Asthma is a common comorbidity in patients with immunoglobulin G subclass deficiency (IGGSCD).1,2 Patients with asthma and IGGSCD often have recurrent respiratory infections, which contribute to asthma exacerbation and severity and lung function decline.3,4 In this study, we investigated functional defects in B lymphocytes in adult asthmatic patients with IGGSCD and analyzed them in relation to clinical parameters.
A total of 44 patients were enrolled in this study; 17 were asthmatic patients with IGGSCD, and the remainder were those without IGGSCD. Among the patients with IGGSCD, immunoglobulin (Ig) G3 subclass deficiency was the most common type (15/17, 88.2%). The male to female ratio was 16:28, and the median age was 52.5 years (interquartile range [IQR], 44.0–60.8 years). The median percentage of the forced expiratory volume in one second (FEV1) of the asthmatic patients with IGGSCD and those without IGGSCD was 80.8% (65.3–98.7) and 87.3% (72.9–100.0), respectively (Supplementary Table S1). To assess B lymphocyte function, a [3H]-thymidine incorporation assay and flow cytometry to measure CD23 expression on peripheral blood mononuclear cells were performed after the stimulation with anti-CD40/interleukin (IL)-4 according to the protocols of a previous study.5,6 This study was approved by Institutional Review Board of Ajou University Medical Center (AJOUIRB-KSP-2020-158), and all study patients provided informed consent.
When cell proliferation was compared according to the presence or absence of IGGSCD, the fold change in [3H] thymidine-incorporated cells was significantly lower in asthmatic patients with IGGSCD than in those without (median, 2.45 [IQR, 1.30–3.78] vs. 3.69 [1.97–7.52], P = 0.054; Figure A). CD23+CD3−CD19+ cells (%) were significantly lower in asthmatic patients with IGGSCD than in those without (median, 41.10 [IQR, 8.16–69.20] vs. 65.20 [56.20–72.00], P = 0.026; Figure B). We further analyzed them according to the severity of asthma (severe asthma vs. non-severe asthma), which was defined according to the American Thoracic Society/European Respiratory Society guidelines.7 The patients with severe asthma (SA) (22/44, 50%) showed a significantly decreased fold change in [3H] thymidine-incorporated cells and the percentage of CD23+CD3−CD19+ cells compared to those with non-severe asthma (NSA) (median, 2.32 [IQR, 1.28–4.21] vs. 3.81 [2.62–8.42] for proliferation assay and 53.9% [23.04–65.75] vs. 68.80 [56.70–73.65] for CD23+CD3−CD19+ cells, P = 0.008, and P = 0.011, respectively; Figure C and D). Among the patients with IGGSCD, B lymphocytes from the patients with SA were less proliferated and less expressed CD23 antigen than those with NSA (P = 0.364 and P = 0.050, respectively; Figure E and F). In all asthmatic patients, CD23+CD3−CD19+ cells (%) correlated with lung function parameters such as FEV1% and FEV1/forced vital capacity (FVC) (r = 0.387, P = 0.011 for FEV1%, and r = 0.392, P = 0.010 for FEV1/FVC, respectively; Figure G and H). The patients with SA showed a strong positive correlation between CD23+CD3−CD19+ cells (%) and FEV1% (r = 0.521, P = 0.015, data was not shown). However, no correlation was noted in the subgroup of patients with/without IGGSCD.
Figure. Comparisons of cell proliferation (A, C, E) and the percentage of CD23 expression (B, D, F) of B lymphocytes under anti-CD40/IL-4 stimulation according to the presence of IGGSCD and asthma severity. Correlation of CD23 expression in B lymphocytes with FEV1 (%) or FEV1/FVC (G, H) in all subjects. Cell proliferation data (A, C, E) are presented as a fold increase in [3H]-thymidine incorporation, and the percentages of CD23 expression (B, D, F) are presented as median and interquartile ranges.
IL, interleukin; IGGSCD, immunoglobulin G subclass deficiency; FEV1, forced expiratory volume in one second; FVC, forced vital capacity.
This study demonstrated that B lymphocyte proliferation and activation were significantly decreased in asthmatic patients with IGGSCD compared to those without. Furthermore, B-cell proliferation and activation were lower in patients with SA than in those with NSA. In addition, there was a significant association between the percentage of CD23 expression in response to anti-CD40/IL-4 stimulation and lung function parameters, suggesting that functional defects in B lymphocytes were involved in the pathogenesis of IGGSCD and related to the severity of asthma. However, these require further validation in a larger cohort. In conclusion, functional defects in B lymphocytes exist in asthmatic patients with IGGSCD in which CD23 expression is associated with clinical outcomes.
ACKNOWLEDGMENTS
This research was supported by the Basic Science Research Program of the National Research Foundation (NRF) grant funded by the Korea government (NRF-2021R1A2B5B01001767) and the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) grant funded by the Ministry of Health and Welfare, Republic of Korea (Grant No. HR16C0001) and partly supported by Green Cross, Korea.
Footnotes
Disclosure: There are no financial or other issues that might lead to conflict of interest.
SUPPLEMENTARY MATERIAL
Baseline characteristics of the study subjects
References
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Supplementary Materials
Baseline characteristics of the study subjects