Involvement of NLRP3 inflammasome in rituximab-induced interstitial lung disease: a case report
Involvement of NLRP3 inflammasome in rituximab-induced interstitial lung disease: a case report
复制标题
DOI：
10.1111/jcpt.12198
复制
发表时间：
2014-12-01
影响因子：
2
通讯作者：
Dai, S.
中科院分区：
文献类型：
--
作者：
Kong, H.;Wang, Y.;Dai, S.
利妥昔单抗（Rituximab）是一种嵌合的抗CD 20 IgG 1单克隆抗体，用于治疗各种形式的淋巴瘤和血液系统自身免疫性疾病。间质性肺病是一种罕见但致命的利妥昔单抗肺毒性。Nod-like receptor pyrin domain-containing protein 3（NLRP 3）炎性体是一种分子平台，在细胞危险迹象时被激活以触发促炎细胞因子的成熟。我们报告第一例利妥昔单抗诱导的间质性肺病（R-ILD）与NLRP 3炎性小体激活在lung.Case summaryA 30岁男性患者诊断为特发性血小板减少性紫癜（ITP）治疗与利妥昔单抗在一个月内的四个周期。利妥昔单抗末次给药后3周，患者发生进行性呼吸困难伴呼吸衰竭，诊断为R-ILD。患者对类固醇治疗反应良好，治疗后5天进行肺活检。肺组织免疫组织病理学研究显示炎性小体成分NLRP 3、含有caspase募集结构域（ASC）的凋亡相关斑点样蛋白和caspase-1在肺组织中高表达，并伴有CD 19阳性细胞的大量浸润。结论：本研究首次证实了NLRP 3炎性小体在利妥昔单抗肺毒性中的作用。通过类固醇治疗抑制肺中NLRP 3炎性体的活化可以逆转R-ILD并阻断随后的肺纤维化。这一结果为研究R-ILD的发病机制提供了新的视角，也为R-ILD的治疗提供了新的靶点。
What is known and objectiveRituximab is a chimeric anti-CD20 IgG1 monoclonal antibody for the treatment of various forms of lymphoma and haematological autoimmune diseases. Interstitial lung disease is a rare but lethal pulmonary toxicity of rituximab. Nod-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome is a molecular platform activated upon signs of cellular danger' to trigger the maturation of pro-inflammatory cytokines. We report the first case of rituximab-induced interstitial lung disease (R-ILD) with NLRP3 inflammasome activation in the lung.Case summaryA 30-year-old male patient diagnosed with idiopathic thrombocytopenic purpura (ITP) was treated with four cycles of rituximab in one month. Three weeks after last rituximab administration, he developed progressive dyspnoea associated with respiratory failure, which was diagnosed as R-ILD. The patient showed a good response to steroid treatment, and lung biopsy was performed 5days after the treatment. Immunohistopathological studies of lung specimens showed high expressions of inflammasome components NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and caspase-1 in lung interstitium with a heavy infiltration of CD19-positive cells. The levels of inflammasome-related cytokines IL-1 and IL-18 in the serum were declined during the therapy.What is new and conclusionsThis is the first report confirmed the role of NLRP3 inflammasome in pulmonary toxicity of rituximab. Inhibited activation of NLRP3 inflammasome in lung by steroid treatment could reverse R-ILD and block subsequent lung fibrosis. This result could open a new sight into the pathogenesis and provide a new target for the treatment of R-ILD.