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Complement C3 and allergic asthma: a cohort study of the general population

Signe Vedel-Krogh, Katrine L. Rasmussen, Børge G. Nordestgaard, Sune F. Nielsen
European Respiratory Journal 2021 57: 2000645; DOI: 10.1183/13993003.00645-2020
Signe Vedel-Krogh
1Dept of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark
2Dept of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
3Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark
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Katrine L. Rasmussen
1Dept of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark
2Dept of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
3Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark
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Børge G. Nordestgaard
1Dept of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark
3Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark
4Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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Sune F. Nielsen
1Dept of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark
3Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark
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Abstract

Complement C3 plays a role in asthma development and severity. We tested the hypothesis that high plasma complement C3 concentration is associated with high risks of asthma hospitalisation and exacerbation.

We prospectively assessed the risk of asthma hospitalisation in 101 029 individuals from the Copenhagen General Population Study with baseline measurements of plasma complement C3, and genotyped for rs1065489, rs429608 and rs448260 determining levels of complement C3. Risk of asthma exacerbation was further assessed in 2248 individuals with allergic asthma.

The multivariable adjusted hazard ratio of asthma hospitalisation was 1.23 (95% CI 1.04–1.45) for individuals in the highest tertile (>1.19 g·L−1) of plasma complement C3 compared with those in the lowest tertile (<1.03 g·L−1). The C3 rs448260 genotype was associated with risk of asthma hospitalisation with an observed hazard ratio of 1.17 (95% CI 1.06–1.28) for the CC genotype compared with the AA genotype. High plasma complement C3 was associated with high levels of blood eosinophils and IgE (p for trends ≤6×10−9), but only the SKIV2L rs429608 genotype was positively associated with blood eosinophil count (p=3×10−4) and IgE level (p=3×10−4). In allergic asthma, the multivariable adjusted incidence rate ratio for risk of exacerbation was 1.69 (95% CI 1.06–2.72) for individuals in the highest plasma complement C3 tertile (>1.24 g·L−1) versus the lowest (<1.06 g·L−1).

In conclusion, a high concentration of plasma complement C3 was associated with a high risk of asthma hospitalisation in the general population and with a high risk of asthma exacerbation in individuals with allergic asthma. Our findings support a causal role of the complement system in asthma severity.

Abstract

High concentrations of plasma complement C3 are associated with asthma hospitalisation and exacerbation risk among individuals from the general population; genetic analyses indicate a causal role for complement C3 in asthma pathogenesis and severity https://bit.ly/30PIIwg

Footnotes

  • This article has supplementary material available from erj.ersjournals.com

  • Author contributions: S. Vedel-Krogh, K.L. Rasmussen, B.G. Nordestgaard and S.F. Nielsen designed the study together. S. Vedel-Krogh analysed the data. S.F. Nielsen oversaw all analyses and contributed to the interpretation of data. S. Vedel-Krogh wrote the first draft of the paper and K.L. Rasmussen, B.G. Nordestgaard and S.F. Nielsen edited the paper. All authors approved this paper in its final form.

  • Conflict of interest: S. Vedel-Krogh has nothing to disclose.

  • Conflict of interest: K.L. Rasmussen has nothing to disclose.

  • Conflict of interest: B.G. Nordestgaard has nothing to disclose.

  • Conflict of interest: S.F. Nielsen has nothing to disclose.

  • Support statement: The study was funded by the Dept of Clinical Biochemistry, Herlev and Gentofte Hospital. The sponsor of the study had no role in study design, data collection, data analysis, data interpretation or writing of the paper. Funding information for this article has been deposited with the Crossref Funder Registry.

  • Received March 11, 2020.
  • Accepted August 10, 2020.
  • Copyright ©ERS 2021
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Vol 57 Issue 2 Table of Contents
European Respiratory Journal: 57 (2)
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Complement C3 and allergic asthma: a cohort study of the general population
Signe Vedel-Krogh, Katrine L. Rasmussen, Børge G. Nordestgaard, Sune F. Nielsen
European Respiratory Journal Feb 2021, 57 (2) 2000645; DOI: 10.1183/13993003.00645-2020

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Complement C3 and allergic asthma: a cohort study of the general population
Signe Vedel-Krogh, Katrine L. Rasmussen, Børge G. Nordestgaard, Sune F. Nielsen
European Respiratory Journal Feb 2021, 57 (2) 2000645; DOI: 10.1183/13993003.00645-2020
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