Intestinal fibrosis is associated with lack of response to Infliximab therapy in Crohn's disease.
Intestinal fibrosis is associated with lack of response to Infliximab therapy in Crohn's disease.
复制标题
肠纤维化与克罗恩病中英夫利昔单抗治疗的反应有关。
DOI：
10.1371/journal.pone.0190999
复制
发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
D'Haens GR
中科院分区：
文献类型：
--
作者：
de Bruyn JR;Becker MA;Steenkamer J;Wildenberg ME;Meijer SL;Buskens CJ;Bemelman WA;Löwenberg M;Ponsioen CY;van den Brink GR;D'Haens GR
明显的纤维狭窄性疾病是克罗恩病抗TNF治疗的相对禁忌症。我们假设亚临床纤维化也可能导致在症状性狭窄发生前对抗TNF治疗反应不完全。在先前的试验中，回盲部克罗恩病患者被随机分为立即回盲部切除术组或英夫利昔单抗药物治疗组。在对英夫利西单抗反应不足的情况下，后者接受了二次回盲部切除术。我们比较了接受立即切除术（英夫利西单抗初治，n = 20）和英夫利西单抗治疗失败（n = 20）患者的标本。通过CRP水平（中位数14 vs 9 mg/L）和组织学（Geboes-D 'Haens评分，中位数10 vs 11分）评估时，英夫利西单抗初治患者和英夫利西单抗治疗失败患者的炎症严重程度相似。免疫组化显示，与未接受过英夫利西单抗治疗的患者相比，既往接受过英夫利西单抗治疗的患者中III型胶原和纤连蛋白沉积增加。在mRNA水平上，前胶原肽酶在因夫利西单抗治疗失败的克罗恩病患者中显示出显著更多的粘膜mRNA表达。英夫利西单抗应答者在成功英夫利西单抗治疗4周后未显示该标志物增加。英夫利西单抗治疗失败与克罗恩病的亚临床纤维化有关。
Overt fibrostenotic disease is a relative contraindication for anti-TNF therapy in Crohn’s disease. We hypothesized that subclinical fibrosis may also contribute to an incomplete response to anti-TNF therapy before the onset of symptomatic stenosis. In a previous trial, patients with ileocecal Crohn’s disease were randomized to either immediate ileocecal resection or medical treatment with Infliximab. In case of insufficient response to Infliximab, the latter underwent secondary ileocecal resection. We compared specimens from those patients undergoing immediate resection (Infliximab naïve, n = 20) to those who failed Infliximab therapy (n = 20). Infliximab naïve and Infliximab failure patients had similar severity of inflammation when assessed by CRP levels (median 14 vs 9 mg/L) and histology (Geboes-D’Haens-score, median 10 vs 11 points). On immunohistochemistry, collagen-III and fibronectin depositions were increased in patients previously exposed to Infliximab compared to patients naïve to Infliximab. On mRNA level, procollagen peptidase showed significantly more mucosal mRNA expression in Crohn’s disease patients who failed Infliximab. Infliximab responders showed no increase of this marker after 4 weeks of successful Infliximab treatment. Failure to Infliximab therapy is associated with subclinical fibrosis in Crohn’s disease.
登录
查看更多内容
DOI：
10.1073/pnas.84.20.7179
发表时间：
1987-10-01
影响因子：
11.1
作者：
GUTMAN, A;KORNBLIHTT, AR
通讯作者：
KORNBLIHTT, AR
影响因子：
29.4
作者：
Atreya, Raja;Zimmer, Michael;Neurath, Markus F.
通讯作者：
Neurath, Markus F.
影响因子：
4
作者：
PELTONEN, L;HALILA, R;RYHANEN, L
通讯作者：
RYHANEN, L
纤连蛋白结构域ED-A通过转化生长因子-Beta1，对于肌纤维细胞表型诱导至关重要。
影响因子：
7.8
作者：
Serini, G;Bochaton-Piallat, M L;Ropraz, P;Geinoz, A;Borsi, L;Zardi, L;Gabbiani, G
通讯作者：
Gabbiani, G
影响因子：
29.4
作者：
FARMER, RG;WHELAN, G;FAZIO, VW
通讯作者：
FAZIO, VW