Soluble Major Histocompatibility Complex Class I-Related Chain B Molecules Are Increased and Correlate With Clinical Outcomes During Rhinovirus Infection in Healthy Subjects

Aurica G. Telcian, MD, PhD; Mihnea T. Zdrenghea, MD, PhD; Gaetano Caramori, MD, PhD; Vasile Laza-Stanca, MD, PhD; Simon D. Message, MD, PhD; Tatiana Kebadze, MD; Onn M. Kon, MD, PhD; Veronika Groh, PhD; Alberto Papi, MD, PhD, FCCP; Sebastian L. Johnston, MD, PhD; Patrick Mallia, MD, PhD; Luminita A. Stanciu, MD, PhD

BACKGROUND: Surface major histocompatibility complex class I-related chain (MIC) A and B molecules are increased by IL-15 and have a role in the activation of natural killer group 2 member D-positive natural killer and CD8 T cells. MICA and MICB also exist in soluble forms (sMICA and sMICB). Rhinoviruses (RVs) are the major cause of asthma exacerbations, and IL-15 levels are decreased in the airways of subjects with asthma. The role of MIC molecules in immune responses in the lung has not been studied. Here, we determine the relationship between MICA and MICB and RV infection in vitro in respiratory epithelial cells and in vivo in healthy subjects and subjects with asthma.

METHODS: Surface MICA and MICB, as well as sMICA and sMICB, in respiratory epithelial cells were measured in vitro in response to RV infection and exposure to IL-15. Levels of sMICA and sMICB in serum, sputum, and BAL were measured and correlated with blood and bronchoalveolar immune cells in healthy subjects and subjects with asthma before and during RV infection.

RESULTS: RV increased MICA and MICB in vitro in epithelial cells. Exogenous IL-15 upregulated sMICB levels in RV-infected epithelial cells. Levels of sMICB molecules in serum were increased in healthy subjects compared with subjects with stable asthma. Following RV infection, airway levels of sMIC are upregulated, and there are positive correlations between sputum MICB levels and the percentage of bronchoalveolar natural killer cells in healthy subjects but not subjects with asthma.

CONCLUSIONS: RV infection induces MIC molecules in respiratory epithelial cells in vitro and in vivo. Induction of MICB molecules is impaired in subjects with asthma, suggesting these molecules may have a role in the antiviral immune response to RV infections.

Chest. 2014;146(1):32-40. doi:10.1378/chest.13-2247