Airway and Systemic Immunoglobulin Profiling and Immune Response in Adult Asthma

Author:

Walsh Laura J.ORCID,Sullivan Ashley,Ward ChrisORCID,Hunt Eoin B.,Lapthorne Susan,Eustace Joseph A.,Fanning Liam J.ORCID,Plant Barry J.ORCID,O’Byrne Paul M.ORCID,MacSharry John A.ORCID,Murphy Desmond M.ORCID

Abstract

Abstract Introduction Immunoglobulins play a vital role in host immune response and in the pathogenesis of conditions like asthma. Therapeutic agents such as monoclonal antibodies target specific elements of the asthmatic inflammatory cascade. Decisions to utilize these medications are often based on systemic inflammatory profiling without direct insight into the airway inflammatory profile. We sought to investigate the relationship between immunoglobulin and cytokine profiles in the airway and systemic immune compartments of adult asthmatics. Methods Blood sampling and bronchoscopy with bronchoalveolar lavage (BAL) were performed in 76 well-defined adult asthmatics. Antibody and cytokine profiles were measured in both BAL and serum using ELISA and quantibody arrays. Results There was no relationship between BAL and serum levels of IgE. This is of significance in an asthma population. For some analytes, correlation analysis was significant (P < 0.05) indicating representativeness of our cohort and experimental setup in those cases. Nevertheless, the predictive power (r2) of the BAL-to-serum comparisons was mostly low except for TNF-α (r2 = 0.73) when assuming a simple (linear) relationship. Conclusion This study highlights the importance of sample site when investigating the roles of immunoglobulins and cytokines in disease pathogenesis and suggests that both localized and systemic immune responses are at play. The prescription of asthma monoclonal therapy is generally based on systemic evaluation of cytokine and immunoglobulin levels. Our research suggests that this approach may not fully reflect the pathophysiology of the disease and may provide insight into why some patients respond to these targeted therapies while others do not.

Funder

Wilton Respiratory Research Fund

European Respiratory Society short-term research fellowship STRF 2018

Denis O’ Sullivan Fellowship

University College Cork School of Medicine TRAP award

The Irish Lung Foundation

The APC Microbiome Ireland Innovation Fund with the financial support of Science Foundation Ireland

University College Cork

Publisher

Springer Science and Business Media LLC

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