血清IgG4、IgG4/IgG比值和IgG4/IgG1比值在米库利兹病诊断中的价值

Values of serum IgG4, IgG4/IgG ratio, and IgG4/IgG1 ratio in the diagnosis of Mikulicz′s disease

目的评价血清IgG4、IgG4/IgG比值和IgG4/IgG1比值鉴别诊断米库利兹病（MD）和原发性干燥综合征（pSS）的价值。方法回顾性研究2012年7月至2016年7月在北京大学人民医院进行IgG亚类检测的186例患者，包括42例米库利兹病患者和144例原发性干燥综合征患者。血清IgG亚类检测采用德国西门子公司BNⅡ仪器及其免疫散射比浊法试剂。部分患者同时使用间接免疫荧光法进行血清抗核抗体（ANA）的检测，使用免疫印迹法进行血清抗SSA抗体和抗SSB抗体的检测。定量资料采用中位数（四分位距）的方式表示，两组间的比较采用Mann-Whitney U检验。分类变量采用百分比表示，使用卡方检验。以pSS组为对照，分别以MD患者的血清IgG4、IgG4/IgG比值和IgG4/IgG1比值绘制ROC曲线，确定最佳临界值及曲线下面积（AUC）。结果MD组的血清IgG4、IgG4/IgG比值、IgG4/IgG1比值的中位数分别为11 200 mg/L（17 330）、0.444（0.314）和1.318 （1.920），高于pSS组的相应中位数329 mg/L（490）、0.016（0.025）和0.023 （0.039），差异有统计学意义（Z分别为－9.368、－9.560和－9.571，P均〈0.001）。ROC曲线分析显示以pSS组为对照时，血清IgG4、IgG4/IgG比值和IgG4/IgG1比值诊断MD的最佳临界值分别为1 870 mg/L、0.111和0.206，相应的AUC分别为0.976、0.985和0.986。AUC比较显示，血清IgG4/IgG比值和IgG4/IgG1比值的AUC相比，差异无统计学意义（Z＝0.283，P＝0.777），均高于血清IgG4的AUC（Z分别为2.360和1.975，P分别为0.018和0.048）。MD组血清ANA、抗SSA抗体和抗SSB抗体的阳性率分别为10%、6.7%和0%，低于PSS组的85.8%、72.3%和38.3%（χ^2＝71.340、44.773、16.792，P均〈0.001）。结论对于鉴别诊断MD和pSS，检测血清IgG4、IgG4/IgG比值和IgG4/IgG1比值均具有重要的价值，血清IgG4/IgG比值或IgG4/IgG1比值的诊断性能优于IgG4。

ObjectiveTo evaluate values of Serum IgG4, IgG4/IgG ratio, and IgG4/IgG1 ratio for distinguishing Mikulicz′s disease （MD） from primary Sj？gren′s syndrome （pSS）.MethodsIt retrospectively analyzed 186 patients subjected to serum IgG subclass testing to differentiate MD from primary Sj？gren′s syndrome （pSS） at Peking University People′s Hospital from July 2012 to July 2016. This sample included 42 MD patients and 144 pSS patients. Serum IgG subclass concentrations were measured using Siemens reagents with nephelometry and BNⅡ instrument. In partial patients, serum antinuclear antibodies （ANA） were detected by indirect immunofluorescence assay, and serum anti-SSA antibodies and anti-SSB antibodies were detected by Western blot. Serum IgG subclass test results, ANA test results, serum anti-SSA antibody, and anti-SSB antibody test results were collected. The quantitative data were represented by median （quantile range）. The Mann-Whitney U test was used to compare the medians between the two groups. Categorical variables were analyzed with a χ2 test and were shown as percentages. The ROC curve was constructed to identify the optimal cut-off values and the area under the curve （AUC） values of the serum IgG4, IgG4/IgG ratio, and IgG4/IgG1 ratio for distinguishing MD patients from pSS patients.ResultsThe medians of serum IgG4, IgG4/IgG ratio and IgG4/IgG1 ratio in MD patients were 11 200 mg/L （17 330）, 0.444 （0.314） and 1.318 （1.920）, as compared with 329 mg/L （490） , 0.016 （0.025） and 0.023 （0.039） respectively in pSS patients （Z=-9.368, -9.560, and -9.571, respectively, P〈0.001）. For distinguishing MD from pSS, the optimal cut-off values of serum IgG4, IgG4/IgG ratio, and IgG4/IgG1 ratio were 1 870 mg/L, 0.111, and 0.206, respectively. The corresponding AUC values were 0.976, 0.985, and 0.986, respectively. Comparison of the ROC curves showed that there was no significant difference between AUC of serum IgG4/IgG ratio and IgG4/IgG1 ratio （Z=0.283, P=0.777）. But AUC of serum IgG4/IgG ratio and IgG4/IgG1 ratio were significantly higher than AUC of serum IgG4 （Z=2.360 and 1.975, repectively, P=0.018 and 0.048, respectively）. The positive rates of serum ANA in MD and pSS group were 10% and 85.8%, respectively （χ^2=71.340, P〈0.001）. The positive rates of anti-SSA antibody and anti-SSB antibody in MD were 6.7% and 0%, respectively. Compared to 72.3% and 38.3% in pSS group, they were lower （χ^2 =44.773 and 16.792, P〈0.001）.ConclusionsMeasurements of serum IgG4 concentration, IgG4/IgG ratio, and IgG4/IgG1 ratio were of important values in differentiating MD from pSS. Serum IgG4/IgG ratio or IgG4/IgG1 ratio was superior to serum IgG4.