Wu R, Shovman O, Zhang Y, Gilburd B, Zandman-Goddard G, Shoenfeld Yehuda
Pathway Diagnostics Inc., Malibu, CA, USA.
Clin Rev Allergy Immunol. 2007 Feb;32(1):47-56. doi: 10.1007/BF02686081.
To investigate the prevalence of anti-third generation cyclic citrullinated peptide antibodies (anti-CCP3) in patients with systemic connective tissue diseases, we assembled a training set consisting of 115 patients with rheumatoid arthritis (RA), 52 with Calcinosis, Raynaud's phenomenon, oesophageal dysmotility, sclerodactyly, telangiectasia (CREST) syndrome, 21 with scleroderma, 20 with ankylosing spondylitis, 18 with reactive arthritis, 25 with juvenile rheumatoid arthritis (RA), 51 with osteoarthritis, 26 with mixed connective tissue disease, 23 with primary Sjogren's syndrome, 74 with systemic lupus erythematosus, 49 with Polymyalgia rheumatica, and 39 with polymyositis/dermatomyositis. The commercial enzyme-linked immunosorbent assay (ELISA) was used to detect anti-CCP antibodies, including anti-CCP2 (regular, second generation of CCP antigen) and anti-CCP3 (third generation of CCP antigen) in disease-related specimens and normal controls. These serum samples were also evaluated for anti-centomere antibodies by anti-centromere ELISA kit. The higher frequencies of anti-CCP3 and anti-CCP2 were detected in 75.6 and 70.4% patients with RA, respectively. At the same time, anti-CCP3 (not anti-CCP2) was significantly increased in samples isolated from patients with CREST syndrome. The clinical sensitivity of IgG anti-CCP3 for the patients with CREST syndrome was 29% (15 of 52) and the specificity was 96% (384 of 397), with the exception of the RA group. The anti-centromere antibodies were significantly higher in patients with CREST only. The results of our study suggest that compared to anti-CCP2 assay, the new anti-CCP3 assay can enhance the clinical sensitivity for diagnosis of RA and, as an associate marker combined with anticentromere, can distinguish CREST syndrome from other systemic connective tissue diseases, especially RA. The clinical specificity of anti-CCP3 was lower than anti-CCP2 assay in diagnosis of RA because of the crossreaction to the patients with CREST syndrome.
为了调查系统性结缔组织病患者中抗第三代环瓜氨酸肽抗体（抗CCP3）的患病率，我们组建了一个训练集，其中包括115例类风湿关节炎（RA）患者、52例钙质沉着、雷诺现象、食管动力障碍、指端硬化、毛细血管扩张（CREST）综合征患者、21例硬皮病患者、20例强直性脊柱炎患者、18例反应性关节炎患者、25例幼年类风湿关节炎（RA）患者、51例骨关节炎患者、26例混合性结缔组织病患者、23例原发性干燥综合征患者、74例系统性红斑狼疮患者、49例风湿性多肌痛患者以及39例多发性肌炎/皮肌炎患者。采用商业酶联免疫吸附测定（ELISA）法检测疾病相关标本和正常对照中的抗CCP抗体，包括抗CCP2（常规，第二代CCP抗原）和抗CCP3（第三代CCP抗原）。这些血清样本还通过抗着丝点ELISA试剂盒评估抗着丝点抗体。在RA患者中，分别有75.6%和70.4%的患者检测到较高频率的抗CCP3和抗CCP2。同时，从CREST综合征患者分离的样本中抗CCP3（而非抗CCP2）显著增加。IgG抗CCP3对CREST综合征患者的临床敏感性为29%（52例中的15例），特异性为96%（397例中的384例），RA组除外。仅CREST患者的抗着丝点抗体显著更高。我们的研究结果表明，与抗CCP2检测相比，新的抗CCP3检测可提高RA诊断的临床敏感性，并且作为与抗着丝点联合的标志物，可将CREST综合征与其他系统性结缔组织病，尤其是RA区分开来。由于与CREST综合征患者存在交叉反应，抗CCP3在RA诊断中的临床特异性低于抗CCP2检测。
