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

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.

Changes in Serum Immunoglobulin G Subclasses during the Treatment of Patients with Chronic Obstructive Pulmonary Disease with Infectious Exacerbations

“…A study on 59 adult patients with asthma and stable COPD in Korea found that IgG subclass deficiency was the most common phenotype (67%), followed by total IgG deficiency (20%), in which IgG3 and IgG4 were the most affected subclasses [ 15 ]. Low serum IgG levels were associated with an increased risk for recurrent acute exacerbations, lower respiratory infections, a decline in lung function, and hospitalization [ 25 , 32 ]. However, the IgG3 levels at time T1 were significantly higher than those at time T2.…”

Innate and Adaptive Immunity during SARS-CoV-2 Infection: Biomolecular Cellular Markers and Mechanisms

“…IgG1 and IgG3 were initially associated with severe disease in older adults with COVID-19 (n = 123) disease and accompanying irregularities in neutralizing antibodies (nAbs), chemokines, and T cell responses, which is an anomaly as IgG3 was previously thought to provide enhanced pathogen response [ 91 , 119 , 120 ]. However, IgG deficiency has been observed to be associated with increased mortality risk in Chronic Obstructive Pulmonary Disease (COPD) patients (n = 489) in these ratios: 56% IgG1: 27%: IgG2: 24% IgG3: 31% IgG4 [ 120 ].…”

“…IgG1 and IgG3 were initially associated with severe disease in older adults with COVID-19 (n = 123) disease and accompanying irregularities in neutralizing antibodies (nAbs), chemokines, and T cell responses, which is an anomaly as IgG3 was previously thought to provide enhanced pathogen response [ 91 , 119 , 120 ]. However, IgG deficiency has been observed to be associated with increased mortality risk in Chronic Obstructive Pulmonary Disease (COPD) patients (n = 489) in these ratios: 56% IgG1: 27%: IgG2: 24% IgG3: 31% IgG4 [ 120 ]. A previous study (n = 105) comparing serology of hCoV-229E, hCoV-OC43, hCoV-NL63, and hCoV-HKU1 elucidated that participants show in other hCoV antibody responses with regard to IgG that were 99%:100%:98%:91%, with IgA in nasal wash samples, detected in between 8% and 31% of participants [ 121 ].…”

Cellular and Humoral Immunity and Infection Responses to SARS-CoV-2:Immune Biomolecular Mechanisms by Case Study within SARS-CoV-2 Pathogenesis and Other Infections

“…Responses in SARS-CoV2 Infection IgG1 and IgG3 were initially associated with severe disease (n=123) in COVID-19 disease in older age groups with accompanying irregularities in neutralizing antibodies, chemokines and T cell responses which is an anomaly, as IgG3 was previously thought to provide enhanced pathogen responses [122,123]. However, IgG deficiency has been observed to be associated with increased mortality risk in Chronic Obstructive Pulmonary Disease (COPD) patients (n=489) in these ratios 56% IgG1: 27%: IgG2: 24% IgG3: 31% IgG4 [124]. A previous study (n=105) comparing serology of hCoV-229E, hCoV-OC43, hCoV-NL63 and hCoV-HKU1 elucidated that participants show an antibody response with respective IgG responses as 99%:100%:98%: 91% with IgA in nasal wash samples detected between 8% to 31% of participants [125].…”