title: Involvement of NLRP3 inflammasome in rituximab-induced interstitial lung disease: a case report.
abstract: OBJECTIVE
  Rituximab 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.
  
  
  METHODS
  A 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 5 days 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-1β and IL-18 in the serum were declined during the therapy.
  
  
  CONCLUSIONS
  This 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.
authors.affiliation: Department of Respiratory Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: H
authors.initials: H
authors.lastname: Kong
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: X
authors.initials: X
authors.lastname: Zeng
authors.forename: Q
authors.initials: Q
authors.lastname: Zhu
authors.forename: W
authors.initials: W
authors.lastname: Xie
authors.forename: S
authors.initials: S
authors.lastname: Dai
mesh_terms: D000328:Adult; D058846:Antibodies, Monoclonal, Murine-Derived / Q000009:adverse effects* / Q000627:therapeutic use; D002352:Carrier Proteins / Q000378:metabolism*; D016207:Cytokines / Q000097:blood; D004417:Dyspnea / Q000139:chemically induced / Q000209:etiology; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D007155:Immunologic Factors / Q000009:adverse effects / Q000627:therapeutic use; D058847:Inflammasomes / Q000378:metabolism*; D017563:Lung Diseases, Interstitial / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000188:drug therapy; D000069283:Rituximab
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D002352:Carrier Proteins; D016207:Cytokines; D005938:Glucocorticoids; D007155:Immunologic Factors; D058847:Inflammasomes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D000069283:Rituximab
keywords: inflammasome; interstitial lung disease; rituximab