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Serum sCD163 as a biomarker of adipose tissue inflammation in obstructive sleep apnoea patients: limits and perspectives

Silke Ryan
European Respiratory Journal 2017 50: 1701182; DOI: 10.1183/13993003.01182-2017
Silke Ryan
1Pulmonary and Sleep Disorders Unit, St. Vincent's University Hospital, Dublin, Ireland
2School of Medicine, The Conway Institute, University College Dublin, Dublin, Ireland
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Abstract

sCD163 in sleep apnoea requires further evaluation http://ow.ly/o3R130d82YZ

From the author:

I thank D. Monneret and J-P. Bastard for their interest in our manuscript [1] and I could not agree more with their comment that the role of soluble CD163 (sCD163) in obstructive sleep apnoea (OSA) requires further detailed evaluation. As outlined in our article, the measurement of sCD163 in our patient cohort followed our results from the in vitro and in vivo studies demonstrating M1 polarisation of adipose tissue macrophages in response to intermittent hypoxia and thus, was not an a priori hypothesis of our study. Nonetheless, the detected independent association of sCD163 with OSA severity is intriguing.

CD163 is a haemoglobin scavenger receptor that is expressed by cells of the monocyte-M2-macrophage lineage [2]. The soluble form of CD163 is present in plasma of healthy individuals [3] but in response to several inflammatory mediators, levels rise acutely due to metalloproteinase-17/tumour necrosis factor-α-converting enzyme (ADAM17/TACE)-mediated cleavage [4–6]. sCD163 has emerged as a sensitive biomarker of inflammation and increased levels have been found in numerous pro-inflammatory conditions, i.e. sepsis, hepatitis, rheumatoid arthritis, scleroderma or atherosclerosis [7, 8]. Moreover, sCD163 is increasingly linked with adipose tissue inflammation and is considered a prognostic predictor for the development of type 2 diabetes [9–11]. Taken all this information together, sCD163 is a very attractive target in OSA.

In our cross-sectional study, univariate analysis revealed a significant correlation of sCD163 with all OSA severity parameters but also with body mass index and waist/hip ratio. However, in linear regression, adjusted for anthropometric and demographic parameters, the apnoea/hypopnoea index (AHI) (or oxygen desaturation index, when substituted for AHI) remained the only significant predictor of this response. Hence, these results along with the pre-clinical data generate the hypothesis that sCD163 may serve as a potential pro-inflammatory marker and predictor of metabolic consequences in OSA. However, testing this hypothesis, as acknowledged in our manuscript, warrants further targeted evaluation including large prospective studies.

Footnotes

  • Conflict of interest: None declared.

  • Received June 14, 2017.
  • Accepted June 16, 2017.
  • Copyright ©ERS 2017

References

  1. ↵
    1. Murphy AM,
    2. Thomas A,
    3. Crinion SJ
    , et al. Intermittent hypoxia in obstructive sleep apnoea mediates insulin resistance through adipose tissue inflammation. Eur Respir J 2017; 49: 1601731.
    OpenUrlAbstract/FREE Full Text
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    1. Kristiansen M,
    2. Graversen JH,
    3. Jacobsen C
    , et al. Identification of the haemoglobin scavenger receptor. Nature 2001; 409: 198–201.
    OpenUrlCrossRefPubMedWeb of Science
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    1. Møller HJ,
    2. Peterslund NA,
    3. Graversen JH
    , et al. Identification of the hemoglobin scavenger receptor/CD163 as a natural soluble protein in plasma. Blood 2002; 99: 378–380.
    OpenUrlAbstract/FREE Full Text
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    1. Etzerodt A,
    2. Maniecki MB,
    3. Møller K
    , et al. Tumor necrosis factor alpha-converting enzyme (TACE/ADAM17) mediates ectodomain shedding of the scavenger receptor CD163. J Leukoc Biol 2010; 88: 1201–1205.
    OpenUrlAbstract/FREE Full Text
    1. Hintz KA,
    2. Rassias AJ,
    3. Wardwell K
    , et al. Endotoxin induces rapid metalloproteinase-mediated shedding followed by up-regulation of the monocyte hemoglobin scavenger receptor CD163. J Leukoc Biol 2002; 72: 711–717.
    OpenUrlAbstract/FREE Full Text
  5. ↵
    1. Matsushita N,
    2. Kashiwagi M,
    3. Wait R
    , et al. Elevated levels of soluble CD163 in sera and fluids from rheumatoid arthritis patients and inhibition of the shedding of CD163 by TIMP-3. Clin Exp Immunol 2002; 130: 156–161.
    OpenUrlCrossRefPubMedWeb of Science
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    1. Buechler C,
    2. Eisinger K,
    3. Krautbauer S
    . Diagnostic and prognostic potential of the macrophage specific receptor CD163 in inflammatory diseases. Inflamm Allergy Drug Targets 2013; 12: 391–402.
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    1. Etzerodt A,
    2. Moestrup SK
    . CD163 and inflammation: biological, diagnostic, and therapeutic aspects. Antioxid Redox Signal 2013; 18: 2352–2363.
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  8. ↵
    1. Kračmerová J,
    2. Rossmeislová L,
    3. Kováčová Z
    , et al. Soluble CD163 is associated with CD163 mRNA expression in adipose tissue and with insulin sensitivity in steady-state condition but not in response to calorie restriction. J Clin Endocrinol Metab 2014; 99: E528–E535.
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    1. Møller HJ,
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    3. Moestrup SK
    , et al. Serum soluble CD163 predicts risk of type 2 diabetes in the general population. Clin Chem 2011; 57: 291–297.
    OpenUrlAbstract/FREE Full Text
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    1. Parkner T,
    2. Sorensen LP,
    3. Nielsen AR
    , et al. Soluble CD163: a biomarker linking macrophages and insulin resistance. Diabetologia 2012; 55: 1856–1862.
    OpenUrlCrossRefPubMedWeb of Science
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Serum sCD163 as a biomarker of adipose tissue inflammation in obstructive sleep apnoea patients: limits and perspectives
Silke Ryan
European Respiratory Journal Aug 2017, 50 (2) 1701182; DOI: 10.1183/13993003.01182-2017

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Serum sCD163 as a biomarker of adipose tissue inflammation in obstructive sleep apnoea patients: limits and perspectives
Silke Ryan
European Respiratory Journal Aug 2017, 50 (2) 1701182; DOI: 10.1183/13993003.01182-2017
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