致密细斑点型抗核抗体在自身免疫性疾病中的临床意义

Clinical significance of antinuclear antibodies associated with the nuclear dense fine speckled immunofluorescence pattern in autoimmune disease

目的探讨致密细斑点型（DFS）抗核抗体在抗核抗体（ANA）常规检测者中的阳性分布及其在自身免疫性疾病（AID）中的相关临床意义。方法回顾性研究。收集201l至2014年温州医科大学附属温岭医院就诊患者13728例，采用间接免疫荧光法（IIF）检测ANA临床标本中的DFS的结果。计算DFS在临床就诊患者中的阳性检出率，统计DFS阳性的AID患者中的相关临床信息和实验室特征。阳性率比较采用卡方检验。结果在13728例患者ANA常规检测中，ANA阳性为2822例，阳性率20．56％。其中DFS阳性为248例，占所有ANA常规检测的1．81％，在ANA阳性者中的阳性率为8．79％。男、女性者在不同年龄组（≤20岁组、21-49岁组、≥50岁组）问的DFS阳性率均有统计学意义（X^2=18．17、1500．00，P均〈0．01），以≥50岁组的DFS阳性率为最高。ANA阳性检出率以风湿免疫科中最高（30．07％），但ANA阳性中的DFS主要见于感染科（32．58％）、皮肤科（21．76％）、神经科（18．58％）、肾内科（6．73％）等，且科室间的阳性率差异有统计学意义（X^2=123．00，P〈0．01）。248例DFS阳性者中，包括41例AID患者（16．53％），207例非AID患者（83．47％）。其中系统性AID中以类风湿关节炎患者构成比最高（29．27％），器官特异性AID中以自身免疫性甲状腺炎患者构成比最高（31．71％）。DFS阳性滴度1：100在非AID患者中的阳性率高于AID者（X^2=6．20，P〈0．05）；DFS阳性滴度1：320则在AID患者中的阳性率高于非AID者（）（2=5．38，P〈0．05）。DFS阳性的AID患者存在不同程度的临床表现，而实验室以抗核抗体谱（ANAs）中的15项特异性抗体均阴性为主要特征。结论DFS是ANA阳性者中的常见荧光模式，在ANA阳性者中存在不同的性别、年龄问差异；DFS阳性者主要出现在非AID患者中；对于DFS阳性者需进一步检测其特异性的抗DFS70抗体。

Objective To explore the prevalence of the nuclear dense fine speckled （DFS） immunofluorescence pattern in routine antinuclear antibodies （ANA） testing and its significance in patients with autoimmune diseases（AID）. Methods The ANA in 13 728 specimens were measured by indirect immunofluorescence（IIF） using HEp-2 cell slides from department of clinical laboratory, wenling hospital from 2011 to 2014. The frequencies, clinical manifestations and laboratory features of DFS positivity were restrospectively analyzed in patients with AID,using X^2 test. Results ANA was positive in 20. 56% （2 822/ 13 728 ） of the total patients, and the frequency of DFS pattern was observed in 1.81% （248/13 728 ） of the total patients and in 8.79% （248/2 822） of the patients with ANA positivity. In different age groups （ ≤20 years old, 21 -49 years old and ≥50 years old） , there were statistical significance of DFS pattern positive rate （ male ： X^2 = 18.17, P 〈 O. 01 ; female ： X2 = 1 500. 00, P 〈 0. 01 ）. And the highest frequency of ANA positivity was observed in patients from department of rheumatology（ 30. 07 % ）. The frequency of DFS pattern was higher in the departments of infection （ 32.58% ） , dermatology （ 21.76% ） , neurology （ 18.58% ） and nephrology（6. 73% ） among the patients with ANA positivity （X^2 = 123. O0,P 〈 0. 01 ）. Amony the 248 cases with DFS pattern positivity. 41 cases were AID （16. 53% ） and 207 cases were non- autoimmune diseases（83.47% ）. In AID group 13 cases were autoimmune tbyroiditis （31.71%）, 12 cases were rheumatoid arthritis （29.27%）, 4 cases were autoimmune liver disease （9.76%）, 4 cases were undifferentiated connective tissue disease （9. 76% ） , 3 cases were ankylosing spondylitis（7.32% ） , 2 cases were Sjfigren＇s disease （4. 88% ）, 2 cases were inflammatory bowel disease （4. 88%） and 1 case was systemic lupus erythematosus（2.44% ）. The titers of DFS in patients with AID were predominantly above 1 ：320 and less than 1：100 in non-AID. AID patients with DFS pattern positivity have different clinical manifestations and laboratory features. Howerer, antinuclear antibodies （ANAs） in 15 specific auto- antibodies were all negative. Conclusions The DFS pattern is a common pattern in ANA positivity patients and it mainly exists in non-AID patients. Further more, it is suggested that patients with DFS pattern identified by IIF should then be tested for anti-DFS70 antibodies with a specific immunoassay. （Chin J Lab Med,2015,38：173-177）