The impact of IgG subclass deficiency on the risk of mortality in hospitalized patients with COPD

Hyun Lee, Cara Kovacs, Andre Mattman, Zsuzsanna Hollander, Virginia Chen, Raymond Ng, Janice M Leung, Don D Sin, Hyun Lee, Cara Kovacs, Andre Mattman, Zsuzsanna Hollander, Virginia Chen, Raymond Ng, Janice M Leung, Don D Sin

Abstract

Background: Immunoglobulin G (IgG) deficiency increases the risk of acute exacerbations and mortality in chronic obstructive pulmonary disease (COPD). However, the impact of IgG subclass deficiency on mortality in COPD is unknown. Here, we determined which IgG subclass, if any, is associated with increased risk of mortality in COPD.

Methods: We measured serum IgG subclass concentrations of 489 hospitalized patients with COPD who were enrolled in the Rapid Transition Program (clinicaltrials.gov identifier NCT02050022). To evaluate the impact of IgG subclass deficiency on 1-year mortality, Cox proportional hazards regression analyses were performed with adjustments for potential confounders.

Results: Deficiencies in IgG1, IgG2, IgG3, and IgG4 were present in 1.8%, 12.1%, 4.3%, and 11.2% of patients, respectively. One-year mortality was 56% in patients with IgG1 deficiency, 27% in IgG2 deficiency, 24% in IgG3 deficiency, and 31% in IgG4 deficiency. Cox proportional modeling showed that IgG1 and IgG4 deficiencies increased the 1-year mortality risk with an adjusted hazard ratio of 3.92 (95% confidence interval [CI] = 1.55-9.87) and 1.74 (95% CI = 1.02-2.98), respectively. Neither IgG2 nor IgG3 deficiency significantly increased 1-year mortality. Two or more IgG subclass deficiencies were observed in 5.3%. Patients with 2 or more IgG subclass deficiencies had a higher 1-year mortality than those without any deficiencies (46.2% vs. 19.7%, p < 0.001), with an adjusted hazard ratio of 2.22 (95% CI = 1.18-4.17).

Conclusions: IgG1 and IgG4 deficiency was observed in 1.8% and 11.2% of hospitalized patients with COPD, respectively, and these deficiencies were associated with a significantly increased risk of 1-year mortality.

Keywords: COPD; IgG; IgG subclass deficiency; Mortality.

Conflict of interest statement

The authors declare that they have no competing interests.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Study flow chart. *Some patients had two or more IgG subclass deficiencies. IgG immunoglobulin G
Fig. 2
Fig. 2
Kaplan–Meier survival curves for mortality according to IgG subclass deficiency (a) IgG1 deficiency; (b) IgG2 deficiency; (c) IgG3 deficiency; (d) IgG4 deficiency. IgG immunoglobulin G
Fig. 3
Fig. 3
Kaplan–Meier survival curves for mortality according to the number of IgG subclass deficiencies. Bonferroni adjustment was performed for multiple comparisons. IgG immunoglobulin G

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