抗 MCV 抗体对强直性脊柱炎的诊断价值

摘要

Objective To investigate the diagnostic value of anti-mutated citrullinated vimentin (anti-MCV) and anti-cyclic citrullinated peptide (anti-CCP) antibodies for ankylosing spondylitis (AS), and to establish a new diagnostic method of AS based on anti-citrullinated protein/peptide antibodies (ACPAs) detection.Methods Totally 121 AS patients(AS group), 97 rheumatoid arthritis(RA) patients (RA group)and 103 healthy people(control group) were enrolled for the detection of serum levels of anti-MCV and anti-CCP antibodies using ELISA method as a diagnostic test .HLA-B27 in AS patients was tested by flow cytometry , and RF-IgM in RA and AS patients was detected by immune rate nephelometry .Receiver operating characteristics ( ROC) curve was used to analyze the diagnostic value and to determine the cut-off value.Anti-MCV and anti-CCP antibodies among each group were compared by Mann-Whitney U test, Chi-square test or Fisher′s exact test was used to compare positive rate .Results The anti-MCV levels in AS group [11.60 ( 12.36-25.83 ) U/ml ] were significantly higher than control group [ 11.60 ( 8.41 -13.54)U/ml ],U=2 413,P <0.001, while the levels of anti-CCP had no difference between the two groups [AS group 6.22 (4.30 -8.07) U/ml], and control group [6.01 (3.77 -7.58) U/ml], respectively;U=5 421,P=0.094.The calculated area under the ROC curve of anti-MCV was 0.806,and 14.67 U/ml was the optimal cut-off value with sensitivity of 0.645 and specificity of 0.942.In both HLA-B27 positive and negative AS patients , anti-MCV antibodies levels and positive rate were significantly higher than control group using new cut-off value above (U =133.5, P =0.001; U =2 279.5,P <0.001). Sensitivity of the combination detection of anti-MCV and anti-CCP ( MCV+CCP-) or RF-IgM ( MCV+RF-) were 60.3%(73/121), 62.8% (76/121) and specificity were 89.7% (87/97), 90.7% (88/97) respectively in differential diagnosis of AS and RA , which were significantly higher than anti-MCV detection alone in specificity (16.5%,16/97).Conclusions Anti-MCV could be a new biomarker for the diagnosis of AS .With high sensitivity and specificity , anti-MCV has an equal diagnostic efficiency in HLA-B27 positive and negative AS patients using our new cut-off value.Additionally, the combination detection of anti-MCV and anti-CCP or RF-IgM could be an effective method for differential diagnosis of AS and RA .%目的：探讨抗突变型瓜氨酸波形蛋白（MCV）抗体和抗环瓜氨酸肽（CCP）抗体对强直性脊柱炎（AS）的诊断价值，并建立基于抗瓜氨酸蛋白/肽抗体（ ACPAs）检测的新的AS诊断方法。方法通过诊断性研究，ELISA法检测121例AS患者（ AS组）、97例RA患者（ RA组）、103名健康体检者（健康对照组）血清抗MCV抗体及抗CCP抗体，流式细胞法检测AS患者淋巴细胞表面HLA-B27表达，速率散射免疫比浊法检测RA患者和AS患者血清类风湿因子IgM（RF-IgM），利用受试者工作特征（ ROC）曲线分析抗MCV抗体对AS的诊断价值，确定诊断临界值。各组间抗MCV抗体及抗CCP抗体比较采用非参数Mann-Whitney U检验，率的比较用χ2检验或Fisher 精确检验。结果AS组血清抗MCV抗体水平18.13（12.36～25.83） U/ml显著高于健康对照组11.60（8.41～13.54） U/ml（U＝2413，P＜0.001），而抗CCP抗体水平在两组间[AS组6.22（4.30～8.07）U/ml，健康对照组6.01（3.77～7.58）U/ml]差异无统计学意义（U＝5421，P＝0.094）；抗MCV抗体的ROC曲线下面积为0.806，14.67 U/ml为最佳的诊断临界值，采用此临界值，诊断敏感度为0.645，特异度为0.942，在HLA-B27阴性和阳性AS患者中，抗MCV抗体水平及阳性率均高于健康对照组（U＝133.5，P＝0.001；U＝2279.5，P＜0.001）；使用抗MCV抗体和抗CCP抗体、抗MCV抗体和RF-IgM联合检测鉴别诊断AS和RA的敏感度分别为60.3％（73/121）、62.8％（76/121），特异度分别为89.7％（87/97）、90.7％（88/97），特异度高于抗MCV抗体单独检测（16.5％，16/97）。结论抗MCV抗体可以作为一种新的AS血清诊断指标，确立的新AS诊断临界值具有高敏感度和特异度，且对不同HLA-B27状态的AS患者有同等的诊断效力，使用MCV抗体和抗CCP抗体（ MCV＋CCP-）或RF-IgM（ MCV＋RF-）联合检测分析可以有效对AS和RA进行鉴别诊断。（中华检验医学杂志，2014，37：455-458）