Benucci Maurizio, Saviola Gianantonio, Baiardi Paola, Cammelli Emanuela, Manfredi Mariangela
Rheumatology Unit, Nuovo Ospedale S. Giovanni di Dio, ASL 10, via di Torregalli 3, Florence, Italy.
Clin Rheumatol. 2008 Jan;27(1):91-5. doi: 10.1007/s10067-007-0728-5. Epub 2007 Oct 10.
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.
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。