血清IgG4水平在IgG4相关性疾病及与风湿免疫性疾病鉴别诊断中的应用价值

Value of serum IgG4 in diagnosis of IgG4-related disease and in differentiation from rheumatic diseases

目的评价血清IgG4水平在诊断IgG4相关性疾病及与风湿免疫性疾病鉴别诊断中的应用价值。方法选择2010年1月至2011年11月在第二军医大学长海医院住院治疗的IgG4相关性疾病（IgG4-RD）患者23例。风湿免疫性疾病502例，包括干燥综合征26例，强直性脊柱炎50例，系统性硬化症3例，类风湿性关节炎（RA）125例，混合性结缔组织病15例，系统性红斑狼疮（SLE）212例，成人Still病20例，白塞病17例，多发性肌炎12例，皮肌炎12例，风湿性多肌痛10例。通过免疫散射比浊法测定血清IgG及IgG4水平。以IgG4-RD患者血清IgG4测定值绘制ROC曲线，确定血清IgG4临界值，以评价血清IgG4水平诊断IgG4-RD的敏感度、特异度。结果IgG4-RD患者血清~gC．4浓度为11．4（5．0～14．8）g／L，IgG4增高〉1．4g／L的比率为95．6％，与风湿免疫性疾病各组（干燥综合征组、强直性脊柱炎组、系统性硬化症组、RA组、混合性结缔组织病组、SLE组、成人Still病组、白塞病组、多发性肌炎组、皮肌炎组、风湿性多肌痛组）差异有统计学意义（U值分别为：6．0、21．0、0、58．5、0、9．0、3．0、4．0、0、3．0、3．5，P均〈0．01）。RA组血清IgG4水平[0．6（0．3～1．2）g／L]与SLE组[0．2（0．1～0．4）g／L]的差异有统计学意义（U=5847，P〈0．01）。风湿免疫性疾病各组部分患者血清也出现IgCA水平升高，其中RA、强直性脊柱炎、成人Still病、干燥综合征和风湿性多肌痛的升高比率〉10％。经ROC曲线分析，确定诊断IgG—RD[自身免疫性胰腺炎（AIP）]的血清IgG4最佳临界值为2．2g／L，其敏感度和特异度分别为95．7％和97．4％，曲线下面积（AUC）为0．995。以血清IgG42．2g／L为临界值，诊断IgG4-RD的敏感度和特异度无变化，但在风湿免疫性疾病各组中血清IgG4升高的比例明显降低，除风湿性多肌痛外，升高比率均〈10％，鉴别诊断的特异度显著上升。结论血清IgG4升高不是IgG4-RD所特异的，不能仅依靠血清IgG4的升高来诊断IgG4-RD。以2．2g／L作为血清IgG4升高的临界值能较好地对IgG4-RD进行诊断，并与风湿免疫性疾病进行鉴别诊断，但还需在临床进一步验证予以确定。

Objective To investigate the value of serum IgCA in diagnosis of IgG4-RD and in differentiation from rheumatic diseases. Methods Total of 23 patients with IgG4-RD and 502 patients with rheumatic diseases were enrolled, who presented at Changhai Hospital in 2010 to 2011. In the study, rheumatic diseases were categorized into groups of Sjogren syndrome （ n = 26 ）, ankylosing spondylitis （ n = 50 ） , systemic sclerosis （ n = 3 ）, rheumatoid arthritis （ RA, n = 125） , mixed connective tissue disease （ n = 15 ）, systemic lupus erythematosus （ SLE, n = 212 ）, adult onset still disease （ n = 20 ）, Behcet syndrome （ n = 17 ）, polymyositis （ n = 12 ）, dermatomyositis （ n = 12 ）, polymyalgiarheumatica （ n = 10）. Serum IgG and IgG4 levels were measured by a rate nephelometer assay. The ROC curves were constructed to identify the optimal serum IgG4 cutoff value for diagnosing IgG4-RD and evaluate its sensitivity and specificity. Results The mean levels of serum IgG4 in the group with IgG4-RD were 11.4（5.0-14. 8 ） g/L. In about 95.6% IgG4-RD patients, the serum IgG4 level was higher than 〉 1.4 g/L and other rheumatic diseases （ U values were 6. 0,21.0,0,58. 5,0,9. 0,3. 0,4. 0,0,3.0,3. 5,P 〈0. 01 ）. The levels of serum IgG4 with RA was 0. 6（0. 3-1.2） g/L, the levels of serum IgG4 with SLE was 0. 2（0. 1-0. 4） g/L. There were statistical differences between RA and SLE （ U value was 5847, P 〈 0. 01 ）. At the same time, some patients with other rheumatic diseases were found serum IgG4 level higher than 〉 1.4 g/L, which was about 10% in the patients whith RA, ankylosing spondylitis, adult onset still disease and polymyalgiarheumatica. According to the ROC constructed the cut off value in present study was 2. 2 g/L, and sensitivity and specificity were 95.7% and 97.4% , respectively. Area under the curve （AUC） was 0. 995. There were no significant differences between the sensitivity and specificity values obtained with a cutoff value of 2. 2 g/L. In patients with other rheumatic diseases, the ratio of high serum IgG4 level （ 〉 2.2 g/L） were declined obviously, except polymyalgiarheumatica, it was less than 10%. For differentiation from rheumatic diseases specificity values were higher. Conclusions The cut off value of 2. 2 g/L is useful for diagnosing IgG4-RD, and in differentiation from rheumatic diseases. The high serum IgG4 concentrations are not specific to IgG4- RD. The cut off value of 2. 2 g/L is better to diagnose IgG4-RD, and contributes to the differential diagnosis of IgG4-RD and other rheumatic diseases, but it needs to be further confirmed in clinical practice.