Airway autoimmunity has become recognized as a feature of severe exacerbating asthma. Asthma patients have an aggravated immune response to virus that may contribute to development of airway autoimmunity, which in turn may further increase the inflammatory response to virus. The association between airway autoimmunity and the airway epithelial response to virus has not been previously described.

The aim was to examine if asthma patients with airway autoantibodies towards macrophages (M?) have an altered bronchial epithelial immune response to virus, compared to patients without airway autoimmunity.

Protein and mRNA expression of proinflammatory and antiviral cytokines from bronchial epithelial cells after stimulation with poly(I:C) was examined using ELISA and RT-qPCR in 34 asthma patients with (n=7) and without (n=27) autoantibodies reactive to M? (?-MARCO). ?-MARCO was measured in sputum by ELISA.

Clinically, patients with airway autoimmunity towards M? were similar to patients without, but tended to be younger (p=0.08). Patients with ?-MARCO had higher induction of IL13 in response to poly(I:C) compared to patients without (p=0.033). Furthermore, autoimmunity towards M? was associated with higher induction of IL1? (p=0.027), and a tendency towards more induction of IL6 (p=0.081) and TNF? (p=0.088). On a gene level, patients with ?-MARCO had increased IL8 mRNA expression, compared to the patients without (p=0.005).

Airway autoimmunity in asthma is associated with an aggravated epithelial T2 inflammatory response to virus, as well as a broader proinflammatory response, thus linking airway autoimmunity to immune hyperresponsiveness in asthma.