Airway autoimmunity and response to a 14-day course of oral corticosteroids in patients with severe eosinophilic asthma

<b>Background:</b> Recent studies have suggested airway autoimmunity underlying persistent eosinophilia in prednisone-dependent severe asthma. <i>In vitro</i> studies report autoantibody (aAb)-mediated eosinophilia unresponsive to corticosteroids. <b>Aim:</b> To determine the treatment (Rx) response of oral corticosteroids (OCS, prednisolone) on eosinophil suppression in autoimmune-prone asthmatic airways, without the confounder of patients already on OCS. <b>Methods:</b> We evaluated 23 eosinophilic (≥3% sputum eosinophils) patients with severe asthma (per ERS/ATS guidelines) not maintained on OCS, post 14 days of 37.5mg prednisolone. Anti-eosinophil peroxidase (EPX) IgG was measured in the sputa (ELISA) as a marker of airway autoimmunity and compared with clinical measures of eosinophilia pre- and post Rx. <b>Results:</b> Five (21.7%) patients tested positive for anti-EPX IgG. This subgroup had significantly higher blood eosinophil counts (median 0.70 x 10⁹/L (range 0.38–2.40) vs. 0.27 (0.08–0.75), p=0.0019), sputum free eosinophil granules (FEGs) (median 3.00 (range 2.00–3.00) vs. 0.00 (0.00-2.00), p&lt;0.001) and a trend towards higher sputum eosinophils (p=0.12) at baseline compared with patients with low/no anti-EPX IgG. Post Rx, reduction in blood and sputum eosinophils was comparable (p&lt;0.001 for both groups and p=0.62 and p=0.32 across groups) while anti-EPX titers were suppressed in 4/5 patients. <b>Conclusions:</b> We detected sputum aAbs in a subgroup of severe asthma patients (not on daily OCS) with blood eosinophilia and airway eosinophil activity (FEGs). Our data suggests that airway autoimmune responses in severe asthma may be curbed by a course of prednisolone with concurrent suppression of eosinophilia.