抗核抗體與可抽取核抗原之抗體用於診斷自體免疫疾病的表現

Performance of antinuclear antibody and anti-extractable nuclear antigen antibody tests in the diagnosis of autoimmune diseases

背景：分析抗核抗體與抗可抽取核抗原之抗體用於診斷自體免疫疾病的敏感度、特異度、陽性預測值、陰性預測值、陽性概似比以及陰性概似比。方法：我們收集長庚醫院2010年12月至2011年2月之間至風濕免疫科門診就診並接受anti-ENA及ANA抗體分析的400位病患，追蹤六個月以上之病歷，做回顧性分析。結果：於400位病患中，189（47.3%）位歸類於自體免疫疾病組，另外211（52.7%）位病患歸類於非自體免疫疾病組。ANA的切點若設在1:160，則用於自體免疫疾病的偵測之敏感度為69%，特異度為82%，陽性預測值為77%，陽性概似比為3.72；Anti-ENA抗體於自體免疫疾病的偵測之敏感度為59%，特異度為89%，陽性預測值為82%，陽性概似比為5.21。ANA的切點若設在1:640則可獲得極佳的陽性預測值（91%）以及較好的陽性概似比（11.04）。於自體免疫疾病組，有59位病患的ANA ≤1:80，而當中有高達32.2%的病患anti-ENA抗體呈陽性。結論：ANA對於自體免疫疾病是個篩檢工具，不過若ANA的切點設在1:640則對於自體免疫疾病享有極佳的診斷正確率。一般說來，ANA檢驗於診斷自體免疫疾病有較高的敏感度，若呈陰性則有助於排除診斷；而anti-ENA抗體的檢驗則有較高的特異度，亦擁有較高的陽性預測值以及較高的陽性概似比，可用於確定診斷自體免疫疾病之輔助。ANA與anti-ENA抗體的檢驗有互補的效果，若能共同偵測則可提升診斷正確率。對於ANA陰性或弱陽性但臨床上懷疑有自體免疫疾病的個案，仍然建議要接著檢驗anti-ENA抗體。

Background: This study aimed to investigate the sensitivity, specificity, positive predictive values (PPV), negative predictive values (NPV), positive likelihood ratio (LR+) and negative likelihood ratio (LR-) of antinuclear antibody (ANA) and anti-extractable nuclear antigen antibody (anti-ENA) tests in the diagnosis of autoimmune diseases (AID). Materials and Methods: Patients who visited Chang Gung Memorial Hospital Rheumatology outpatient department and for whom both ANA and anti-ENA tests were performed from December 2010 to February 2011 were enrolled in this study. The clinical data of 400 subjects were recorded and analyzed. All study subjects were followed for at least 6 months. Results: Of the 400 subjects, 189 (47.3%) were classified as AID group; 211 (52.7%) were classified as the non-autoimmune disease (non-AID) group. In the diagnosis of AID, the sensitivity, specificity, PPV and LR+ of the ANA test at titer of ≥1:160 were 69%, 82%, 77%, and 3.72, respectively; the sensitivity, specificity, PPV and LR+ of the anti-ENA test were 59%, 89%, 82%, and 5.21, respectively. The ANA test had excellent PPV (91%) and good LR+ (11.04) at the cutoff titer of ≥1:640. Among the 59 patients in the AID group with traditional normal cutoff ANA titer of ≤1:80, as many as 32.2% (19 out of 59) of the patients had positive anti-ENA antibodies. Conclusions: ANA is traditionally a screening tool for AID, however, a positive ANA test at a cutoff titer of 1:640 has good diagnostic accuracy for AIDs. However, due to the relatively higher sensitivity and higher negative predictive value for detecting AIDs, a negative ANA test is intended for diagnostic exclusion; due to a relatively higher positive likelihood ratio and a higher positive predictive value, a positive anti-ENA test is complementary to ANA and both are useful in detecting AIDs. The results of the ANA test and subsequent follow-up or concomitant anti-ENA testing are key pieces to making the clinical diagnosis. In cases presenting with clinical symptoms or signs of AIDs but with negative ANA results or a lower titer of ANA, further screening for associated anti-ENA antibodies is recommended.