Additional Hydroxychloroquine Therapy Regulates Adipokines in Systemic Lupus Erythematosus with Stable Disease Activity

Risa Wakiya¹, Kiyo Ueeda¹, Hiromi Shimada¹, Shusaku Nakashima¹, Mikiya Kato¹, Taichi Miyagi², Mansour mai¹, Koichi Sugihara¹, Rina Semba¹, Mao Mizusaki¹, Tomohiro Kameda¹ and Hiroaki Dobashi³, ¹Kagawa University, Takamatsu, Japan, ²Kagawa University, Kidagun, Japan, ³Department of Internal Medicine, Division of Hematology, Rheumatology and Respiratory Medicine, Faculty of Medicine, Kagawa University, Kagawa, Japan

Meeting: ACR Convergence 2021

Keywords: Adipokines, cytokines, Hydroxychloroquine, resistin, Systemic lupus erythematosus (SLE)

Session Information

Date: Tuesday, November 9, 2021

Title: SLE – Treatment Poster (1732–1772)

Session Type: Poster Session D

Session Time: 8:30AM-10:30AM

Background/Purpose: In systemic lupus erythematosus (SLE), atherosclerosis is strongly associated with vital prognosis. On the other hand, arteriosclerosis is strongly influenced by serum adipokines. The effect on serum adipokine by hydroxychloroquine (HCQ) therapy, which has a vital prognostic benefit in systemic lupus erythematosus, has not been fully investigated. The purpose of this study is to determine the effect of HCQ treatment on serum adipokines in SLE.

Methods: To determine the effect of HCQ treatment alone on serum adipokines, SLE patients with stable disease activity who had not previously received HCQ treatment were included in the study. Additional HCQ therapy was started in these patients from 2016 to 2020. Disease activity was assessed by SLEDAI, CLASI and LLDAS and serum complement titers, anti-ds-DNA antibodies. Serum adipokines (adiponectin, resistin and leptin) were analyzed using ELISA kit (Adiponectin/Acrp30 Quantikine ELISA Kit, R＆D and Simple Plex, ProteinSimple) before and 3 months after starting additional HCQ treatment.

In addition, we measured serum cytokines (TNF-α, IL-6, IL-8, MCP-1, MIP-1a, IL-1ra, IL-2) reported to be associated with the pathogenesis of SLE using multiplex immunoassay (Luminex Assay, R＆D) and analyzed the relationship with changes of serum adipokines.

Results: Forty-one patients (4 males, 37 females, mean age 41.3±13.2 years) without changing treatment regimens, including glucocorticoids and immunosuppressive drugs other than HCQ were included (Table 1).

Serum adiponectin levels were significantly increased and serum resistin levels were significantly decreased 3 months after additional HCQ administration compared to baseline. No significant changes were observed in serum leptin levels (Fig. 1).

Regarding the association between these adipokines and disease activity parameters, changes of these adipokines by HCQ treatment were not associated with those of hypocomplement. However, change of leptin alone were positively correlated with decreasing anti-dsDNA antibodies.

On the other hand, additional HCQ administration decreased serum TNF-α, IL-6, IL-1ra and IL-2 levels significantly 3 months after compared to baseline.

Regarding the association between these cytokines change and disease activity, the change of TNF-α levels were related to improvement of hypocomplementemia (C3 and C4). Furthermore, the reduction of IL-1ra by additional HCQ treatment was associated with the achievement of LLDAS .

Among of these adipokines, change of resistin was correlated with reduction of TNF-α or IL-1ra by HCQ therapy significantly (Fig. 2). However, the increasing adiponectin was not correlated with change of these cytokines.

Conclusion: HCQ treatment could regulate serum adipocytokine in SLE patients. Resistin was modulated through the effect of HCQ on disease activity. However, the effect of HCQ on serum adiponectin was suggested to be independent on change of disease activity parameters or several cytokines associated with SLE disease activity.

Table 1. Characteristics of SLE patients enrolled in this study Anti-dsDNA positive means anti ds-DNA titer increases over 12 IU/ml Low complement means any of C3, C4 and CH50 decreases to less 68mg/dl, less 12mg/dl, 30U/ml. APS: Anti-phospholipid antibody syndrome, NPSLE: neuropsychiatric SLE, LLDAS: lupus low disease activity state.

Fig. 1 Serum adipockine levels before and after HCQ treatment. Serum levels of the indicated cytokines and factors were measured before or after 3 months (3M Post) treatment (Tx) with HCQ. Colored lines represent individual patients. NS: not significant. P values were determined by the Wilcoxon signed-rank test

Fig. 2 Association between changes in serum cytokines and resistin after HCQ treatment. Reduction of resistin was correlated with reduction of TNF-α or IL_1ra by HCQ therapy significantly. P values were determined by univariate analysis. r: correlation coefficient.

Disclosures: R. Wakiya, None; K. Ueeda, None; H. Shimada, None; S. Nakashima, None; M. Kato, None; T. Miyagi, None; M. mai, None; K. Sugihara, None; R. Semba, None; M. Mizusaki, None; T. Kameda, None; H. Dobashi, None.

To cite this abstract in AMA style:

Wakiya R, Ueeda K, Shimada H, Nakashima S, Kato M, Miyagi T, mai M, Sugihara K, Semba R, Mizusaki M, Kameda T, Dobashi H. Additional Hydroxychloroquine Therapy Regulates Adipokines in Systemic Lupus Erythematosus with Stable Disease Activity [abstract]. Arthritis Rheumatol. 2021; 73 (suppl 9). https://acrabstracts.org/abstract/additional-hydroxychloroquine-therapy-regulates-adipokines-in-systemic-lupus-erythematosus-with-stable-disease-activity/. Accessed .

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