Anti-cyclic citrullinated peptide antibodies are a collection of anti-citrullinated protein antibodies and contain overlapping and non-overlapping reactivities
Anti-cyclic citrullinated peptide antibodies are a collection of anti-citrullinated protein antibodies and contain overlapping and non-overlapping reactivities
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DOI：
10.1136/ard.2010.131102
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发表时间：
2011-01-01
影响因子：
27.4
通讯作者：
Toes, Rene E. M.
中科院分区：
文献类型：
--
作者：
Ioan-Facsinay, Andreea;el-Bannoudi, Hanane;Toes, Rene E. M.
目的抗瓜氨酸蛋白抗体（ACPA）和抗环瓜氨酸肽抗体（抗CCP）是类风湿关节炎的标志性抗体，在类风湿关节炎的发病机制中起重要作用。这些抗体通常在ELISA中以瓜氨酸化肽（例如，CCP 2）或蛋白质作为抗原进行检测。血清中抗CCP抗体的绝对浓度未知。虽然抗几种瓜氨酸化蛋白的抗体主要可以在抗CCP阳性血清中检测到，但目前尚不清楚抗CCP抗体是否实际上是ACPA。同样，它是未知的，在何种程度上不同的瓜氨酸抗原的抗体反应是crossreactive.Methods建立了亲和纯化方法，其中瓜氨酸抗原特异性抗体从ELISA板洗脱，然后用于检测其他瓜氨酸抗原在ELISA或蛋白质印迹。对于额外的交叉反应性研究，ELISA为基础的抑制试验进行与瓜氨酸或对照肽作为inhibitors.Results抗CCP IgG抗体的浓度估计为至少30 μ g/ml的患者与高抗CCP水平（> 1600 μ g/ml）。亲和纯化的抗CCP抗体能够识别瓜氨酸纤维蛋白原（cit-fib）和瓜氨酸髓鞘碱性蛋白（cit-MBP）的蛋白质印迹。此外，cit-fib和cit-MBP特异性抗体具有交叉反应性。然而，额外的交叉反应性研究表明，瓜氨酸肽的非重叠抗体反应也可以存在于patients.Conclusions本报告首次显示，抗CCP抗体识别多种瓜氨酸蛋白，因此是一个集合的ACPA。更重要的是，这些数据表明，不同的ACPA反应是交叉反应，但交叉反应是不完全的，因为不同的非交叉反应反应也可以在RA患者中检测到。
Objective Anti-citrullinated protein antibodies (ACPA) and anti-cyclic citrullinated peptide (anti-CCP) antibodies are a hallmark of rheumatoid arthritis and are believed to play a role in disease pathogenesis. These antibodies are typically detected in ELISA with citrullinated peptides (eg, CCP2) or proteins as antigens. The absolute concentration of anti-CCP antibodies in serum is unknown. Although antibodies to several citrullinated proteins can mainly be detected within anti-CCP-positive sera, it is currently unknown whether anti-CCP antibodies are in fact ACPA. Likewise, it is unknown to what extent antibody responses to different citrullinated antigens are crossreactive.Methods An affinity purification method was established in which citrullinated antigen-specific antibodies were eluted from ELISA plates and then used for detection of other citrullinated antigens in ELISA or western blot. For additional crossreactivity studies, ELISA-based inhibition assays were performed with citrullinated or control peptides as inhibitors.Results The concentration of anti-CCP IgG antibodies was estimated to be at least 30 mu g/ml in patients with high anti-CCP levels (> 1600 mu g/ml). Affinity-purified anti-CCP antibodies were able to recognise citrullinated fibrinogen (cit-fib) and citrullinated myelin basic protein (cit-MBP) on western blot. Furthermore, antibodies specific for cit-fib and cit-MBP were crossreactive. However, additional crossreactivity studies indicated that non-overlapping antibody responses to citrullinated peptides can also exist in patients.Conclusions This report shows for the first time that anti-CCP antibodies recognise multiple citrullinated proteins and are thus a collection of ACPA. More importantly, the data indicate that different ACPA responses are crossreactive, but that crossreactivity is not complete, as distinct non-crossreactive responses can also be detected in patients with RA.