Reduced quantity and function of pneumococcal antibodies are associated with exacerbations of COPD in SPIROMICS

Abstract

While hypogammaglobulinemia is associated with COPD exacerbations, it is unknown whether frequent exacerbators have specific defects in antibody production/function. We hypothesized that reduced quantity/function of serum pneumococcal antibodies correlate with exacerbation risk in the SPIROMICS cohort. We measured total pneumococcal IgG in n = 764 previously vaccinated participants with COPD. In a propensity-matched subset of n = 200 with vaccination within five years (n = 50 without exacerbations in the previous year; n = 75 with one, n = 75 with ≥2), we measured pneumococcal IgG for 23 individual serotypes, and pneumococcal antibody function for 4 serotypes. Higher total pneumococcal IgG, serotype-specific IgG (17/23 serotypes), and antibody function (3/4 serotypes) were independently associated with fewer prior exacerbations. Higher pneumococcal IgG (5/23 serotypes) predicted lower exacerbation risk in the following year. Pneumococcal antibodies are inversely associated with exacerbations, supporting the presence of immune defects in frequent exacerbators. With further study, pneumococcal antibodies may be useful biomarkers for immune dysfunction in COPD.

Keywords: Antibodies; Immunity; Immunoglobulin G; Opsonization; Streptococcus pneumoniae.

Figure 1.

A. Mean total pneumococcal IgG (PnIgG) levels were higher among SPIROMICS participants with fewer ECOPD in the previous year. P-values are from one-way ANOVA with Bonferroni correction for multiple comparisons. B. Higher total PnIgG was associated with having 0 (vs 2+) ECOPD in the previous year in a multivariable logistic regression model that included adjustment for age, sex, race, FEV₁, maximal educational attainment, current smoking at baseline visit, inhaled corticosteroid use, oral corticosteroid use, and timing of pneumococcal vaccination within past 5 years. C-D. Total PnIgG levels at baseline and risk for total (C.) and severe (D.) ECOPD in the first year of longitudinal follow-up, in multivariable negative binomial models that included adjustment for age, sex, race, FEV₁, maximal educational attainment, current smoking at baseline visit, inhaled corticosteroid use, oral corticosteroid use, and timing of pneumococcal vaccination within past 5 years *Odds ratios (OR)/Incidence rate ratios (IRR) indicate the odds (or risk) of greater number of ECOPD with increasing pneumococcal IgG or OI

Figure 2.

A. Mean serotype-specific pneumococcal IgG (PnIgG) levels were higher among SPIROMICS participants with fewer ECOPD in the previous year across a majority of serotypes tested. P-values are from one-way ANOVA with Bonferroni correction for multiple comparisons. B. Higher serotype-specific PnIgG levels were associated with having 0 (vs 2+) ECOPD in the previous year in multivariable logistic regression models that included adjustment for age, sex, race, FEV₁, maximal educational attainment, current smoking at baseline visit, and inhaled corticosteroid use C-D. Serotype-specific PnIgG levels at baseline and risk for total (C.) and severe (D.) ECOPD in the first year of longitudinal follow-up, in multivariable negative binomial models that included adjustment for age, sex, race, FEV₁, maximal educational attainment, current smoking at baseline visit, and inhaled corticosteroid use *Odds ratios (OR)/Incidence rate ratios (IRR) indicate the odds (or risk) of greater number of ECOPD with increasing pneumococcal IgG or OI

Figure 3.

A. Mean opsonic index (OI, a measure of pneumococcal antibody function) was higher among SPIROMICS participants with fewer ECOPD in the previous year in 3 of 4 serotypes tested. P-values are from one-way ANOVA with Bonferroni correction for multiple comparisons. B. For these 3 serotypes, higher OI was associated with having 0 (vs 2+) ECOPD in the previous year in multivariable logistic regression models that included adjustment for age, sex, race, FEV₁, maximal educational attainment, current smoking at baseline visit, and inhaled corticosteroid use C-D. Baseline OI and risk for total (C.) and severe (D.) ECOPD in the first year of longitudinal follow-up, in multivariable negative binomial models that included adjustment for age, sex, race, FEV₁, maximal educational attainment, current smoking at baseline visit, and inhaled corticosteroid use *Odds ratios (OR)/Incidence rate ratios (IRR) indicate the odds (or risk) of greater number of ECOPD with increasing pneumococcal IgG or OI