Effect of Additional Administration of HCQ on Pro-inflammatory Cytokine Expression, Especially in Lupus Nephritis

Risa Wakiya¹, Kiyo Ueeda ², Hiromi Shimada ², Shusaku Nakashima ¹, Mai Mahmoud Fahmy Mansour ¹, Mikiya Kato ¹, Taichi Miyagi ¹, Tomohiro Kameda ¹ and Hiroaki Dobashi ², ¹Kagawa University, Kagawa, ²Kagawa University, Kagawa, Japan

Meeting: 2019 ACR/ARP Annual Meeting

Keywords: Hydroxychloroquine, il-8 and MRP8, Lupus nephritis, Systemic lupus erythematosus (SLE)

Session Information

Date: Tuesday, November 12, 2019

Title: SLE – Clinical Poster III: Treatment

Session Type: Poster Session (Tuesday)

Session Time: 9:00AM-11:00AM

Background/Purpose: Hydroxychloroquine(HCQ) is recommended for all patients with SLE in EULAR recommendation 2019, however, there are not enough data about the effect of additional HCQ treatment on the expression of pro-inflammatory cytokines, which plays an important role in SLE pathogenesis. The aim of this study is to clarify the effect of additional HCQ treatment on pro-inflammatory cytokines in SLE patients with low disease activity(LDA).

Methods: All patients with LDA enrolled in this study started HCQ treatment and had been receiving oral HCQ continuously for at least 3 months without using other immunosuppressive treatments or glucocorticoids. LDA was defined as SELENA-SLEDAI score of 8 or less with no activity in major organ systems and current prednisolone or equivalent dose of 10mg per day or less and well-tolerated maintenance doses of immunosuppressant. Serum levels of IFN-α, MRP8, MRP14, TNF-α, IL-2, IL-6, IL-8, VEGF-A, MCP-1, MIP-1α, IL-1β, IL-1ra, and G-CSF were measured at the time of HCQ administration and 3 months later using ELISA (CircuLex ELISA Kit, MBL)(Human IFN-alpha ELISA Kit, R＆D) or a multiplex immunoassay (Luminex Assay, R＆D). Data was analyzed using JMP® 13 software (SAS Institute Inc., Cary, NC, USA).

Results: 42 patients were enrolled in this study (M:F; 4:38, average age; 41.3±13.3; Table 1). 19 cases were in sustained remission of lupus nephritis(LN) patients. Serum levels of MRP8, MRP14 and IL-1ra at baseline were significantly higher in patients with a history of LN compared with those without LN (p=0.012, p=0.0043 and p=0.0092, respectively). Serum levels of MRP8, MRP14, TNF-α, IL-6, VEGF-A, IL-1ra, and IL-2 decreased significantly 3 months after additional HCQ treatment. The expressions of IFN-α didn’t decrease significantly in 9 cases that could be detected.
Serum levels of IL-8 and MIP-1a decreased 3 months after additional HCQ treatment, but the difference was not statistically significant (p=0.211, p=0.109). However, serum levels of IL-8 same as VEGF-A significantly decreased in patients with a history of LN (with LN: IL-8, p=0.0026; VEGF-A, p=0.048; without LN: IL-8, p=0.370; VEGF-A, p=0.284). In addition, the magnitude of the changes in serum IL-8 levels in patients with a history of LN was significantly higher than in those without a history of LN (p=0.0039; Figure 1). The changes of IL-8 levels were correlated with those of serum MRP8 (r=0.32, p=0.049, Figure2).

Conclusion: Additional HCQ treatment could decrease the several pro-inflammatory cytokines expression in SLE patients with LDA, especially in LN. Additionally, our data indicates that the effect of additional HCQ treatment could reduce the IL-8 expression in remission LN subjects significantly, which is reported to be associated with improvement of LN prognosis. HCQ use should be considered to be prescribed for all SLE patients as described in EULAR recommendation 2019.

Table 1. Characteristics of SLE patients enrolled in this study
*1 Two patients received multiple immunosuppressants.
*2 Four patients received antiplatelet agent and anticoagulant agent.
*3 Anti-dsDNA positive means anti ds-DNA titer increases over 12 IU/ml.
*4 Low complement means any of C3, C4 and CH50 decreases to less 68mg/dl, less 12mg/dl, less 30U/ml.

Figure 1.The magnitude of changes in serum IL-8 levels in patients with a history of LN were significantly higher than in patients without a history of LN. For statistical analyses * p<0.05, NS: Not significant, P value: Steel-Dwass test

Figure 2. Correlation between the changes of IL-8 and those of MRP8 -r=0.32 p<0.05-.

Disclosure: R. Wakiya, None; K. Ueeda, None; H. Shimada, None; S. Nakashima, None; M. Mahmoud Fahmy Mansour, None; M. Kato, None; T. Miyagi, None; T. Kameda, None; H. Dobashi, None.

To cite this abstract in AMA style:

Wakiya R, Ueeda K, Shimada H, Nakashima S, Mahmoud Fahmy Mansour M, Kato M, Miyagi T, Kameda T, Dobashi H. Effect of Additional Administration of HCQ on Pro-inflammatory Cytokine Expression, Especially in Lupus Nephritis [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/effect-of-additional-administration-of-hcq-on-pro-inflammatory-cytokine-expression-especially-in-lupus-nephritis/. Accessed .

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