IL-13 Blockade and Airway Autoimmunity in Asthma

It has been observed that certain section of patients having severe to moderate Asthma, do not benefit from oral corticosteroids and IL-5 blocking biologics. There is increasing evidence that Airway auto immunity may be responsible for this poor response to treatment. It has been seen in earlier study done at Nair lab that these patients might benefit from Dupilumab, a biologic blocking IL-13/ IL-4. IL-13/IL-4 are the cytokines responsible for increased inflammation in these Asthmatics. The hypothesis is that blocking IL-13/IL-4 will also reduce the airway auto immunity which can be measured by comparing the auto immune markers in airway at baseline (before starting Dupilumab) and 16 weeks (after 4 months of Dupilumab treatment.

Asthma, a chronic airway disease characterized by reversible airflow, airway inflammation and hyper responsiveness. A prominent phenotype is eosinophilic asthma, with a prevalence rate of \~50% and characterised by blood eosinophils \>300 cells/μL and sputum eosinophils \>3%. Inhaled corticosteroids (ICS) have been successful for treatment of mild-to-moderate asthma. However, \~10% of eosinophilic asthmatics remain uncontrolled despite being on high dose oral corticosteroids. This small percentage contributes disproportionately to 80% of asthma healthcare costs \[8-10\]. As a steroid-sparing strategy, monoclonal antibody (mAb) therapies targeting interleukin (IL)-5 signalling have been developed that are projected to benefit this difficult-to-treat population. Yet, a subset (30-50%) of them remain symptomatic despite being on oral corticosteroids (OCS) and adjunct anti-IL-5 mAb. Anti- eosinophil peroxidase (EPX) Immunoglobulin G (IgG) levels in the airways strongly correlated with the presence of other auto antibodies, in particular the anti-nuclear antibodies (ANAs) as well as various clinical features of asthma severity. Therefore, a better understanding of the underlying pathology with subsequent identification of clinical/molecular biomarkers remains an unmet clinical need for optimal asthma management. Airway autoimmune responses in severe asthma is an important contributor to airway mucus and this can be ameliorated by blocking the IL-4/IL-13 inflammatory axis.