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Lipidomic differentiation of Graves’ ophthalmopathy in plasma and urine from Graves’ disease patients

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Abstract

Approximately 50% of patients with Graves’ disease (GD) develop retracted eyelids with bulging eyes, known as Graves’ ophthalmopathy (GO). However, no simple diagnostic blood marker for distinguishing GO from GD has been developed yet. The objective of this study was to conduct comprehensive profiling of lipids using plasma and urine samples from patients with GD and GO undergoing antithyroid therapy using nanoflow ultrahigh performance liquid chromatography electrospray ionization tandem mass spectrometry. Plasma (n = 86) and urine (n = 75) samples were collected from 23 patients with GD without GO, 31 patients with GO, and 32 healthy controls. Among 389 plasma and 273 urinary lipids that were structurally identified, 281 plasma and 191 urinary lipids were quantified in selected reaction monitoring mode. High-abundance lipids were significantly altered, indicating that the development of GD is evidently related to altered lipid metabolism in both plasma and urine. Several urinary lysophosphatidylcholine species were found to be increased (3- to 10-fold) in both GD and GO. While the overall lipid profiles between GD and GO were similar, significant changes (area under receiver operating curve > 0.8) in GO vs. GD were observed in a few lipid profiles: 58:7-TG and (16:1,18:0)-DG from plasma, 16:1-PC and 50:1-TG from urine, and d18:1-S1P from both plasma and urine samples. An altered metabolism of lipids associated with the additional development of ophthalmopathy was confirmed with the discovery of several candidate markers. These can be suggested as candidate markers for differentiating the state of GO and GD patients based on plasma or urinary lipidomic analysis.

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Abbreviations

ApoAV:

Apolipoprotein AV

Cer:

Ceramides

CID:

Collision-induced dissociation

DG:

Diacylglycerol

GD:

Graves’ disease

GO:

Graves’ ophthalmopathy

IS:

Internal standard

LPC:

Lysophosphatidylcholine

LPE:

Lysophosphatidylethanolamine

MS:

Mass spectrometry

nUPLC-ESI-MS/MS:

Nanoflow ultrahigh performance liquid chromatography-electrospray ionization tandem mass spectrometry

PC:

Phosphatidylcholine

PG:

Phosphatidylglycerol

PL:

Phospholipid

SL:

Sphingolipid

S1P:

Sphingosine-1-phosphate

TSH:

Thyroid-stimulating hormone

TSI:

Thyroid-stimulating immunoglobulin

T4:

Thyroxine

T3:

Triiodothyronine

UPLC:

Ultrahigh performance liquid chromatography

VLDL:

Very low-density lipoproteins

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Acknowledgments

This study was supported by a grant (NRF-2015R1A2A1A01004677 to M.H.M) from the National Research Foundation (NRF) of Korea, a grant (2014M3A9B6069341 to E.J.L) from the Bio & Medical Technology Development Program of NRF. S.K.B acknowledges the support of the Yonsei University Research Fund (Post Doc. Researcher Supporting Program) of 2016 (project no.: 2016-12-0230).

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Author notes

  1. Seul Kee Byeon and Se Hee Park contributed equally to this work.

Authors and Affiliations

  1. Department of Chemistry, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul, 03722, South Korea

    Seul Kee Byeon, Jong Cheol Lee & Myeong Hee Moon

  2. Division of Endocrinology and Metabolism, Department of Internal Medicine, National Health Insurance Service Ilsan Hospital, Goyang, Gyeonggi, 10444, South Korea

    Se Hee Park

  3. Graduate School, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, South Korea

    Se Hee Park & Eun Jig Lee

  4. Department of Internal Medicine, Chaum Life Center, CHA University School of Medicine, Seoul, 06062, South Korea

    Sena Hwang

  5. Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, South Korea

    Cheol Ryong Ku, Dong Yeob Shin & Eun Jig Lee

  6. Institute of Endocrine Research, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, South Korea

    Cheol Ryong Ku, Dong Yeob Shin & Eun Jig Lee

  7. Department of Ophthalmology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, South Korea

    Jin Sook Yoon

Authors
  1. Seul Kee Byeon
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  2. Se Hee Park
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  9. Myeong Hee Moon
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Contributions

Seul Kee Byeon performed lipidomic experiments, analyzed data, and wrote the manuscript with assistance from Jong Cheol Lee. Se Hee Park contributed to sample collection and data analysis, and wrote the manuscript. Sena Hwang collected samples and contributed to the study design. Cheol Ryong Ku, Dong Yeob Shin, and Jin Sook Yoon contributed to sample collection. Eun Jig Lee designed and supervised the study and contributed to sample collection. Myeong Hee Moon supervised lipidomic analysis and wrote the manuscript. All authors edited the paper.

Corresponding authors

Correspondence to Eun Jig Lee or Myeong Hee Moon.

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The authors declare that they have no conflict of interest.

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Byeon, S.K., Park, S.H., Lee, J.C. et al. Lipidomic differentiation of Graves’ ophthalmopathy in plasma and urine from Graves’ disease patients. Anal Bioanal Chem 410, 7121–7133 (2018). https://doi.org/10.1007/s00216-018-1313-2

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  • DOI: https://doi.org/10.1007/s00216-018-1313-2

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