Bu Xiangmao, Zhang Tenglong, Wang Chunhong, Ren Tao, Wen Zhenke
Department of Clinical Laboratory, Qingdao Women & Children Hospital, Qingdao, 266034, Shandong, China.
Department of Oncology, Qingdao Municipal Hospital, Qingdao, 266071, Shandong, China.
J Transl Med. 2015 Dec 16;13:381. doi: 10.1186/s12967-015-0745-0.
Autoimmune hemolytic anemia (AIHA), a life-threatening anemia with rapid onset, is caused by autoantibody directed to self red blood cells (RBCs). Currently, mechanisms underlying AIHA pathogenesis are largely undefined. Here we explored the correlation of IL-33 with AIHA disease activity and evaluated IL-33 based therapeutics in AIHA treatment.
Thirty patients diagnosed with AIHA of warm-type autoantibodies without treatment were enrolled and followed up for 6 months. Levels of cytokines including IL-33, IL-4, IL-6 and IL-13 was determined with ELISA. AIHA disease activity was presented by levels of reticulocyte count, hemoglobin and lactate dehydrogenase. Serum RBC-bound IgG autoantibody was detected using anti-IgG antibody with flow cytometry. To evaluate the effect of IL-33 blockade on AIHA development, groups of B6 mice were immunized with rat RBCs plus recombinant IL-33 protein or IL-33 neutralizing antibody respectively and detected for levels of anti-RBC antibody, frequency of reticulocytes and destruction of transfused syngeneic mouse RBCs.
Serum level of IL-33 was higher in AIHA patients compared with healthy individuals. Of interest, serum IL-33 was positively correlated with AIHA disease activity and sensitive to their changes in AIHA patients under clinical management. Mechanistically, IL-33 could promote the production of anti-RBC autoantibody. Serum IL-33 was closely associated with serum anti-RBC autoantibody and sensitive to their changes in AIHA patients. Accordingly, blockade of IL-33 interfered with AIHA incidence and ameliorated disease activity. Vice vasa, enforced IL-33 promoted AIHA incidence and disease activity.
IL-33 was a potential biomarker for monitoring disease activity and therapeutic response in AIHA patients. Targeting IL-33 was a promising strategy for controlling autoantibody production in AIHA patients.
自身免疫性溶血性贫血（AIHA）是一种起病迅速、危及生命的贫血症，由针对自身红细胞（RBC）的自身抗体引起。目前，AIHA发病机制的基础在很大程度上尚不清楚。在此，我们探讨了白细胞介素-33（IL-33）与AIHA疾病活动的相关性，并评估了基于IL-33的疗法在AIHA治疗中的效果。
纳入30例未经治疗的暖型自身抗体AIHA患者，并随访6个月。采用酶联免疫吸附测定法（ELISA）测定包括IL-33、IL-4、IL-6和IL-13在内的细胞因子水平。AIHA疾病活动通过网织红细胞计数、血红蛋白和乳酸脱氢酶水平来体现。使用抗IgG抗体通过流式细胞术检测血清红细胞结合IgG自身抗体。为评估IL-33阻断对AIHA发展的影响，将B6小鼠分组，分别用大鼠红细胞加重组IL-33蛋白或IL-33中和抗体进行免疫，并检测抗红细胞抗体水平、网织红细胞频率以及输注的同基因小鼠红细胞的破坏情况。
与健康个体相比，AIHA患者的血清IL-33水平更高。有趣的是，血清IL-33与AIHA疾病活动呈正相关，并且在临床管理下对AIHA患者的变化敏感。从机制上讲，IL-33可促进抗红细胞自身抗体的产生。血清IL-33与血清抗红细胞自身抗体密切相关，并且对AIHA患者的变化敏感。因此，阻断IL-33可干扰AIHA的发生并改善疾病活动。反之，增强IL-33会促进AIHA的发生和疾病活动。
IL-33是监测AIHA患者疾病活动和治疗反应的潜在生物标志物。靶向IL-33是控制AIHA患者自身抗体产生的一种有前景的策略。
