Group 2 Innate Lymphoid Cells Directly Induce B Cell Activation in Humans

Kasjanski, Richard; Kato, Atsushi; Poposki, Julie A.; Bochner, Bruce S.; Cao, Yun; Norton, James E.; Suh, Lydia; Carter, Roderick G.; Kern, Robert C.; Smith, Stephanie Shintani; Conley, David B.; Peters, Anju T.; Grammer, Leslie C.; Stevens, Whitney W.; Harris, Kathleen E.; Tan, Bruce K.; Schleimer, Robert P.; Hulse, Kathryn E.

doi:10.1016/j.jaci.2015.12.003

Cited by 1 publication

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“…Incidentally, there was also an increase documented for sputum B-cell activity (B-cell activating factor (BAFF) levels: pre-Mepolizumab, Feb-13—19.2 pg/mL to post-Mepolizumab, Oct-14: 228 pg/mL). We speculate that increase in activated ILC2s contributed to the local B-cell activity since the former has recently been reported to activate and promote survival of B-cells in vitro [14]. The concurrent increase in eosinophils and autoantibodies would allow spontaneous IgG-mediated eosinophil degranulation in the airways, an event that is known to be steroid-unresponsive [15].…”

Section: Discussion and Molecular Insightsmentioning

confidence: 99%

Airway autoimmune responses in severe eosinophilic asthma following low-dose Mepolizumab therapy

Mukherjee

Lim

Thomas

et al. 2017

Allergy Asthma Clin Immunol

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BackgroundAnti-interleukin (IL)-5 monoclonal antibodies as an eosinophil-depleting strategy is well established, with Mepolizumab being the first biologic approved as an adjunct treatment for severe eosinophilic asthma.Case presentationA 62-year old woman diagnosed with severe eosinophilic asthma showed poor response to Mepolizumab therapy (100 mg subcutaneous dose/monthly) and subsequent worsening of symptoms. The treatment response to Mepolizumab was monitored using both blood and sputum eosinophil counts. The latter was superior in assessing deterioration in symptoms, suggesting that normal blood eosinophil count may not always indicate amelioration or adequate control of the ongoing eosinophil-driven disease process. This perplexing situation of persistent airway eosinophilia and increased steroid insensitivity despite an anti-eosinophil therapy can be explained if the administered dose of the mAb was inadequate in comparison to the target antigen. The resultant immune complexes could act as ‘cytokine depots’, protecting the potency of the ‘bound’ IL-5, thereby sustaining the eosinophilic inflammation within the target tissue. Molecular analysis of the sputum indicated the development of a polyclonal autoimmune response as well as an increase in group 2 innate lymphoid cells, two novel observations in severe eosinophilic asthma, which were associated with indices of disease severity and progression. This case highlights the possibility of a previously unrecognised autoimmune-mediated worsening of asthma perhaps triggered by immune complexes formed due to inadequate dosing of administered monoclonal antibodies in the target tissue.ConclusionsWhile anti-IL5 mAb therapy is an exciting novel option to treat patients with severe asthma, there is the rare possibility of worsening of asthma as observed in this case study, due to local autoimmune mechanisms precipitated by potential inadequate airway levels of the monoclonal antibody.Electronic supplementary materialThe online version of this article (doi:10.1186/s13223-016-0174-5) contains supplementary material, which is available to authorized users.

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Section: Discussion and Molecular Insightsmentioning

confidence: 99%