Lower serum IgA is associated with COPD exacerbation risk in SPIROMICS

Abstract

Background: Decreased but measurable serum IgA levels (≤70 mg/dL) have been associated with risk for infections in some populations, but are unstudied in COPD. This study tested the hypothesis that subnormal serum IgA levels would be associated with exacerbation risk in COPD.

Methods: Data were analyzed from 1,049 COPD participants from the observational cohort study SPIROMICS (535 (51%) women; mean age 66.1 (SD 7.8), 338 (32%) current smokers) who had baseline serum IgA measured using the Myriad RBM biomarker discovery platform. Exacerbation data was collected prospectively (mean 944.3 (SD 281.3) days), and adjusted linear, logistic and zero-inflated negative binomial regressions were performed.

Results: Mean IgA was 269.1 mg/dL (SD 150.9). One individual had deficient levels of serum IgA (<7 mg/dL) and 25 (2.4%) had IgA level ≤70 mg/dL. Participants with IgA ≤70 mg/dL were younger (62 vs. 66 years, p = 0.01) but otherwise similar to those with higher IgA. In adjusted models, IgA ≤70 mg/dL was associated with higher exacerbation incidence rates (IRR 1.71, 95% CI 1.01-2.87, p = 0.044) and greater risk for any severe exacerbation (OR 2.99, 95% CI 1.30-6.94, p = 0.010). In adjusted models among those in the lowest decile (<120 mg/dL), each 10 mg/dL decrement in IgA (analyzed continuously) was associated with more exacerbations during follow-up (β 0.24, 95% CI 0.017-0.46, p = 0.035).

Conclusions: Subnormal serum IgA levels were associated with increased risk for acute exacerbations, supporting mildly impaired IgA levels as a contributing factor in COPD morbidity. Additionally, a dose-response relationship between lower serum IgA and number of exacerbations was found among individuals with serum IgA in the lowest decile, further supporting the link between serum IgA and exacerbation risk. Future COPD studies should more comprehensively characterize immune status to define the clinical relevance of these findings and their potential for therapeutic correction.

Conflict of interest statement

Competing Interests: NP has received a grant from the National Institutes of Health unrelated to this work but has no relevant conflicts of interest. MBD has no relevant conflicts of interest related to this work. He has received grants from the National Institutes of Health unrelated to this work. GGP reports no relevant conflicts of interest. JLC reports grants from NIH/NHLBI during the conduct of the study; and grants from MedImmune Corp. Ltd., Department of Veterans Affairs, NIH/NIAID, and Department of Defense outside the scope of the submitted work. RPB reports no relevant conflicts of interest. AF reports no relevant conflicts of interest. MKH reports consulting for GSK, BI, and AstraZeneca as well as in kind research support from Novartis and Sunovion. REK reports no relevant conflicts of interest. MTD has received grants from NIH and the Department of Defense, consulting fees from AstraZeneca, Boerhinger Ingelheim, Genentech, GlaxoSmithKline, and PneumRx/BTG and contracted clinical trial funding from AstraZeneca, Boerhinger Ingelheim, GlaxoSmithKline, Yungjin, PneumRx/BTG, Pulmonx, Novartis, and Boston Scientific. APC reports consulting for VIDA Diagnostics. AAL reports no conflicts of interest. NNH reports grants and personal fees from AstraZeneca, grants and personal fees from GSK, grants from Boehringer Ingelheim, grants from NIH, grants from COPD Foundation, outside the submitted work. PGW reports personal fees from Astra Zeneca, personal fees from Regeneron, personal fees from Sanofi, personal fees from Genentech, personal fees from Janssen, outside the submitted work. RP reports grants from NHLBI, grants from COPD Foundation, during the conduct of the study; grants from Department of Veterans Affairs, grants from NHLBI, outside the submitted work. LMP reports no relevant conflicts of interest. WKO reports no relevant conflicts of interest. RAW reports no conflicts relevant to the current work. outside the scope of the submitted work, he reports grants and personal fees from AstraZeneca, GlaxoSmithKline, and Boehringer Ingelheim, and personal fees from Contrafect, Pfizer, Pulmonx, Spiration, Sunovion, Teva, Merck, and Bonti. AA reports no relevant conflicts of interest. The above listed conflicts of interest do not alter the authors’ adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1. Distribution of serum IgA by gender.

Fig 2. Unadjusted association of IgA with follow-up exacerbations among lowest decile IgA(0–120 mg/dL).