Asthma patients with airway autoimmunity have an altered composition of immune cells in the airway wall

<bold>Background:</bold> Airway autoantibodies reactive towards macrophages (MΦ) characterize some asthma patients. These individuals exhibit a distinct immunological response compared to those without airway autoimmunity. The origin of these autoantibodies against MΦ (α-MARCO) in asthma is unclear, but similar to findings in conditions such as Sjögren’s syndrome with pulmonary involvement, local production may occur in tertiary lymphoid structures, which are primarily composed of B cells. <bold>Aim:</bold> To investigate whether asthma patients showing signs of airway autoimmunity towards MΦ have an increased presence of B cells or other major immune cells in the airway wall compared to patients lacking such autoimmunity. <bold>Methods:</bold> Cryobiopsies from mild, steroid-naïve asthma patients with (n=12) and without (n=31) elevated α-MARCO were analyzed using chromogenic immunohistochemistry to quantify immune cells including neutrophils, eosinophils, CD20⁺ B cells, CD138⁺ plasma cells, and tryptase⁺ or chymase⁺ mast cells. α-MARCO in sputum was measured via ELISA. <bold>Results:</bold> Asthma patients with airway autoimmunity towards MΦ had a higher degree of airway hyperresponsiveness to mannitol (p=0.0057) but were clinically similar in other aspects. Patients with elevated α-MARCO had a higher number of CD20⁺ B cells in the tissue (p=0.027). Additionally, autoimmunity correlated with fewer tryptase⁺ mast cells (p=0.007) and a trend towards fewer neutrophils (p=0.067). <bold>Conclusions:</bold> Airway autoimmunity in asthma correlates with a buildup of tissue-resident B cells. These cells have the potential to differentiate into plasma cells, possibly acting as a local source for autoantibodies in asthma.