title: Plasma plasmin-α2-plasmin inhibitor complex levels may predict the effect of cyclophosphamide for systemic sclerosis-related interstitial lung disease.
abstract: OBJECTIVE
  Intravenous pulse cyclophosphamide (IVCY) is the first-line treatment for systemic sclerosis-associated interstitial lung disease (SSc-ILD). So far, there is no useful predictive marker for IVCY efficacy against SSc-ILD, although potential candidates are parameters reflecting vascular activation. Since plasma levels of plasmin-α2-plasmin inhibitor complex (PIC) serve as a potential biomarker of SSc vasculopathy, we evaluated the usefulness of plasma PIC levels as an indicator for IVCY efficacy against SSc-ILD.
  
  
  METHODS
  We measured plasma PIC levels in 23 patients with active SSc-ILD and 20 patients with stabilized SSc-ILD, and also retrospectively studied traceable data of patients with active SSc-ILD during IVCY therapy.
  
  
  RESULTS
  Plasma PIC levels were significantly elevated in patients with active SSc-ILD as compared to patients with stabilized SSc-ILD. Among patients with active SSc-ILD, baseline plasma PIC concentrations were significantly higher in patients responsive to IVCY than in those refractory to IVCY. After the entire six infusions, plasma PIC levels were significantly decreased compared with baseline in the responders, while not in the nonresponders. In the responders, plasma PIC levels were remarkably decreased after a couple of infusions. Regarding the changes of parameters by the entire infusions, Δ plasma PIC levels correlated positively with Δ serum KL-6 levels and inversely with Δ the percentage of predicted vital capacity.
  
  
  CONCLUSIONS
  The elevation of baseline plasma PIC levels and the rapid decrease in plasma PIC levels during a couple of infusions may predict the efficacy of the entire IVCY therapy against SSc-ILD.
authors.affiliation: a Department of Dermatology , University of Tokyo Graduate School of Medicine , Bunkyo-ku , Tokyo , Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Saigusa
authors.affiliation: a Department of Dermatology , University of Tokyo Graduate School of Medicine , Bunkyo-ku , Tokyo , Japan.
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Asano
authors.affiliation: a Department of Dermatology , University of Tokyo Graduate School of Medicine , Bunkyo-ku , Tokyo , Japan.
authors.forename: Kouki
authors.initials: K
authors.lastname: Nakamura
authors.affiliation: a Department of Dermatology , University of Tokyo Graduate School of Medicine , Bunkyo-ku , Tokyo , Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamashita
authors.affiliation: a Department of Dermatology , University of Tokyo Graduate School of Medicine , Bunkyo-ku , Tokyo , Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Ichimura
authors.affiliation: a Department of Dermatology , University of Tokyo Graduate School of Medicine , Bunkyo-ku , Tokyo , Japan.
authors.forename: Takehiro
authors.initials: T
authors.lastname: Takahashi
authors.affiliation: a Department of Dermatology , University of Tokyo Graduate School of Medicine , Bunkyo-ku , Tokyo , Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Toyama
authors.affiliation: a Department of Dermatology , University of Tokyo Graduate School of Medicine , Bunkyo-ku , Tokyo , Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Taniguchi
authors.affiliation: a Department of Dermatology , University of Tokyo Graduate School of Medicine , Bunkyo-ku , Tokyo , Japan.
authors.forename: Ayumi
authors.initials: A
authors.lastname: Yoshizaki
authors.affiliation: a Department of Dermatology , University of Tokyo Graduate School of Medicine , Bunkyo-ku , Tokyo , Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Miyazaki
authors.affiliation: a Department of Dermatology , University of Tokyo Graduate School of Medicine , Bunkyo-ku , Tokyo , Japan.
authors.forename: Zenshiro
authors.initials: Z
authors.lastname: Tamaki
authors.affiliation: a Department of Dermatology , University of Tokyo Graduate School of Medicine , Bunkyo-ku , Tokyo , Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Sato
mesh_terms: D018501:Antirheumatic Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D003520:Cyclophosphamide / Q000627:therapeutic use*; D005260:Female; D005341:Fibrinolysin / Q000378:metabolism*; D006801:Humans; D017563:Lung Diseases, Interstitial / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012595:Scleroderma, Systemic / Q000097:blood / Q000150:complications*; D016896:Treatment Outcome; D000979:alpha-2-Antiplasmin / Q000378:metabolism*
chemical_list: D018501:Antirheumatic Agents; D015415:Biomarkers; D000979:alpha-2-Antiplasmin; C037742:plasmin-plasmin inhibitor complex; D003520:Cyclophosphamide; D005341:Fibrinolysin
keywords: Biomarker; cyclophosphamide; interstitial lung disease; plasmin-α2-plasmin inhibitor complex; systemic sclerosis