CD6-ALCAM Pathway is Elevated in Patients with Severe Asthma

<b>Rationale:</b> CD6 is a receptor on T-cells and certain innate lymphoid cells that binds activated leukocyte cell adhesion molecule (ALCAM) on antigen presenting cells and endothelial and epithelial tissues. The CD6-ALCAM pathway is implicated in both Th2 and Th1/Th17 responses, demonstrating effects in multiple disease models including allergic asthma. Thus, we examined the CD6-ALCAM axis as a potential target for severe asthma. <b>Methods:</b> To examine CD6 expression, we analyzed a public RNASeq dataset from BAL cells of non-asthma, moderate asthma and severe asthma patients from multi-center observational studies BOBCAT and MAST. To examine ALCAM levels, sputum was collected from 22 characterized asthmatics on inhaled corticosteroids. Patients were categorized by &gt;3% or &lt;3% sputum eosinophils (sp-Eos; n=11/group) and ALCAM levels measured by ELISA. <b>Results:</b> Patients with severe asthma had significantly increased expression of CD6 with concomitant increases in T cell markers and cytokines, including <i>CD3E, CD4, CD8A, IL4, IL5, IL13, IL17F</i> and <i>IFNG</i>, compared to moderate and non-asthma patients. Analysis of sputum ALCAM levels revealed significantly higher concentrations in eosinophilic vs non-eosinophilic patients (3.8±3 vs. 1.2±1.3ng/mL; <i>p=0.04</i>). When non-eosinophilic patients were categorized by neutrophilic (n=5) or paucigranulocytic (n=6), ALCAM levels were significantly higher in eosinophilic vs. paucigranulocytic patients (0.6±0.9 ng/mL; <i>p=0.03</i>). <b>Conclusions:</b> The data indicate that the CD6-ALCAM pathway is elevated in severe asthmatics and may be a viable target in the treatment of severe, uncontrolled asthma. The ability to detect ALCAM in sputum may provide a non-invasive approach to further examine this pathway.