Pretreatment circulating MAIT cells, neutrophils, and periostin predicted the real-world response after 1-year mepolizumab treatment in asthmatics

  • Sasano Hitoshi
    Department of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine
  • Harada Norihiro
    Department of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine Research Institute for Diseases of Old Ages, Juntendo University Faculty of Medicine and Graduate School of Medicine Atopy (Allergy) Research Center, Juntendo University Graduate School of Medicine
  • Harada Sonoko
    Department of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine Atopy (Allergy) Research Center, Juntendo University Graduate School of Medicine
  • Takeshige Tomohito
    Department of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine
  • Sandhu Yuuki
    Department of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine
  • Tanabe Yuki
    Department of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine
  • Ishimori Ayako
    Department of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine
  • Matsuno Kei
    Department of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine
  • Nagaoka Tetsutaro
    Department of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine
  • Ito Jun
    Department of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine
  • Chiba Asako
    Department of Immunology, Juntendo University Graduate School of Medicine
  • Akiba Hisaya
    Department of Immunology, Juntendo University Graduate School of Medicine
  • Atsuta Ryo
    Department of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine
  • Izuhara Kenji
    Division of Medical Biochemistry, Department of Biomolecular Sciences, Saga Medical School
  • Miyake Sachiko
    Department of Immunology, Juntendo University Graduate School of Medicine
  • Takahashi Kazuhisa
    Department of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine Research Institute for Diseases of Old Ages, Juntendo University Faculty of Medicine and Graduate School of Medicine

抄録

<p>Background: Mepolizumab treatment improves symptom control and quality of life and reduces exacerbations in patients with severe eosinophilic asthma. However, biomarkers that predict therapeutic effectiveness must be determined for use in precision medicine. Herein, we elucidated the dynamics of various parameters before and after treatment as well as patient characteristics predictive of clinical responsiveness to mepolizumab after 1-year treatment.</p><p>Methods: Twenty-seven patients with severe asthma were treated with mepolizumab for one year. Asthma control test scores, pulmonary function tests, fractional exhaled nitric oxide levels, and blood samples were evaluated. Additionally, we explored the role of CD69-positive mucosal-associated invariant T (MAIT) cells as a candidate biomarker for predicting treatment effectiveness by evaluating an OVA-induced asthma murine model using MR1 knockout mice, where MAIT cells were absent.</p><p>Results: The frequencies of CD69-positive group 1 innate lymphoid cells, group 3 innate lymphoid cells, natural killer cells, and MAIT cells decreased after mepolizumab treatment. The frequency of CD69-positive MAIT cells and neutrophils was lower and serum periostin levels were higher in responders than in non-responders. In the OVA-induced asthma murine model, CD69-positive MAIT cell count in the whole mouse lung was significantly higher than that in the control mice. Moreover, OVA-induced eosinophilic airway inflammation was exacerbated in the MAIT cell-deficient MR1 knockout mice.</p><p>Conclusions: This study shows that circulating CD69-positive MAIT cells, neutrophils, and serum periostin might predict the real-world response after 1-year mepolizumab treatment. Furthermore, MAIT cells potentially have a protective role against type 2 airway inflammation.</p>

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