Kastbom Alf, Forslind Kristina, Ernestam Sofia, Geborek Pierre, Karlsson Johan A, Petersson Ingemar F, Saevarsdottir Saedis, Klareskog Lars, van Vollenhoven Ronald F, Lundberg Karin
Rheumatology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden Department of Rheumatology and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
Section of Rheumatology, Department of Medicine, Helsingborg's lasarett, Helsingborg, Sweden Section of Rheumatology, Department of Clinical Sciences, Skåne University Hospital, Lund, Sweden.
Ann Rheum Dis. 2016 Feb;75(2):356-61. doi: 10.1136/annrheumdis-2014-205698. Epub 2014 Dec 30.
To determine the relationship between changes in antibody levels towards citrullinated peptides derived from different candidate autoantigens and therapeutic outcome in early rheumatoid arthritis (RA).
Baseline and 3-month serum samples from 316 patients with early RA enrolled in the Swedish Farmacotherapy (SWEFOT) trial were analysed for antibodies against cyclic citrullinated peptides (CCP) and citrullinated peptides derived from vimentin (cVim), fibrinogen (cFib) and α-enolase (CEP-1). At 3-month follow-up, methotrexate monotherapy-inadequate responders were randomised to add-on therapy with sulfasalazine and hydroxychloroquine or infliximab. In these patients, anticitrullinated peptide antibodies (ACPA) were also assessed at 12 and 24 months. The proportion of antibody-positive patients and relative changes in antibody levels were compared across ACPA specificities and related to therapeutic response and radiographic progression.
During the 2-year follow-up, the proportion of patients testing positive declined significantly regarding antibodies to cVim, cFib and CEP-1, while anti-CCP antibody occurrence remained stable over time. Turning anti-cVim antibody negative was most common, and anti-cVim antibody seroreversion during the first three months associated with significantly less 2-year radiographic progression compared with patients who remained positive. Median antibody levels of all tested ACPAs declined uniformly during initial methotrexate therapy and following response to add-on therapy, with no significant relation to treatment regimen or radiographic progression.
The influence of early antirheumatic therapy on ACPA seroreversions was markedly different across specificities, and early disappearance of anti-cVim antibodies associated with better radiological outcome. Thus, these data suggest that the disappearance of particular ACPA reactivities may be beneficial in early RA.
WHO database at the Karolinska institute: CT20080004; and clinicaltrials.gov: NCT00764725.
确定早期类风湿关节炎（RA）患者针对不同候选自身抗原衍生的瓜氨酸化肽的抗体水平变化与治疗结果之间的关系。
对瑞典药物治疗（SWEFOT）试验中纳入的316例早期RA患者的基线和3个月时的血清样本进行分析，检测抗环瓜氨酸化肽（CCP）抗体以及抗波形蛋白衍生瓜氨酸化肽（cVim）、抗纤维蛋白原衍生瓜氨酸化肽（cFib）和抗α-烯醇化酶衍生瓜氨酸化肽（CEP-1）抗体。在3个月随访时，甲氨蝶呤单药治疗反应不佳的患者被随机分配接受联合柳氮磺吡啶和羟氯喹或英夫利昔单抗的附加治疗。在这些患者中，还在12个月和24个月时评估抗瓜氨酸化肽抗体（ACPA）。比较不同ACPA特异性的抗体阳性患者比例和抗体水平的相对变化，并与治疗反应和影像学进展相关联。
在2年随访期间，抗cVim、cFib和CEP-1抗体检测呈阳性的患者比例显著下降，而抗CCP抗体的出现率随时间保持稳定。抗cVim抗体转阴最为常见，与持续阳性的患者相比，前三个月抗cVim抗体血清学逆转的患者2年影像学进展显著更少。在初始甲氨蝶呤治疗期间及附加治疗有反应后，所有检测的ACPA的抗体水平中位数均一致下降，与治疗方案或影像学进展无显著关联。
早期抗风湿治疗对ACPA血清学逆转的影响在不同特异性之间明显不同，抗cVim抗体的早期消失与更好的放射学结果相关。因此，这些数据表明特定ACPA反应性的消失在早期RA中可能是有益的。
卡罗林斯卡学院世界卫生组织数据库：CT20080004；以及美国国立医学图书馆临床试验数据库：NCT00764725。
