抗SSB抗体阳性和阴性的原发性干燥综合征患者临床及免疫学特征的比较

Comparison of clinical and immunological characteristics between primary Sj gren’s syndrome patients with positive and negative anti-SSB antibody

目的:分析抗干燥综合征抗原B(Sj?gren’s syndrome type B,SSB)抗体阳性的原发性干燥综合征(primary Sjogren’s syndrome,pSS)患者与抗SSB抗体阴性的pSS患者之间临床表现及实验室指标的差异。方法:回顾性收集2009—2019年于北京大学第三医院风湿免疫科住院的pSS患者的病历资料,采用t检验、Mann-Whitney秩和检验、卡方检验和Fisher确切概率法对抗SSB抗体阳性和抗SSB抗体阴性的pSS患者组的临床特征及实验室指标进行分析。结果:共纳入pSS患者142例,其中女性137例,男性5例,平均年龄(54.8±13.3)岁,其中抗SSB抗体阳性患者44例(31.0%)。临床特征方面,抗SSB抗体阳性的pSS患者较抗体阴性患者的就诊年龄和起病年龄更小[就诊年龄:(50.9±14.5)岁vs.(56.5±12.4)岁,P<0.05;起病年龄:(42.2±14.8)岁vs.(49.5±15.3)岁,P<0.05],出现皮疹(29.5%vs.14.3%,P<0.05)、腮腺肿大(27.3%vs.8.2%,P<0.05)、肾小管酸中毒(15.9%vs.4.2%,P<0.05)、免疫性血小板减少(9.1%vs.1.0%,P<0.05)的比例更高;两组患者在口干、眼干、雷诺现象(Raynaud phenomenon)等方面差异无统计学意义。实验室指标方面,抗SSB抗体阳性组患者与阴性组患者相比,类风湿因子(rheumatoid factor,RF)阳性率(85.0%vs.49.4%,P<0.05)及滴度(中位数89.8 IU/mL vs.20.5 IU/mL,P<0.05)、抗核抗体(antinuclear antibody,ANA)滴度(中位数320 vs.160,P<0.05)、抗干燥综合征抗原A(Sjogren’s syndrome type A,SSA)抗体阳性率(97.7%vs.64.3%,P<0.05)、IgG水平(中位数21.0 g/L vs.15.6 g/L,P<0.05)、γ球蛋白升高率(71.4%vs.38.5%,P<0.05)、CD3^(-)CD19^(+)细胞比例[(21.0±11.9)%vs.(13.7±9.6)%,P<0.05]均更高,而CD3^(+)细胞比例[(67.2±14.4)%vs.(76.6±13.1)%,P<0.05]和抗线粒体抗体M2亚型阳性率(10.5%vs.35.6%,P<0.05)相对更低,其余无明显差异。治疗方面,与抗SSB抗体阴性组患者相比,抗SSB抗体阳性组患者应用激素(90.9%vs.73.5%,P<0.05)及免疫抑制剂(54.5%vs.36.7%,P<0.05)的比例更高。结论:与抗SSB抗体阴性pSS患者相比,抗SSB抗体阳性患者的起病年龄更小,临床表现更多样,血清其他自身抗体阳性率/水平及B细胞活化程度更高,治疗上需要应用激素及免疫抑制剂的概率更大,整体倾向于表现出更重的临床表型。

Objective:To analyze the differences of clinical manifestations and laboratory features between primary Sj gren’s syndrome(pSS)patients with positive and negative anti-Sj gren’s syndrome type B(SSB)antibody.Methods:The clinical data of pSS patients hospitalized in Department of Rheumato-logy and Immunology,Peking University Third Hospital were retrospectively analyzed to investigate the differences of clinical and laboratory features between anti-SSB positive and negative groups.The t test,Mann-Whitney U test,Chi-square test and Fisher’s exact probability were used for analysis.Results:A total of 142 pSS patients were enrolled in this study,including 137 females and 5 males with a mean age of(54.8±13.3)years.The anti-SSB positive group included 44 patients accounting for 31.0%of the pSS patients.The anti-SSB positive pSS patients were younger at disease onset and at visit[age at visit:(50.9±14.5)years vs.(56.5±12.4)years;age at onset:(42.2±14.8)years vs.(49.5±15.3)years,P<0.05].The patients with anti-SSB positive more frequently presented with rash(29.5%vs.14.3%,P<0.05),enlargement of parotid glands(27.3%vs.8.2%,P<0.05),renal tubular acidosis(15.9%vs.4.2%,P<0.05),immune thrombocytopenia(9.1%vs.1.0%,P<0.05),rheumatoid factor(RF)positive(85.0%vs.49.4%,P<0.05),higher RF and antinuclear antibody(ANA)titers(median:89.8 IU/mL vs.20.5 IU/mL;median:320 vs.160,P<0.05),anti-Sj gren’s syndrome type A(SSA)antibody positive(97.7%vs.64.3%,P<0.05),elevation ofγglobulin(71.4%vs.38.5%,P<0.05),higher levels of IgG(median:21.0 g/L vs.15.6 g/L,P<0.05),higher proportions of CD3^(-)CD19^(+)cells[(21.0±11.9)%vs.(13.7±9.6)%,P<0.05]and lower proportions of CD3^(+)cells[(67.2±14.4)%vs.(76.6%±13.1)%,P<0.05]than those negative.However,the anti-SSB positive group was less likely to show anti-mitochondrial antibodies(AMA)-M2 positivity(10.5%vs.35.6%,P<0.05).Glucocorticoids(90.9%vs.73.5%,P<0.05)and immunosuppressants(54.5%vs.36.7%,P<0.05)were more frequently used in anti-SSB positive pSS patients than those negative.Conclusion:The anti-SSB positive pSS patients were younger at disease onset while more frequently presenting with various symptoms,higher levels of other antibodies and activation of B cells than those negative.Glucocorticoids and immunosuppressants were more frequently used,indicating that anti-SSB positive group presented with a more severe clinal phenotype.