃疡性结肠炎（中位评分 1.5）和巨细胞病毒结肠炎（中位评分 1）中的胃肠道双调蛋白显着低于正常结肠（中位评分 2，分别为 p = 0.004、p = 0.03、p = 0.009）。在有或没有明显细胞凋亡的急性移植物抗宿主病病例中，双调蛋白表达较低，为 74%。表现出高胃肠道双调蛋白但低血清双调蛋白模式的急性移植物抗宿主病患者 (n = 14) 的 1 年生存率最高，为 71%，但无论胃肠道双调蛋白表达如何，血清双调蛋白高的患者的生存率较差 (<30%)。总体而言，我们的结果得出这样的假设：双调蛋白从受损的肠上皮和基质释放到循环中，尽管其他细胞来源的贡献也可能存在。通过免疫组织化学检测胃肠道双调蛋白低表达可进一步研究其在病理性急性移植物抗宿主病诊断中的实用性，而无需典型的细胞凋亡变化。
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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DOI：
10.1083/jcb.118.3.741
发表时间：
1992-08
期刊：
The Journal of cell biology
影响因子：
--
作者：
Johnson GR;Saeki T;Gordon AW;Shoyab M;Salomon DS;Stromberg K
通讯作者：
Stromberg K
影响因子：
--
作者：
Wang B;Yong H;Zhu H;Ni D;Tang S;Zhang S;Wang W;Zhou Y;Zhao W;Ding G;Zhu J;Li X;Feng Z
通讯作者：
Feng Z
影响因子：
20.3
作者：
Holtan, Shernan G.;Khera, Nandita;Pidala, Joseph
通讯作者：
Pidala, Joseph
影响因子：
6.7
作者：
Firth, James D.;Ekuni, Daisuke;Putnins, Edward E.
通讯作者：
Putnins, Edward E.
影响因子：
3.7
作者：
KAPLAN, EL;MEIER, P
通讯作者：
MEIER, P