类风湿关节炎中真正的英夫利昔单抗耐药：淋巴毒素α起作用吗？
True infliximab resistance in rheumatoid arthritis: a role for lymphotoxin alpha?
作者信息
Buch M H, Conaghan P G, Quinn M A, Bingham S J, Veale D, Emery P
机构信息
Academic Unit of Musculoskeletal Disease, 1st Floor, Leeds General Infirmary, Great George Street, Leeds LS1 3EX, UK.
出版信息
Ann Rheum Dis. 2004 Oct;63(10):1344-6. doi: 10.1136/ard.2003.014878. Epub 2004 Mar 19.
BACKGROUND
The combination of methotrexate and the anti-tumour 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.
背景
甲氨蝶呤与抗肿瘤坏死因子α（TNFα）抗体英夫利昔单抗联合使用是类风湿关节炎（RA）的一种非常有效的治疗方法。然而，一部分患者对这种治疗没有反应。治疗无效可能代表TNFα非依赖性疾病或作用部位药物不足。
病例报告
描述了一名对重复高剂量英夫利昔单抗静脉输注和向发炎膝关节内注射英夫利昔单抗均耐药的RA患者。未观察到有益的临床效果。研究膝关节注射前的关节镜活检显示有TNFα染色，但免疫组织化学也证实存在淋巴毒素α（LTα或TNFβ）。随后使用依那西普（可阻断LTα以及TNFα）治疗导致疾病临床缓解。
结论
该病例表明，当TNFα不是主要的炎性细胞因子时，可能会出现对TNF阻断的耐药性，并提示LTα可能在RA中具有致病作用。
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