Analysis of Immunoglobulin A and M gene expression and plasma cells in bronchial tissue from COPD patients with high blood eosinophil counts
T. Southworth (Manchester, United Kingdom), U. Kolsum (Manchester, United Kingdom), A. Higham (Manchester, United Kingdom), S. Sridhar (Gaithersburg, United States of America), T. Pham (Gaithersburg, United States of America), P. Newbold (Gaithersburg, United States of America), D. Singh (Manchester, United Kingdom)
Source: International Congress 2018 – Advanced profiling of immune cells in chronic lung diseases
Disease area: Airway diseases
Abstract Background : COPD patients with higher sputum or blood eosinophil counts have greater clinical response to corticosteroids and suffer lower bacterial colonisation (Kolsum et al, Respir Res 2017). Recently we have shown that these patients have higher levels of immunoglobulin (Ig) A and M proteins in their bronchoalveolar lavage (Kolsum et al, JACI 2017).
Aims : To compare immunoglobulin and plasma cell gene expression in bronchial brushings from eosinophil high and low COPD patients.
Methods : 21 eosinophil low (blood count <150/µl) and 20 eosinophil high (>250/µl) COPD patients were recruited for bronchoscopy. Following RNA sequencing, the STAR pipeline was used to quantify bronchial brush gene expression. Differentially expressed genes and immune-related signatures were compared in eosinophil high vs low groups by ANOVA.
Results : Genes relating to IgA and IgM had greater expression in eosinophil high patients (Table 1). A plasma cell gene signature (TNFRSF17, IGKC, IGKV4-1, IGHA1) was on average expressed higher in eosinophil high patients (p=0.03)
Table 1: Comparison of IgA and IgM gene expression in eosinophil high and low patients.
gene
Fold change (high/low)
p-value (high v low)
IGHA2
7.9
0.001
JCHAIN
5.3
0.005
IGHA1
5.0
0.006
IGHM
4.1
0.01
Conclusions : COPD patients with higher blood eosinophils, have more IgA, IgM and increased plasma cell gene signature in the bronchial airway. While this may play a role in reducing bacterial colonisation in these patients, further work is required to determine if this is a direct role of eosinophils or whether this is secondary to the higher, local inflammation observed in eosinophilic COPD patients.
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T. Southworth (Manchester, United Kingdom), U. Kolsum (Manchester, United Kingdom), A. Higham (Manchester, United Kingdom), S. Sridhar (Gaithersburg, United States of America), T. Pham (Gaithersburg, United States of America), P. Newbold (Gaithersburg, United States of America), D. Singh (Manchester, United Kingdom). Analysis of Immunoglobulin A and M gene expression and plasma cells in bronchial tissue from COPD patients with high blood eosinophil counts. 4924
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