风湿免疫病相关冷球蛋白血症33例临床及免疫学特征分析

Clinical and laboratory features of rheumatic autoimmune disease associated cryoglobulinaemia

目的研究自身免疫病相关冷球蛋白血症患者的临床及实验室特征。方法回顾性分析2010年4月至2014年5月问于北京大学人民医院行冷球蛋白检测阳性的33例自身免疫病患者的临床及实验室资料。采用t检验，Mann-Whitney U检验，Fisher精确检验或，检验。结果33例合并冷球蛋白血症患者年龄12-75岁，平均（47±17）岁，其中女性26例，男性7例，诊断依次为SLE、SS、PM／DM、RA、SSc、ANCA相关性血管炎、抗磷脂综合征、PBC。SLE及SS合并冷球蛋白血症者占总例数的85％（28／33）。SLE患者出现冷球蛋白阳性的时间为2．0（1．0，12．0）年，冷球蛋白阳性患者比阴性患者肾脏受累（71％与40％，x2=15．372，P=0．004）、抗RNP抗体（56％与20％，x2=7．405，P=0．007）、心磷脂抗体（53％与8％，x2=12．356，P〈0．01）更为常见。SS患者出现冷球蛋白血症的时间为11．0（4．0，18．0）年，冷球蛋A阳性患者的RF[1170．00（230．00，2800．00）U/ml，u=0．002，P=0．001]、IgM水平[3．54（1.83，4．34）g/L，U=0．016，P=0．014]明显高于冷球蛋白阴性者[57．80（20．00，230．50）U／ml，1．17（0．81，2．26）g/L]，补体C3[0．58（0．33,0．68）g/L，U=0．004，P=0．003]、补体C4[0．06（0．03，0．12）g／L，U=0．017，P=0．016]水平显著低于冷球蛋白阴性患者0．81（0．67，0．98）g／L，0．16（0．12，0．22）g/L。结论自身免疫病合并冷球蛋白血症以SLE和SS最多。心磷脂抗体、抗RNP抗体等自身抗体，与合并冷球蛋白血症的发生呈正相关。合并冷球蛋白血症的SLE患者肾脏受累更为常见。

Objective To investigate the clinical and laboratory features of autoimmune disease （AID） associated eryoglobulinaemia. Methods From April 2010 to May 2014, thirty threc patients with AID in Peking University People＇s Hospital were tested positive for cryoglobulin. Their clinical and laboratory features were analyzed retrospectively. T test, Mann-Whitney U test, Chi-squaretest and Fisber＇s exact test were used for statistical analysis. Results Among the 33 patients, 26 were female, 7 were male, the average age was （47±17） years old （range 12-75 years old）. The spectrum of autoimmune diseases included, in order, systemic lupus erythematosus （SLE）, Sjogren＇s syndrome （SS）, multiple myositis/dermatomyositis, rheumatoid arthritis （RA）, systemic sclerosis （SSc）, anti-neutrophil cytoplasmic antibodies （ANCA）-associated vasculitis, antiphospholipid syndrome and primary biliary cirrhosis. SLE and SS accounted for 84.8% （28/33） in tpatients with cryoglobulinaemia. In patients withSLE, cryoglobulinaemia occurred at 2.0 （1.0-12.0） years after disease onset, and cryoglobulinpositive patients had more frequent renal involvement （71% vs 40%, P=0.004）, positive anti- RNP （56% vs21%, P=0.007） and ACL （53% vs 8%, P=0.000）. However, among patients with SS, cryoglobulinaemia occurred at 11.0 （4.0-18.0） years after disease onset, and cryoglobulin positive patients had higher rheumatoid factors （RF） [1 170（230.00, 2 800.00） U/ml vs 57.80（20.00, 230.50） U/ml, U=-0.002, P=0.001], IgM [3.54（1.83, 4.34） g/L vs 1.17（0.81, 2.26） g/L, U=0.016, P=0.014] and lower complement C3 [0.58（0.33, 0.68） g/L vs 0.81 （0.67, 0.98 g/L）, U=0.004, P=0.003] and C4 [0.06 （0.03, 0.12） g/L vs 0.16 （0.12, 0.22）, U=0.017, P=0.016]. Conclusion Autoimmune disease complicated with cryoglo-bulinaemia is not uncommon in clinical practice, in which SLE and SS account for the leading two causes. Patients with positive anti-RNP and/ or ACL are positively associated with cryoglobuiinaemia, renal involvement of SLE is increased by the presence of cryoglobulin.