Russo K, Hoch S, Dima C, Varga J, Teodorescu M
Department of Microbiology/Immunology, College of Medicine, University of Illinois at Chicago, USA.
J Rheumatol. 2000 Jan;27(1):142-8.
To determine the disease sensitivity and specificity of testing for autoantibodies against 2 of the 3 main human centromere antigenic components, CENP-A and CENP-B (recombinant, expressed in baculovirus).
ELISA with CENP-A and CENP-B antigens were used to test 45 sera showing a centromere pattern by immunofluorescence (IFA) and sera from 96 patients with systemic sclerosis (SSc), subdivided into diffuse (dSSc) and limited (lSSc) forms. For controls, the same tests were performed on sera from 100 patients with rheumatoid arthritis (RA), 100 with systemic lupus erythematosus (SLE), and 50 random blood donors. Sera from all the patients with SSc were also tested for the presence of anti-Scl70 antibody by ELISA (bovine antigen), and for pattern and titer by IFA (HEp-2 cells).
Of the 45 IFA positive sera, 93% were positive for anti-CENP-A and 91% for anti-CENP-B. There was a very good quantitative correlation between the antibody levels against these 2 centromere components (r = 0.597; p<0.001). Anti-CENP-A and B were found in 48% of patients with lSSc, and in 11% and 9%, respectively, of those with dSSc. The difference in the frequency of anti-CENP-A between the 2 patient groups was significant (chi-squared, p<0.001). Similar levels of anticentromere staining pattern by IFA were observed for these 2 groups. Anti-Scl70 was elevated in 8% of lSSc and 25% of dSSc patients; this difference was also significant (chi-squared, p = 0.02). Neither CENP-A nor CENP-B reacted with IgG from SSc patients containing anti-Scl70. The frequency of abnormal levels in patients with SLE and RA was, respectively, 11% and 3% for anti-CENP-A and 4% and 3% for anti-CENP-B. The reaction of IgG from SLE and RA patients with CENP-A was not inhibited by histone H3, i.e., it was not due to recognition of the histone-like domain in CENP-A. Thus, when 96 SSc patients were compared to 200 patients with RA and SLE, the disease specificity of anti-CENP-A and B was 93% and 96.5%, respectively.
In addition to IFA, ELISA tests for CENP-A and CENP-B yield results with similar sensitivity and specificity for the diagnosis of SSc. CENP-A and CENP-B are primarily associated with lSSc. In SSc the autoantibody response is directed simultaneously and with similar amplitude against these 2 components of the centromere structure, whereas in other autoimmune diseases the response is directed mainly against one of the 2 components.
确定针对人类3种主要着丝粒抗原成分中的2种（CENP - A和CENP - B，杆状病毒中重组表达）进行自身抗体检测的疾病敏感性和特异性。
采用含CENP - A和CENP - B抗原的ELISA法检测45份经免疫荧光法（IFA）显示着丝粒模式的血清以及96例系统性硬化症（SSc）患者的血清，SSc患者又分为弥漫型（dSSc）和局限型（lSSc）。作为对照，对100例类风湿关节炎（RA）患者、100例系统性红斑狼疮（SLE）患者的血清以及50名随机献血者的血清进行同样检测。所有SSc患者的血清还用ELISA法（牛抗原）检测抗Scl70抗体的存在情况，并用IFA法（HEp - 2细胞）检测其模式和滴度。
45份IFA阳性血清中，93%抗CENP - A阳性，91%抗CENP - B阳性。针对这2种着丝粒成分的抗体水平之间存在非常好的定量相关性（r = 0.597；p<0.001）。lSSc患者中48%检测到抗CENP - A和抗CENP - B，dSSc患者中分别为11%和9%。两组患者抗CENP - A频率差异有统计学意义（卡方检验，p<0.001）。两组患者IFA检测的着丝粒染色模式水平相似。8%的lSSc患者和25%的dSSc患者抗Scl70升高；此差异也有统计学意义（卡方检验，p = 0.02）。CENP - A和CENP - B均不与含抗Scl70的SSc患者IgG反应。SLE和RA患者中抗CENP - A异常水平的频率分别为11%和3%，抗CENP - B分别为4%和3%。SLE和RA患者的IgG与CENP - A的反应不受组蛋白H3抑制，即不是由于识别CENP - A中的组蛋白样结构域。因此，当将96例SSc患者与200例RA和SLE患者比较时，抗CENP - A和抗CENP - B的疾病特异性分别为93%和96.5%。
除IFA外，针对CENP - A和CENP - B的ELISA检测在SSc诊断中具有相似的敏感性和特异性。CENP - A和CENP - B主要与lSSc相关。在SSc中，自身抗体反应同时且以相似幅度针对着丝粒结构的这2种成分，而在其他自身免疫性疾病中，反应主要针对这2种成分中的一种。
