免疫吸附治疗合并血管病变的重症狼疮性肾炎

Therapeutic effect of immunoadsorption in severe lupus nephritis with vascular lesions

目的:探讨辅助应用葡萄球菌蛋白A(SPA)免疫吸附(IA)疗法对重症狼疮性肾炎(LN)的临床疗效和安全性。方法:13例重症LN(女11例、男2例,年龄15～44岁),肾活检病理类型为IV型(n=10)和V+IV型(n=3),其中11例伴间质血管病变(血栓性微血管病8例,非炎症坏死性血管病3例)。92.3%(12/13)患者入院时血清肌酐(SCr)升高[平均(309.4±203.3)μmol/L],其中3例需行肾脏替代治疗。采用IA联合激素和霉酚酸酯(MMF)治疗,观察IA治疗前后疾病活动指数(DAI)、肾功能和免疫学指标变化,随访疗效及不良反应。结果:(1)临床疗效:IA平均治疗4.5次(3～7次),IA结束时SLE-DAI[(18.6±4.5)分vs(11.5±1.4)分,P<0.01]和SCr[(309.4±203.3)μmol/Lvs(238.7±141.4)μmol/L,P<0.01]均显著下降,3例需肾脏替代治疗的患者中1例IA结束后即摆脱透析,1例在随访中摆脱透析;(2)免疫学指标变化:IA后ANA滴度下降;58.3%(7/12)患者抗-dsDNA抗体转阴,41.7%(5/12)抗-dsDNA抗体滴度下降。补体C3[(0.36±0.18)g/Lvs(0.48±0.11)g/L,P<0.01]和C4[(0.08±0.05)g/Lvs(0.16±0.10)g/L,P<0.05]均较治疗前明显升高。IA后CD4+淋巴细胞明显下降[(309±205)个/μlvs(191±102)个/μl,P<0.05];(3)随访结果:2例失访,其余11例随访3～18月[平均(9.8±5.0)月],8例(72.7%)SCr降至正常,其中2例完全缓解,8例部分缓解;(4)不良反应:IA期间2例出现过敏反应,2例合并感染(肺炎和细菌性痢疾各1例)。结论:IA能有效清除LN患者血清多种自身抗体,免疫抑制药物联合IA有助于提高合并血管病变重症LN的临床疗效。

Objective ：To investigate the clinical efficacy and adverse reactions of staphylococcal protein A immunoadsorption （IA） in patients with severe lupus nephritis （LN）. Methodology ：Thirteen patients, who were 11 females, 2 males, and 15 -44 years old, with severe LN including class Ⅳ （n = 10） and class Ⅴ ＋ Ⅳ （n =3） were studied. Among them, there were 11 eases （ 84. 6% ） with vascular lesions of thrombotic microangiopathy （TMA） （ n = 8 ） or noninflammatory neerotizing vasculopathy （NNV） （ n = 3 ）, 12 cases （ 92. 3 % ） with elevating serum creatinine （ SCr ） [ average （309.4 ± 203.3 ） μmol/L] , and 3 cases with renal replacement therapy. All of patients were received IA therapy accompanied with steroid and MMF. The parameters of systemic lupus erythematosus disease activity index （SLE-DAI） , renal function, and immunologic exanimation were evaluated. The efficacy and adverse reactions were observed. Results： 1 ） Clinical efficacy ： IA treated for 4.5 times （ 3 - 7 ）. SLE-DAI was decreased significantly from 18.6 ±4. 5 to 11.5 ± 1. 4 （P 〈0. 01 ）, and SCr from （309.4 ±203.3） to （238. 7 ± 141.4） μmol/L （P 〈0. 01 ） after IA. 2） Immunologic examinations ： The titers of ANA and anti-dsDNA were significantly declined after IA, while the levels of complement C3 were increased significantly from （0.36 ±0. 18） to （0.48 ±0. 11） g/L （P 〈0.01）and C4 from （0.08 ±0.05） to （0. 16 ±0. 10） g/L （P 〈 0.05 ）. The level of CD4^＋ lymphocyte was decreased markedly fom （309 ± 206） to （191±102）/μl （P 〈 0. 05 ）, after IA. 3 ） Follow up ： 11 cases followed up for 3 to 18 mon （ 9. 8±5.0 ）. The renal function were recovered in 8（72. 7% ） cases. 2 cases received complete remission, and 8 cases partial remission. 4） Adverse reactions： During IA, 2 cases had hypersensitivity, and 2 infections. Conclusion：IA could rapidly and effectively removed all kinds of autoantibodies in LN. IA accompanied with immunosuppressor is one of indications for severe LN with vascular lesions.