IgE and antiviral immune response in asthma

Correspondence IgE and antiviral immune response in asthma To the Editor: We read with interest the article by Kantor et al,1 in which they showed that rhinovirus-triggered asthma exacerbation was associated with higher asthma exacerbation severity and drove a higher antigen-specific IgE response. Looking specifically at mouse and dust mite sensitization, they found that the magnitude of the rise in specific IgE level was associated with the severity of the rhinovirus-triggered asthma exacerbation. On the basis of this, they concluded that interactions between rhinovirus infection and allergen-specific IgE levels may help to explain interindividual variation in disease manifestation. However, we might suggest that this association may support another possible explanation. It has been shown that humans make IgE against respiratory viruses2; in particular, we have shown that humans can make rhinovirus-specific IgE.3 It would be interesting to see if in the patients with elevated mouse-specific and dust mite–specific IgE, if they also had rhinovirus-specific IgE as a cause of the increased severity of the asthma exacerbation. Interestingly, in a strain-dependent mouse model of asthma using the rodent parainfluenza virus type 1 (Sendai virus), development of airway disease depends on antiviral IgE cross-linking FcεRI on lung dendritic cells.4 Moreover, in this model, a single exposure to a bystander allergen during the viral infection is sufficient to drive marked allergen-specific IgE production.5 These findings in the mouse model parallel findings presented by the authors in humans with rhinoviral infections. It furthers the authors’ suggestion of a possible mechanism with the joint effects of genetic and environmental factors, which could influence viral-triggered asthma exacerbation severity. We agree with the authors that their results do open interesting questions about therapeutics and timing of therapeutics for asthma—specifically those targeting IgE signaling events. Could anti-IgE then be given acutely during an exacerbation to help reduce the severity of the exacerbation? Certainly, anti-IgE therapy has been shown to prevent viral exacerbations of asthma in the Inner-City Anti-IgE Therapy for Asthma6 study, and shown

to reduce exacerbation numbers even when given 4 to 6 weeks before return to school in the follow-up Preventative Omalizumab or Step-up Therapy for Fall Exacerbations7 study. Looking at antiviral specific IgE in these patients may help to explain these past finding and whether these new treatment strategies should be investigated. Jonathan S. Tam, MDa Mitchell H. Grayson, MDb From aChildren’s Hospital Los Angeles, Los Angeles, Calif; and bNationwide Children’s Hospital/The Ohio State University, Columbus, Ohio. E-mail: jstam@ chla.usc.edu. M.H.G. has received research funding from the National Institutes of Health (grant nos. HL087778 and AI120655) and Polyphor, Ltd. Disclosure of potential conflict of interest: M. H. Grayson has received grants from the National Institutes of Health (grant nos. HL087778 and AI120655) and Polyphor, Ltd; is Deputy Editor for the Annals of Allergy, Asthma, and Immunology; is Abstract Review Chair for the American College of Allergy, Asthma, and Immunology; is a board member for the American Academy of Allergy, Asthma & Immunology; is a member of the Editorial Board for the Journal of Allergy and Clinical Immunology; and is a board member and Medical Science Council Chair for the Asthma and Allergy Foundation of America. J. S. Tam declares no relevant conflicts of interest.

REFERENCES 1. Kantor DB, Stenquist N, McDonald MC, Schultz BJ, Hauptman M, Smallwood CD, et al. Rhinovirus and serum IgE are associated with acute asthma exacerbation severity in children. J Allergy Clin Immunol 2016;138:1467-71.e9. 2. Smith-Norowitz TA, Mandal M, Joks R, Norowitz LT, Weaver D, Durkin HG, et al. IgE anti-respiratory syncytial virus antibodies detected in serum of pediatric patients with asthma. Hum Immunol 2015;76:519-24. 3. Tam JS, Jackson WT, Hunter D, Proud D, Grayson MH. Rhinovirus specific IgE can be detected in human sera. J Allergy Clin Immunol 2013;132:1241-3. 4. Grayson MH, Cheung D, Rohlfing MM, Kitchens R, Spiegel DE, Tucker J, et al. Induction of high-affinity IgE receptor on lung dendritic cells during viral infection leads to mucous cell metaplasia. J Exp Med 2007;204:2759-69. 5. Cheung DS, Ehlenbach SJ, Kitchens T, Riley DA, Grayson MH. Development of atopy by severe paramyxoviral infection in a mouse model. Ann Allergy Asthma Immunol 2010;105:437-43.e431. 6. Busse WW, Morgan WJ, Gergen PJ, Mitchell HE, Gern JE, Liu AH, et al. Randomized trial of omalizumab (anti-IgE) for asthma in inner-city children. N Engl J Med 2011;364:1005-15. 7. Teach SJ, Gill MA, Togias A, Sorkness CA, Arbes SJ Jr, Calatroni A, et al. Preseasonal treatment with either omalizumab or an inhaled corticosteroid boost to prevent fall asthma exacerbations. J Allergy Clin Immunol 2015;136:1476-85. http://dx.doi.org/10.1016/j.jaci.2016.11.055

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