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抗核小体抗体作为类风湿关节炎中三种不同肿瘤坏死因子α阻断剂治疗期间自身抗体产生的预测因子。

Anti-nucleosome antibodies as prediction factor of development of autoantibodies during therapy with three different TNFalpha blocking agents in rheumatoid arthritis.

作者信息

Benucci Maurizio, Saviola Gianantonio, Baiardi Paola, Cammelli Emanuela, Manfredi Mariangela

机构信息

Rheumatology Unit, Nuovo Ospedale S. Giovanni di Dio, ASL 10, via di Torregalli 3, Florence, Italy.

出版信息

Clin Rheumatol. 2008 Jan;27(1):91-5. doi: 10.1007/s10067-007-0728-5. Epub 2007 Oct 10.

Abstract

Anti-nucleosome antibodies have a role in the diagnosis and follow-up of systemic lupus erythematosus (SLE) and have a possible correlation with SLE activity and with kidney and hematological involvement. The aim of our study was to detect in 91 patients with rheumatoid arthritis (RA) the positivity of anti-nucleosome antibodies during therapy with three different TNFalpha blocking agents and to underline the possible correlation with the development of antinuclear autoantibodies (ANA) and anti-dsDNA autoantibodies. We detected anti-nucleosome antibodies, ANA, and anti-dsDNA during therapy with three different TNFalpha blocking agents at T-0 and after 12 and 24 weeks of treatment, respectively. Anti-nucleosome antibodies (IgG class) were analyzed by ELISA technique (Orgentec Diagnostika GmbH, Mainz, Germany), ANA both by indirect immunofluorescence (IIF) technique on Hep-2 (Scimedx, USA) and by ELISA (Autoimmune EIA ANA screening test Bio-Rad Laboratories, CA, USA), and anti-dsDNA (IgG and IgM classes) by ELISA (Kallestad, Bio-Rad Laboratories, CA, USA) and confirmed by IIF on Crithidia luciliae (ImmunoConcepts N.A., Sacramento, CA, USA). We observed 19 patients on infliximab treatment at 3 mg/kg every 8 weeks, 43 patients on etanercept treatment at 25 mg twice a week, and 29 patients on adalimumab treatment at 40 mg every other week. At baseline, we observed positivity as follow: in the group of patients treated with infliximab-anti-nucleosome 1/19 (5.26%), ANA 3/19 (15.7%), anti-dsDNA 1/19 (5.26%); in the group treated with etanercept--anti-nucleosome 2/43 (4.65%), ANA 1/43 (2.43%), anti-dsDNA 0/43; and in the group treated with adalimumab--anti-nucleosome 2/29 (6.89%), ANA 1/29 (3.44%), anti-dsDNA 0/29. The results at 12 weeks for the three autoantibodies were: for infliximab--3/19 (15.7%), 10/19 (52.6%), 2/19 (10.5%); for etanercept--3/43 (6.9%), 10/43 (23.2%), 1/43 (2.32%); and for adalimumab--3/29 (10.3%), 4/29 (13.7%), 1/29 (3.4%). At 24 weeks, the results were for infliximab 6/19 (31.5%), 12/19 (63.1%), 2/19 (10.5%); for etanercept 11/43 (25.5%), 22/43 (51.1%), 2/43 (4.65%); and for adalimumab 4/29 (13.7%), 13/29 (44.8%), 1/29 (3.4%). We observed a concordance anti-nucleosome/ANA antibodies of 85.5% (p < 0.001). Our data showed a concordance between anti-nucleosome antibodies and ANA positivity in patients with RA during therapy with TNFalpha blocking agents. The induction of autoantibodies positivity is different for each TNFalpha blocking agent.

摘要

抗核小体抗体在系统性红斑狼疮(SLE)的诊断及随访中发挥作用,并且可能与SLE活动以及肾脏和血液系统受累相关。我们研究的目的是检测91例类风湿关节炎(RA)患者在接受三种不同肿瘤坏死因子α(TNFα)阻断剂治疗期间抗核小体抗体的阳性情况,并强调其与抗核抗体(ANA)和抗双链DNA(dsDNA)自身抗体产生之间可能存在的相关性。我们分别在T-0以及治疗12周和24周后,检测了三种不同TNFα阻断剂治疗期间患者的抗核小体抗体、ANA和抗dsDNA。采用酶联免疫吸附测定(ELISA)技术(德国美因茨奥根泰克诊断有限公司)分析抗核小体抗体(IgG类),采用间接免疫荧光(IIF)技术(美国Scimedx公司的Hep-2)和ELISA(美国加利福尼亚州Bio-Rad实验室的自身免疫EIA ANA筛查试验)检测ANA,采用ELISA(美国加利福尼亚州Bio-Rad实验室的Kallestad)检测抗dsDNA(IgG和IgM类),并通过在亮绿锥虫上进行IIF(美国加利福尼亚州萨克拉门托免疫概念公司)进行确认。我们观察到19例患者接受英夫利昔单抗治疗,剂量为每8周3mg/kg;43例患者接受依那西普治疗,剂量为每周两次25mg;29例患者接受阿达木单抗治疗,剂量为每隔一周40mg。基线时,我们观察到的阳性情况如下:在接受英夫利昔单抗治疗的患者组中,抗核小体1/19(5.26%),ANA 3/19(15.7%),抗dsDNA 1/19(5.26%);在接受依那西普治疗的患者组中,抗核小体2/43(4.65%),ANA 1/43(2.43%),抗dsDNA 0/43;在接受阿达木单抗治疗的患者组中,抗核小体2/29(6.89%),ANA 1/29(3.44%),抗dsDNA 0/29。三种自身抗体在12周时的结果分别为:英夫利昔单抗组——抗核小体3/19(15.7%),ANA 1/(52.6%),抗dsDNA 2/19(10.5%);依那西普组——抗核小体3/43(6.9%),ANA 10/43(23.2%),抗dsDNA 1/43(2.32%);阿达木单抗组——抗核小体3/29(10.3%),ANA 4/29(13.7%),抗dsDNA 1/29((3.4%)。在24周时,结果分别为:英夫利昔单抗组6/19(31.5%),ANA 12/19(63.1%),抗dsDNA 2/19(10.5%);依那西普组11/43(25.5%),ANA 22/43(51.1%),抗dsDNA /43(4.65%);阿达木单抗组4/29(13.7%),ANA 13/29(44.8%),抗dsDNA 1/29(3.4%)。我们观察到抗核小体/ANA抗体的一致性为85.5%(p<0.001)。我们的数据显示,在RA患者接受TNFα阻断剂治疗期间,抗核小体抗体与ANA阳性之间存在一致性。每种TNFα阻断剂诱导自身抗体阳性的情况有所不同。

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