The following is a summary of “Airway autoantibodies are determinants of asthma severity” published in the December 2022 issue of Respiratory by Salter et al.

The need for steroid treatment and persistent eosinophilia in severe asthma may be related to autoimmune reactions at the local airway level. It has been shown that auto-IgG antibodies can target granule proteins such eosinophil peroxidase (EPX), macrophage scavenger receptor with collagenous structure (MARCO), and nuclear/extranuclear antigens (ANAs). Their goal was to characterize the frequency and clinical features of airway autoreactivity in asthmatic patients and to see if the presence of this phenomenon could be anticipated by a patient’s clinical history of autoreactivity.  The relationship between anti-EPX, anti-MARCO, and ANAs and lung function metrics, blood/airway inflammation, severity indices, and exacerbations was assessed in 218 sputum samples collected prospectively from 148 individuals with asthma. 

About  107  of these patients also agreed to fill out an autoimmune checklist to record their and their families’ experiences with systemic autoimmune illness and related symptoms.  59  out of 148 patients (40%) exhibited anti-EPX IgG + antibodies, 53 out of 148 (36%) had anti-MARCO IgG+ antibodies, and 64 out of 129 (50%) had ≥2 nuclear/extranuclear auto reactivities. The composite airway autoreactivity score(CAAS) showed that 82 individuals (55%) exhibited airway auto reactivities in excess of 2 (CAAS+). The presence of CAAS+ was predicted by elevated levels of airway eosinophil degranulation (OR 15.1, 95% CI 1.1-199.4), blood leukocytes (OR 3.5, 95% CI 1.3-10.1), and blood lymphocytes (OR 0.19, 95% CI 0.04-0.84). About 3/5  of CAAS+ patients said they had an exacerbation, and this was linked to higher levels of anti-EPX and/or anti-MARCO IgG (P<0.05). 

About 30% of CAAS+ asthmatic patients experienced sicca symptoms (P=0.02), although there was no correlation between a family history or personal diagnosis of autoimmune disease and this finding. Despite suppressing eosinophils, the current anti-inflammatory treatment (inhaled/oral corticosteroids and/or adjunct anti-interleukin-5 biologics) did not reduce airway autoantibodies.  Researchers found that airway autoreactivity was present in 55% of patients with moderate-severe asthma and that this autoreactivity persisted despite anti-inflammatory medication, which in turn was related to exacerbations.