干燥综合征合并单克隆免疫球蛋白病临床特征治疗及预后分析

Clinical features, treatment and follow-ups of Sjogren＇s syndrome-associated monoclonal gammopathy

目的探讨SS合并单克隆免疫球蛋白病（SS-MG）患者的临床和免疫学特征、治疗及预后分析。方法回顾性分析北京大学人民医院2010年1月至2017年1月确诊SS-MG的18例患者，以性别、年龄、入院时间相匹配的36例未合并MG的SS患者为对照组进行病例对照研究。计数资料进行χ2检验、连续校正的χ2检验或Fisher确切概率法；符合正态分布的计量资料采用t检验，非正态分布的计量资料用Mann-Whitney U检验。结果SS-MG组血清总蛋白[（78±11）g/L，（71±10）g/L，t=-2.382，P=0.021]、ESR[52.5（45.3）mm/1 h，33.0（42.5）mm/1 h，Z=-2.179，P=0.029]、尿N-乙酰-β-D-氨基葡萄糖苷酶（NAG）阳性[75%（9/12），28%（7/25），χ2=7.298，P=0.007]、低免疫球蛋白血症[33%（6/18），3%（1/36），χ2=7.407，P=0.006]和血栓事件发生率[17%（3/18），0（0/36），P=0.033]较对照组升高，既往糖皮质激素使用率[22%（4/18），64%（23/36），χ2=8.333，P=0.004]低于对照组，差异均有统计学意义。合并MG的pSS患者pSS疾病活动度指数（ESSDAI）[26.0（25.0），12.0（9.0），Z=-2.724，P=0.006]和临床疾病活动指数（ClinESSDAI）[24.0（25.0），10.5（10.0），Z=-2.523，P=0.011]评分显著高于对照组pSS患者。SS-MG患者最终诊断多发性骨髓瘤2例、非霍奇金淋巴瘤合并浆细胞肾小管间质浸润所致肾功能不全1例、意义未明的单克隆免疫球蛋白血症（MGUS）15例。10例患者接受随访，其中2例MGUS患者存在M蛋白水平增高、遗传学进展及肾脏受累。结论SS患者可在病程中合并MG，以MGUS最为常见，也可存在恶性转化。在血清总蛋白升高、ESR增快、合并低免疫球蛋白血症和肾小管间质受累，及存在不明原因血栓事件的SS患者，尤其是高疾病活动度的患者中，需高度警惕，以早期诊断、严密监测，以把握正确的治疗时机。

Objective To investigate the clinical characteristics, immunological features, treatment and follow-ups of Sj？gren＇s syndrome-associated monoclonal gammopathy （SS-MG）. Methods A retro-spective, case-control study was conducted for 18 cases diagnosed with SS-MG and 36 age- and sex-matched non-MG- SS patients from Janurary 2010 to Janurary 2017 in Peking University People＇s Hospital. The clinical and laboratory features, treatment and follow-ups were recorded and compared. Comparisons between groups were made using t test for normally distributed numerical data, Mann-Whitney U test for non-normally distributed numerical data, and Pearson Chi-square, continuity correction or Fisher＇s exact tests for categorical data.Results SS patients, when complicated with MG, had significantly increased level of TP [（78±11） g/L, （71±10） g/L, t=-2.382, P=0.021] and erythrocyte sedimentation rate （ESR） [52.5（45.3） mm/1 h, 33.0（42.5） mm/1 h, Z=-2.179, P=0.029], higher prevalence of urine NAG positivity [75%（9/12）, 28%（7/25）, χ2=7.298, P=0.007], hypoglobulinemia [33%（6/18）, 3（1/36）, χ2=7.407, P=0.006] and thrombotic events [17%（3/18）, 0%（0/36）, P=0.033], and less previous exposure to glucocorticoid [22%（4/18）, 64%（23/36）, χ2=8.333, P=0.004], compared to the control group. Primary SS patients complicated with MG had significantly higher ESSDAI[26.0（25.0）,12.0（9.0）, Z=-2.724, P=0.006] and Clin EULAR Sj？gren＇s syndrome disease activity index （ESSDAI） [24.0（25.0）, 10.5（10.0）, Z=-2.523, P=0.011]. Among the 18 patients, 2 were diagnosed with multiple myeloma, 1 was diagnosed with non-Hodgkin lymphoma, and the left were diagnosed as MG of undetermined significance （MGUS）. Ten patients were followed up, among whom 2 patients with MGUS experienced increased levels of M protein, newly developed genetic abnormalities, and renal involvement.Conclusion SS patients may be complicated with MG. MGUS is the most common form. However, malignant hematologic disorders are revealed as well. In SS patients with high serum TP and ESR, hypoglobulinemia, tubulointerstitial kidney involvement and unexplained thrombotic events, especially in those with high disease activity, so MG should be an alert for further work-ups, monitoring and treatment.