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Supplemental hydroxychloroquine therapy regulates adipokines in patients with systemic lupus erythematosus with stable disease

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Abstract

Background

In patients with systemic lupus erythematosus (SLE), a higher frequency of atherosclerotic lesions is associated with poor prognosis. Hydroxychloroquine (HCQ) has been reported to improve the lifespan and the prognosis of dyslipidaemia in patients with SLE, but the mechanism is unclear. We investigated the effect of supplemental HCQ treatment on the levels of serum cytokines associated with atherosclerosis in patients with stable SLE.

Methods

Patients with SLE who received supplemental HCQ and maintained low disease activity between January 2016 and September 2020 were included in this study. Disease activity was assessed using Safety of Estrogens in Lupus National Assessment-SLE Disease Activity Index, Cutaneous Lupus Erythematous Disease Area and Severity Index, and Lupus Low Disease Activity State. Serum complement titres, anti-dsDNA antibodies, and serum cytokines (adiponectin, resistin, and leptin) were analyzed before and after HCQ treatment.

Results

Forty-one patients (4 males and 37 females, mean age 41.3 ± 13.2 years) were included. Serum adiponectin levels were significantly increased after 3 months of HCQ treatment compared to baseline, and serum resistin levels were significantly reduced. The change in serum resistin level after HCQ administration was correlated with a significant reduction in serum TNF-α, interleukin (IL)-6, IL-8, and IL-1RA levels.

Conclusions

Supplemental HCQ treatment in patients with SLE improved adipokine levels. HCQ may improve prognosis by controlling disease activity in SLE and reducing risk factors for atherosclerosis.

Key Points

• Hydroxychloroquine has been reported to improve the prognosis of dyslipidaemia in patients with SLE, but the underlying mechanism is unclear.

• In this study, hydroxychloroquine improved adipokine levels in patients with SLE, implicating adipokines as a potential mechanism underlying the benefit of hydroxychloroquine on dyslipidaemia.

• Supplemental hydroxychloroquine should be considered in patients with SLE harboring lipid abnormalities and risk factors for atherosclerosis.

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Data availability

The dataset supporting the conclusions of this article is available upon reasonable request.

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Acknowledgements

We thank Enago (https://www.enago.jp) for editing a draft of this manuscript.

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Authors and Affiliations

  1. Division of Hematology, Rheumatology and Respiratory Medicine, Department of Internal Medicine, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa, 761-0793, Japan

    Risa Wakiya, Kiyo Ueeda, Hiromi Shimada, Shusaku Nakashima, Tomohiro Kameda, Mikiya Kato, Taichi Miyagi, Koichi Sugihara, Mao Mizusaki, Rina Mino, Norimitsu Kadowaki & Hiroaki Dobashi

  2. Department of Hygiene, Faculty of Medicine, Kagawa University, Kagawa, Japan

    Nobuyuki Miyatake

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  1. Risa Wakiya
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Contributions

All authors were involved in drafting the article or revising it critically for important intellectual content, and all authors approved the final version to be submitted for publication. RW and HD planned the study and wrote the manuscript. RW conducted the study and interpreted the results together with KU, SN, HS, TK, NM, MK, TM, KS, MM, RM, and HD. RW and NM conducted statistical analysis of the data obtained in the study. HD and NK reviewed the manuscript for intellectual content. The authors read and approved the final manuscript.

Corresponding author

Correspondence to Risa Wakiya.

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This study was approved by the ethical committee of Kagawa University (Heisei30-047) and was prospectively registered. All participants gave written informed consent prior to entering the study. The study was conducted in accordance with the Declaration of Helsinki.

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Wakiya, R., Ueeda, K., Shimada, H. et al. Supplemental hydroxychloroquine therapy regulates adipokines in patients with systemic lupus erythematosus with stable disease. Clin Rheumatol 41, 3345–3353 (2022). https://doi.org/10.1007/s10067-022-06282-0

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