在接受贝利尤单抗治疗之前，免疫复合物中抗 dsDNA 抗体水平的升高与系统性红斑狼疮患者的临床应答相关。
Increased levels of anti-dsDNA antibodies in immune complexes before treatment with belimumab associate with clinical response in patients with systemic lupus erythematosus.
机构信息
Department of Immunology, Genetics and Pathology, Uppsala University, Rudbeck Laboratory, SE-75185, Uppsala, Sweden.
Rheumatology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
出版信息
Arthritis Res Ther. 2019 Nov 29;21(1):259. doi: 10.1186/s13075-019-2056-y.
INTRODUCTION
Immune complexes are of importance in systemic lupus erythematosus pathogenesis, and autoantibodies are believed to participate in immune complex formation. Quantification of autoantibody levels in circulating IC might be of prognostic value.
METHODS
A C1q-binding-eluting technique was applied to purify immune complexes from 55 belimumab-treated systemic lupus erythematosus patients during a 24-month follow-up. Autoantibodies in serum and in solubilized immune complexes were quantified using addressable laser bead immunoassay. We investigated whether levels of autoantibodies in immune complexes associate with disease activity and response to belimumab treatment.
RESULTS
High baseline anti-double-stranded DNA and anti-histone levels in immune complexes associated with attainment of zero scores in clinical systemic lupus erythematosus disease activity index 2000 during the 24-month follow-up (p = 0.003 and p = 0.048, respectively). Low complement levels associated with high serum anti-double-stranded DNA and anti-ribosomal P levels (p = 0.003 and p = 0.008, respectively) and high anti-double-stranded DNA (p = 0.002) but not anti-ribosomal P levels in immune complexes. Anti-SSA/SSB serum levels were lower in patients attaining lupus low disease activity state at month 6; these associations were stronger for corresponding immune complex levels. Serum levels of most autoantibodies had declined at month 3, whereas autoantibody levels in immune complexes, except for anti-double-stranded DNA, showed a more gradual decline over 1-2 years. Serum anti-double-stranded DNA levels decreased in all patients irrespective of systemic lupus erythematosus disease activity index 2000=0 attainment, whereas immune complex levels decreased only in achievers.
CONCLUSION
Immune complex levels of autoantibodies against double-stranded DNA and the SSA/SSB complex show more specific associations with treatment outcome compared with serum levels in belimumab-treated systemic lupus erythematosus patients. Characterization of autoantibody content in circulating immune complexes could prove useful in treatment evaluation in systemic lupus erythematosus and other immune complex-associated diseases.
简介
免疫复合物在系统性红斑狼疮发病机制中具有重要意义，并且抗体被认为参与免疫复合物的形成。循环免疫复合物中抗体水平的定量可能具有预后价值。
方法
应用 C1q 结合洗脱技术从 55 例接受贝利单抗治疗的系统性红斑狼疮患者中在 24 个月的随访期间纯化免疫复合物。使用可寻址激光珠免疫测定法定量血清和可溶性免疫复合物中的自身抗体。我们研究了免疫复合物中自身抗体的水平是否与疾病活动度和对贝利单抗治疗的反应相关。
结果
基线时免疫复合物中抗双链 DNA 和抗组蛋白抗体水平较高与 24 个月随访期间达到临床系统性红斑狼疮疾病活动指数 2000 评分 0 分相关（p=0.003 和 p=0.048）。低补体水平与血清中抗双链 DNA 和抗核糖体 P 水平较高相关（p=0.003 和 p=0.008）以及免疫复合物中抗双链 DNA 水平较高相关（p=0.002），但与抗核糖体 P 水平无关。在第 6 个月达到狼疮低疾病活动状态的患者中，血清中抗 SSA/SSB 水平较低；这些关联在相应的免疫复合物水平上更强。大多数自身抗体的血清水平在第 3 个月下降，而除了抗双链 DNA 以外，免疫复合物中的抗体水平在 1-2 年内呈更缓慢的下降。所有患者的血清抗双链 DNA 水平均下降，无论是否达到系统性红斑狼疮疾病活动指数 2000=0，而免疫复合物水平仅在达到者中下降。
结论
与接受贝利单抗治疗的系统性红斑狼疮患者的血清水平相比，针对双链 DNA 和 SSA/SSB 复合物的自身抗体的免疫复合物水平与治疗结果具有更特异的关联。循环免疫复合物中自身抗体含量的特征可能在系统性红斑狼疮和其他免疫复合物相关疾病的治疗评估中证明有用。
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