Elsevier

Clinica Chimica Acta

Volume 503, April 2020, Pages 99-106
Clinica Chimica Acta

Elevated phosphatidylserine-specific phospholipase A1 level in hyperthyroidism

https://doi.org/10.1016/j.cca.2020.01.011Get rights and content

Highlights

  • The serum PS-PLA1 levels were higher in hyperthyroidism such as Graves’ disease.

  • The serum PS-PLA1 levels were strongly correlated with thyroid hormones.

  • The serum PS-PLA1 levels were lowered by treatment with anti-thyroid reagents.

  • The changes in PS-PLA1 were strongly correlated with those in thyroid hormones.

  • PS-PLA1 might be useful as a supplementary diagnostic test for thyroid function.

Abstract

Objectives

Although a single nucleotide polymorphism in a specific receptor for lysophosphatidylserine, a lysophospholipid mediator involved in the immune system, is reportedly associated with Graves’ disease, the association between lysophosphatidylserine and thyroid disorders remains to be elucidated. Therefore, we aimed to investigate the association between the level of phosphatidylserine-specific phospholipase A1 (PS-PLA1), which produces lysophosphatidylserine, and thyroid disorders.

Methods

We measured serum PS-PLA1 levels in the patients with various thyroid disorders (n = 120) and normal subjects (n = 58).

Results

We observed that the serum PS-PLA1 levels were higher in the subjects with Graves’ disease, subacute thyroiditis, or silent thyroiditis, while they were not modulated in the patients with hypothyroidism. The serum PS-PLA1 levels were strongly correlated with the levels of thyroid hormones, especially in the subjects with Graves’ disease. Moreover, we found that the serum PS-PLA1 levels were lowered by treatment with anti-thyroid reagents in subjects with Graves’ disease and that the changes in PS-PLA1 were strongly correlated with those in thyroid hormones.

Conclusion

These results suggest that PS-PLA1 might be a novel target in the treatment of hyperthyroidism, especially Graves’ disease, and that its measurement might be useful as a supplementary diagnostic test for thyroid function.

Introduction

Lysophosphatidylserine (LysoPS) is a novel bioactive lipid that structurally belongs to the family of glycero-lysophospholipids, which includes lysophosphatidic acid (LPA)—a well-studied lipid mediator. LysoPS is emerging as an attractive therapeutic target, since specific G-protein coupled receptors have been identified for LysoPS, G protein-coupled receptor 34 (Gpr34, LPS1), P2Y receptor family member 10 (P2Y10, LPS2), and G protein-coupled receptor 174 (GPR174, LPS3); however, the physiological properties of LysoPS have not been fully elucidated [1], [2]. Regarding the association between LysoPS and human diseases, we previously measured LysoPS levels in human plasma samples using liquid chromatography-mass spectrometry and/or measurements of phosphatidylserine-specific phospholipase A1 (PS-PLA1), one of the enzymes that produces LysoPS, in samples of blood and ascites and revealed that LysoPS and PS-PLA1 might be associated with acute coronary syndrome [3], [4], [5] and cancer [6], [7].

In addition to the measurement of LysoPS and PS-PLA1 levels in clinical samples, several groups have attempted to investigate the involvement of LysoPS in human diseases through genomic studies, such as analyses of single nucleotide polymorphisms (SNPs). Several reports have demonstrated that SNPs of GPR174, one of the LysoPS receptors, are associated with Graves’ disease [8], [9], [10], [11]. At present, the mechanisms responsible for the association between GPR174 and Graves’ disease remain to be elucidated. Nevertheless, LysoPS is emerging as a novel lipid mediator that modulates immune systems, and LysoPS reportedly suppresses several immunological responses in T cells and macrophages [12], [13], [14], [15], [16], [17]. Since immunological disturbances are involved in the pathogenesis of Graves’ disease [18], these emerging physiological properties of LysoPS prompted us to investigate the association between LysoPS and Graves’ disease. Although the direct measurement of plasma LysoPS levels in subjects with Graves’ disease would be optimal, the LysoPS level can be elevated to a great extent by platelet activation during sampling [4], [19]. Therefore, in this study, we measured the serum PS-PLA1 levels, which are stable in serum samples, in patients with various thyroid diseases as well as healthy subjects.

Section snippets

Subjects

We collected serum samples from 58 healthy adult volunteers who had provided written informed consent and 42 subjects with untreated Graves’ disease, 17 subjects with Graves’ disease who were receiving treatment with anti-thyroid drugs, 18 subjects with untreated subacute thyroiditis, 9 subjects with untreated silent thyroiditis, 6 subjects with untreated Plummer’s disease, 9 subjects with untreated Hashimoto’s thyroiditis, 12 subjects with treated Hashimoto’s thyroiditis, and 7 subjects who

Serum PS-PLA1 levels were higher in the subjects with hyperthyroidism

First, we compared the serum PS-PLA1 levels among healthy subjects, subjects with hyperthyroidism (subjects with Graves’ disease, subacute thyroiditis, silent thyroiditis, or Plummer’s disease), and subjects with hypothyroidism (subjects with Hashimoto’s thyroiditis or who had undergone a total thyroidectomy but had not received thyroid hormone supplementation). As shown in Fig. 1, the serum PS-PLA1 levels were higher in the subjects with untreated Graves’ disease, subacute thyroiditis, and

Discussion

In the present study, we measured the serum PS-PLA1 levels in subjects with various thyroid diseases and aimed to elucidate the association between the PS-PLA1 level and Graves’ disease. Although the serum PS-PLA1 level was higher in the subjects with Graves’ disease, an elevation in the PS-PLA1 level was also observed in subjects with subacute thyroiditis and silent thyroiditis, suggesting that PS-PLA1 might be involved in the pathogenesis of inflammation in the thyroid, which is a process

Conclusion

In summary, the serum PS-PLA1 levels were higher in the subjects with hyperthyroidism. PS-PLA1 might be a novel target for the treatment of hyperthyroidism, especially Graves’ disease, and the measurement of the PS-PLA1 level might be useful as a supplementary diagnostic test for evaluating thyroid function.

CRediT authorship contribution statement

Kazuki Nakawatari: Formal analysis, Investigation, Methodology, Writing - original draft. Makoto Kurano: Conceptualization, Formal analysis, Investigation, Writing - review & editing, Supervision, Project administration, Funding acquisition. Osamu Araki: Investigation. Masako Nishikawa: Investigation, Validation. Satoshi Shimamoto: Resources, Investigation. Koji Igarashi: Conceptualization, Resources, Investigation. Junken Aoki: Conceptualization, Funding acquisition. Masami Murakami:

Acknowledgements

This work was supported by CREST and LEAP from AMED, a Grant-in-Aid for Scientific Research on Innovative Areas 15H05906 (Y.Y.), and JSPS KAKENHI Grant Number 16H06236 (M.K.)

Disclosure

K.I. and S. S. are employees of TOSOH Corporation.

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