True infliximab resistance in rheumatoid arthritis:: a role for lymphotoxin α?
True infliximab resistance in rheumatoid arthritis:: a role for lymphotoxin α?
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DOI：
10.1136/ard.2003.014878
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发表时间：
2004-10-01
影响因子：
27.4
通讯作者：
Emery, P
中科院分区：
文献类型：
--
作者：
Buch, MH;Conaghan, PG;Emery, P
背景：甲氨蝶呤联合抗肿瘤坏死因子α (TNFalpha)抗体英夫利昔单抗是治疗类风湿性关节炎（RA）非常有效的方法。然而，一部分患者对这种治疗没有反应。无效可能代表与TNFalpha无关的疾病或作用部位的药物不足。病例报告：描述了一名RA患者对反复高剂量英夫利昔单抗输注和发炎膝盖关节内英夫利昔单抗耐药。没有观察到有益的临床效果。注射前膝关节镜活检显示TNFalpha染色，但免疫组化也证实淋巴蛋白α （LTalpha或tnf β）的存在。随后用依那西普（阻断LTalpha和TNFalpha）治疗导致疾病的临床缓解。结论：本病例提示，当TNF α不是主要的炎症细胞因子时，可能发生对TNF阻断的抵抗，提示LTalpha可能在RA中起致病作用。
Background: The combination of methotrexate and the antitumour necrosis factor alpha (TNFalpha) antibody infliximab is a very effective treatment for rheumatoid arthritis (RA). However, a proportion of patients are not responsive to this treatment. Inefficacy may represent a TNFalpha independent disease or insufficient drug at the site of action.Case report: A patient with RA resistant to repeated high dose infliximab infusions and intra-articular infliximab into an inflamed knee is described. No beneficial clinical effect was observed. Pre-injection arthroscopic biopsy of the study knee demonstrated TNFalpha staining but also confirmed the presence of lymphotoxin alpha (LTalpha or TNFbeta) on immunohistochemistry. Subsequent treatment with etanercept ( which blocks LTalpha as well as TNFalpha) resulted in clinical remission of disease.Conclusion: This case suggests that resistance to TNF blockade may occur when TNFalpha is not the dominant inflammatory cytokine and suggests that LTalpha may have a pathogenic role in RA.