Pos0427 Seasonal Variations of Type I Interferon Activity in Patients With Systemic Lupus Erythematosus

Background: Ultraviolet (UV) radiation has been identified as a risk factor for disease onset and flares in patients with systemic lupus erythematosus (SLE). Excessive production of type I interferon (IFN), particularly IFN-κ, occurs locally in the skin of patients with SLE, and is considered to contribute to the exacerbation of cutaneous manifestations induced by UV radiation [1]. UV exposure has also been implicated not only in exposed skin areas but also in the worsening of non-exposed skin areas and other organs [2]. In addition, an increase in circulating type I IFN, especially IFN-α, has been identified as an independent risk factor for lupus flares [3]. However, the impact of UV radiation on circulating type I IFN activity in patients with SLE, as well as its seasonal variation and involvement in disease flares, remains largely unclear. Objectives: This study aimed to investigate the influence of UV radiation intensity on circulating type I IFN activity and disease flares in SLE patients. Methods: A prospective longitudinal study was conducted over one year in patients fulfilling the 1997 revised ACR classification criteria for SLE. Patients were monitored every three months for one year, and clinical information, medications, and disease activity were collected. Serum type I IFN activity was measured at each time point by WISH bioassay [4]. Serial serum samples were also collected from healthy controls, and type I IFN activity was compared with SLE patients over time. Evaluation data were excluded from the analysis if patients had experienced an infection within two weeks or vaccination within one month preceding the evaluation date. Results: Data from 505 points were collected from 168 patients with SLE. The study population consisted of 89.3% females, with a mean age of 44.8 years, mean disease duration of 13.1 years, median SELENA-SLEDAI score of 2, and median prednisolone dose of 5 mg/day. Of the patients, 57.1% were administered hydroxychloroquine (HCQ). Serum type I IFN activity was higher in July and August with elevated UV radiation. When assessed seasonally, serum type I IFN activity during summer (June - August) was significantly higher than that during spring (March - May) and autumn (September - November), and tended to be higher than that during winter (December - February) (p=0.0487, p=0.0434, and p=0.0687, respectively) (Figure 1A). In the HCQ-treated group, serum type I IFN activity showed a consistently lower trend throughout the year than that in the non-HCQ-treated group (Figure 1B). During the observation period, 56% of patients achieved lupus low disease activity state (LLDAS) at least once. Even in those patients, serum type I IFN activity remained significantly higher than that in healthy controls (median IFN score: HC 0.0 vs. SLE 2.4, p<0.0001). Among the patients who achieved LLDAS, there was no significant difference in serum IFN activity based on HCQ use. Serum type I IFN activity did not show any seasonal variation in healthy controls. Owing to the limited number of observed flares (7/168 patients) and the relatively low disease activities of the study participants, a thorough examination of the association between serum IFN activity, treatment regimens, and flares could not be adequately conducted. Conclusion: Serum IFN activity in patients with SLE showed seasonal variations, which were specifically positively linked to UV radiation intensity. In the HCQ-treated group, serum type I IFN activity was consistently and longitudinally suppressed compared with that in the non-HCQ-treated group. REFERENCES: [1] Sarkar MK, et al. Ann Rheum Dis. 2018;77:1653-64. [2] Schmidt E, et al. Ann NY Acad Sci. 2007;1108:35-40. [3] Hoffman RW, et al. Arthritis Rheumatol. 2017;69:634-54. [4] Niewold TB, et al. Genes Immun. 2007;8:492-502. Acknowledgements: NIL. Disclosure of Interests: Kazusa Miyachi: None declared, Taro Iwamoto AstraZeneca and GlaxoSmithKline, Shotaro Kojima: None declared, Tomoaki Ida: None declared, Masahiro Yasui: None declared, Daiki Nakagomi: None declared, Ayako Matsuki: None declared, Shin-Ichiro Kagami Janssen Pharmaceutical, AbbbVie Inc, VIATRIS, Nippon Boehringer Ingelheim Co., Ltd, AstraZeneca K.K, Novartis Pharma K. K, Takeda Pharmaceutical Co., Ltd, Chugai Pharmaceutical Co., Ltd., Asahi Kasei Pharma Corporation, Yoshihisa Kobayashi: None declared, Tomohiro Tamachi: None declared, Michio Fujiwara Astellas Pharma, Asahi Kasei Phaema, Hirotoshi Kawashima: None declared, Yoshihiro Oya: None declared, Yoshie Sanayama: None declared, Shunsuke Furuta Asahi Kasei Pharma, Eisai, Daiichi Sankyo, Chugai Pharmaceutical and Kissei Pharma, Asahi Kasei Pharma, Kei Ikeda Abbvie, Eli Lilly Japan, and AstraZeneca, Mitsubishi-Tanabe Pharma, Hiroshi Nakajima Chugai Pharmaceutical, Abbvie, Takeda Pharmaceutical, Astellas Pharma, Eli Lilly Japan, Asahi Kasei Pharma, Janssen Pharmaceutical, Mitsubishi Tanabe Pharma, Eisai, Bristol Myers Squibb, and Nippon Kayaku, Chugai Pharmaceutical, Abbvie, Takeda Pharmaceutical, Astellas Pharma, Eli Lilly Japan, Asahi Kasei Pharma, Pfizer Japan, UCB Japan, Eizai, Mitsubishi Tanabe Pharma, and Bristol Myers Squibb.