Sputum autoantibodies in patients with severe eosinophilic asthma

Manali Mukherjee, David C. Bulir, Katherine Radford, Melanie Kjarsgaard, Chynna Margaret Huang, Elizabeth A. Jacobsen, Sergei I. Ochkur, Ana Catuneanu, Hanah Lamothe-Kipnes, James Mahony, James J. Lee, Paige Lacy, Parameswaran K. Nair

Research output: Contribution to journalArticlepeer-review

39 Scopus citations


Background: The persistence of eosinophils in sputum despite high doses of corticosteroids indicates disease severity in asthmatic patients. Chronic inflamed airways can lose tolerance over time to immunogenic entities released on frequent eosinophil degranulation, which further contributes to disease severity and necessitates an increase in maintenance corticosteroids. Objectives: We sought to investigate the possibility of a polyclonal autoimmune event in the airways of asthmatic patients and to identify associated clinical and molecular characteristics. Methods: The presence of autoantibodies against eosinophil peroxidase (EPX) and anti-nuclear antibodies was investigated in patients with eosinophilic asthma maintained on high-dose corticosteroids, prednisone, or both. The ability of sputum immunoglobulins to induce eosinophil degranulation in vitro was assessed. In addition, the associated inflammatory microenvironment in patients with detectable autoantibodies was examined. Results: We report a “polyclonal” autoimmune event occurring in the airways of prednisone-dependent asthmatic patients with increased eosinophil activity, recurrent pulmonary infections, or both, as evident by the concomitant presence of sputum anti-EPX and anti-nuclear antibodies of the IgG subtype. Extensive cytokine profiling of sputum revealed a TH2-dominated microenvironment (eotaxin-2, IL-5, IL-18, and IL-13) and increased signalling molecules that support the formation of ectopic lymphoid structures (B-cell activating factor and B cell–attracting chemokine 1). Immunoprecipitated sputum immunoglobulins from patients with increased autoantibody levels triggered eosinophil degranulation in vitro, with release of extensive histone-rich extracellular traps, an event unsuppressed by dexamethasone and possibly contributing to the steroid-unresponsive nature of these eosinophilic patients. Conclusion: This study identifies an autoimmune endotype of severe asthma that can be identified by the presence of sputum autoantibodies against EPX and autologous cellular components.

Original languageEnglish (US)
Pages (from-to)1269-1279
Number of pages11
JournalJournal of Allergy and Clinical Immunology
Issue number4
StatePublished - Apr 2018


  • Severe asthma
  • anti-nuclear antibodies
  • autoantibodies
  • autoimmunity
  • eosinophil degranulation
  • eosinophil peroxidase
  • eosinophilia
  • sputum

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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