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Alterations of HDL particle phospholipid composition and role of inflammation in rheumatoid arthritis

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Abstract

The increased cardiovascular risk in RA (rheumatoid arthritis) cannot be explained by common quantitative circulating lipid parameters. The objective of the study was to characterize the modifications in HDL phosphosphingolipidome in patients with RA to identify qualitative modifications which could better predict the risk for CVD. Nineteen patients with RA were compared to control subjects paired for age, sex, BMI, and criteria of metabolic syndrome. The characterization of total HDL phosphosphingolipidome was performed by LC-MS/MS. RA was associated with an increased HDL content of lysophosphatidylcholine and a decreased content of PC (phosphatidylcholine), respectively, positively and negatively associated with cardiovascular risk. A discriminant molecular signature composed of 18 lipids was obtained in the HDL from RA patients. The detailed analysis of phospholipid species showed that molecules carrying omega-3 FA (fatty acids), notably docosahexaenoic acid (C22:6 n-3), were depleted in HDL isolated from RA patients. By contrast, two PE (phosphatidylethanolamine) species carrying arachidonic acid (C20:4 n-6) were increased in HDL from RA patients. Furthermore, disease activity and severity indexes were associated with altered HDL content of 4 PE and 2 PC species. In conclusion, the composition of HDL phosphosphingolipidome is altered during RA. Identification of a lipidomic signature could therefore represent a promising biomarker for CVD risk. Although a causal link remains to be demonstrated, pharmacological and nutritional interventions targeting the normalization of the FA composition of altered phospholipids could help to fight against RA-related inflammation and CVD risk.

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Abbreviations

apoA1:

apolipoprotein A1

apoB:

apolipoprotein B

Cer:

ceramides

CRP:

c-reactive protein

HOMA-IR:

Homeostatic Model Assessment of Insulin Resistance

LPC:

lysophosphatidylcholine

NSAIDs:

nonsteroidal anti-inflammatory drugs

PA:

phosphatidic acid

PC:

phosphatidylcholine

PE:

phosphatidylethanolamine

PG:

phosphatidylglycerol

PI:

phosphatidylinositol

PL:

phospholipids

PS:

phosphatidylserine

RA:

rheumatoid arthritis

SCORE:

Systematic COronary Risk Evaluation

SL:

sphingolipids

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Acknowledgments

We are grateful to Jean Paul Rigaudière, Chrystèle Jouve and Sarah de Saint Vincent for their technical assistance.

Availability of data and material

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Funding

This work was supported by a grant from the French Minister of health (PHRC RCVRIC AOI 2014) and from UCB (“Bourse Sirius”).

Author information

Authors and Affiliations

  1. Service de rhumatologie, CHU de Clermont-Ferrand, Université Clermont-Auvergne INRA, 63003, Clermont-Ferrand, France

    Charlotte Giraud, Anne Tournadre & Martin Soubrier

  2. DRCI, CHU de Clermont-Ferrand, 63003, Clermont-Ferrand, France

    Bruno Pereira

  3. CNRS, LaPSCo, Physiological and Psychosocial Stress, CHU Clermont-Ferrand, University Hospital of Clermont-Ferrand, Occupational and Preventive Medicine, WittyFit, Université Clermont Auvergne, Clermont-Ferrand, France

    Frédéric Dutheil

  4. ICANalytics, Institute of Cardiometabolism and Nutrition (IHU-ICAN, ANR-10-IAHU-05), 75013, Paris, France

    Marie Lhomme

  5. INSERM, UMR_S 1166, Integrative Biology of Atherosclerosis Team, Sorbonne Université, 75013, Paris, France

    Anatol Kontush

  6. Unité de Nutrition Humaine (UNH), INRA/Université Clermont Auvergne, 63009, Clermont-Ferrand, France

    Jean-Louis Sébédio & Frédéric Capel

  7. UFR Medecine, UMR1019, Equipe ASMS, 28 place Henri Dunant-BP-38, 63001, Clermont-Ferrand Cedex 1, France

    Frédéric Capel

Authors
  1. Charlotte Giraud
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  2. Anne Tournadre
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  3. Bruno Pereira
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  4. Frédéric Dutheil
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  5. Martin Soubrier
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  6. Marie Lhomme
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  7. Anatol Kontush
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  8. Jean-Louis Sébédio
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  9. Frédéric Capel
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Corresponding author

Correspondence to Frédéric Capel.

Ethics declarations

Competing interests

The authors declare that they have no competing interests.

Ethics approval and consent to participate

The study was approved by the local ethics committee (Institutional Review Boards: 2014-A01847-40). All patients received verbal and written information and signed a consent form prior to inclusion. Control subjects were recruited via advertisements. They provided written informed consent. The RESOLVE study was reviewed and approved by the human ethics committees from St Etienne, France.

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Key points

• RA induced alterations in phospholipid and sphingolipid composition of HDL

• Phospholipids carrying omega-3 fatty acids were depleted during RA

• HDL lipidome was associated with disease activity and severity

• A signature composed of 18 lipids allowed to discriminate patients and controls

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Giraud, C., Tournadre, A., Pereira, B. et al. Alterations of HDL particle phospholipid composition and role of inflammation in rheumatoid arthritis. J Physiol Biochem 75, 453–462 (2019). https://doi.org/10.1007/s13105-019-00694-4

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  • DOI: https://doi.org/10.1007/s13105-019-00694-4

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