Regenerating islet-derived protein 3-α is a prognostic biomarker for gastrointestinal chronic graft-versus-host disease.
Regenerating islet-derived protein 3-α is a prognostic biomarker for gastrointestinal chronic graft-versus-host disease.
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DOI：
10.1182/bloodadvances.2021005420
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发表时间：
2022-05-24
期刊：
影响因子：
7.5
通讯作者：
Paczesny, Sophie
中科院分区：
文献类型：
--
作者：
DePriest, Brittany Paige;Li, Hong;Bidgoli, Alan;Onstad, Lynn;Couriel, Daniel;Lee, Stephanie J.;Paczesny, Sophie
在2个独立队列中，GI-cGVHD患者的血浆Reg3α水平显著高于非GI-cGVHD患者。REG3型α是判断GI-cGVHD患者发生NRM可能性的预后生物标志物。用于确定疾病进展可能性的预后生物标志物尚未被确定为慢性移植物抗宿主病(CGVHD)，这是异基因造血细胞移植幸存者晚期无复发死亡(NRM)的主要原因。胃肠道cGVHD(GI-cGVHD)的分类尤其具有挑战性。在这里，我们分析了3个蛋白质组学标记(再生胰岛衍生蛋白3-α[α]，C-X-C基序配体9[CXCL9]和刺激-2[ST2])在2个独立的队列中，总计289名患者。GI-cGVHD患者的血浆Reg3α浓度显著高于非GI-cGVHD患者(P=0.0012)，而CXCL9和ST2的血浆浓度无明显变化。与低Reg3α(≥相比，Reg3α高达72 ng/mL的患者有更高的NRM值(23%比11%；P=0.015)。由于Reg3α已被确定为急性移植物抗宿主病的下消化道标志物，我们将Reg3α与低急性GI-cGVHD和经典的纤维化样食道表现相关联，发现Reg3α在不同亚型之间没有差异。上消化道亚型与下消化道亚型间差异无统计学意义。Reg3α(≥极高的患者有较高的GI评分，但下消化道评分并不高。在多变量COX回归模型中，Reg3α升高的患者无复发死亡的可能性是后者的1.9倍。我们的研究结果证明了Reg3α作为GI-cGVHD预后标志物的实用性。这些数据为前瞻性生物标记物验证研究提供了依据。
Plasma levels of Reg3α were significantly increased in patients with GI-cGVHD compared with those without GI-cGVHD in 2 independent cohorts. Reg3α is a prognostic biomarker that identifies the likelihood of NRM in patients with GI-cGVHD. Prognostic biomarkers used to identify likelihood of disease progression have not been identified for chronic graft-versus-host disease (cGVHD), the leading cause of late nonrelapse mortality (NRM) in survivors of allogeneic hematopoietic cell transplantation. Gastrointestinal cGVHD (GI-cGVHD) has been particularly challenging to classify. Here, we analyzed 3 proteomics markers (Regenerating islet-derived protein 3-α [Reg3α], C-X-C motif ligand 9 [CXCL9], and Stimulation-2 [ST2]) in 2 independent cohorts of patients with cGVHD totaling 289 patients. Plasma concentrations of Reg3α were significantly increased in patients with GI-cGVHD (P = .0012) compared with those without (P = .01), but plasma concentrations of CXCL9 and ST2 were not. Patients with high Reg3α (≥72 ng/mL) vs low Reg3α had higher NRM (23% vs 11%; P = .015). Because Reg3α has been identified as a lower GI tract marker in acute GVHD, we correlated Reg3α with lower acute-like GI-cGVHD vs classical fibrotic-like esophageal manifestations and found that Reg3α did not differ between the subtypes. No difference was observed between upper GI tract and lower GI tract subtypes. Patients with extremely high Reg3α (≥180 ng/mL) had higher GI scores but not higher scores for the lower GI tract. In a multivariable Cox regression model, patients with high Reg3α were 1.9 times more likely to die without relapse. Our findings demonstrate the utility of Reg3α as a prognostic marker for GI-cGVHD. These data warrant prospective biomarker validation studies.
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影响因子：
3.2
作者：
Pidala J;Kitko C;Lee SJ;Carpenter P;Cuvelier GDE;Holtan S;Flowers ME;Cutler C;Jagasia M;Gooley T;Palmer J;Randolph T;Levine JE;Ayuk F;Dignan F;Schoemans H;Tkaczyk E;Farhadfar N;Lawitschka A;Schultz KR;Martin PJ;Sarantopoulos S;Inamoto Y;Socie G;Wolff D;Blazar B;Greinix H;Paczesny S;Pavletic S;Hill G
通讯作者：
Hill G
抗菌蛋白REG3A调节皮肤损伤后角质形成细胞增殖和分化。
影响因子：
32.4
作者：
Lai Y;Li D;Li C;Muehleisen B;Radek KA;Park HJ;Jiang Z;Li Z;Lei H;Quan Y;Zhang T;Wu Y;Kotol P;Morizane S;Hata TR;Iwatsuki K;Tang C;Gallo RL
通讯作者：
Gallo RL
影响因子：
3.2
作者：
Williams KM;Inamoto Y;Im A;Hamilton B;Koreth J;Arora M;Pusic I;Mays JW;Carpenter PA;Luznik L;Reddy P;Ritz J;Greinix H;Paczesny S;Blazar BR;Pidala J;Cutler C;Wolff D;Schultz KR;Pavletic SZ;Lee SJ;Martin PJ;Socie G;Sarantopoulos S
通讯作者：
Sarantopoulos S
TLR3-SLUG-VDR 轴诱导的 IL-36γ 通过 REG3A 促进伤口愈合
影响因子：
6.5
作者：
Jiang, Ziwei;Liu, Yuanqi;Lai, Yuping
通讯作者：
Lai, Yuping
DOI：
10.1016/j.bbmt.2014.12.001
发表时间：
2015-03
期刊：
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
影响因子：
--
作者：
Jagasia MH;Greinix HT;Arora M;Williams KM;Wolff D;Cowen EW;Palmer J;Weisdorf D;Treister NS;Cheng GS;Kerr H;Stratton P;Duarte RF;McDonald GB;Inamoto Y;Vigorito A;Arai S;Datiles MB;Jacobsohn D;Heller T;Kitko CL;Mitchell SA;Martin PJ;Shulman H;Wu RS;Cutler CS;Vogelsang GB;Lee SJ;Pavletic SZ;Flowers ME
通讯作者：
Flowers ME