AB0042 CYTOKINE NETWORK ELUCIDATED BY THE QUANTIFICATION OF MULTIPLE CYTOKINES IN THE SERUM SEQUENTIALLY SAMPLED FROM RA PATIENTS WHO WERE TREATED WITH BIOLOGIC DMARDS
Authors: K. Sato, S. Mamada, C. Hayashi, T. Nagashima, S. Minota
Journal: Annals of the Rheumatic Diseases (2020)

Background: Biologic disease modifying anti-rheumatic drugs (DMARDs) have demonstrated that proinflammatory cytokines such as interleukin (IL-) 6 and tumor necrosis factor (TNF) play important roles in the pathogenesis of rheumatoid arthritis (RA). Other cytokines, such as type I interferons (IFNs), are also implicated in its pathogenesis (ref 1). However, the complete picture of the cytokine network involved in RA remains to be elucidated. Objectives: By quantifying sets of cytokines in the serum of RA patients before and after treatment with various biologic DMARDs, we sought to determine the effects of drugs on (A) type I IFNs, (B) soluble IL-6 receptors, and (C) other cytokines. Methods: 52 patients with RA were treated with various biologic DMARDs (tocilizumab (TOC): 16, abatacept (ABT): 15, and TNF inhibitors (TNFi): 21). Serum samples were obtained (1) before, (2) approximately 4 weeks after (3) and approximately 12 weeks after the initiation of treatment. A suspension bead-array system was used for analysis; Bio-Plex Human Cytokine 17-plex Assay kits and Express Custom Panels (Bio-Rad), including IFN-β, IFN-α2, soluble IL-6 receptor α (sIL6Rα) and gp130 were used. Results: (1) As expected, the disease activity score 28-joiny count (DAS28) using the erythrocyte sedimentation rate (ESR) significantly decreased in all three groups (TOC, ABT and TNFi) by 12 weeks. (2) IFN-α2 was barely detected in the serum samples. IFN-β seemed to increase slightly in the ABT group, but the increase was not statistically significant. (3) The levels of sIL6Rα did not change substantially. Those of gp130 decreased slightly but significantly in the TOC group by 12 weeks. (4) The levels of IL-6 decreased significantly in the ABT group by 12 weeks. Those in the TNFi group decreased significantly at 4 weeks but not 12 weeks (Fig. 1A). (5) The levels of IL-7 decreased significantly only in the TOC group (Fig. 1B). Conclusion: (1) The biologic DMARDs tested in this study did not significantly affect the serum levels of type I IFNs in this study. (2) The decrease in gp130 in the TOC group may imply that gp130 is induced by IL-6, although whether this level of decrease has physiological significance is open to question. (3) Serum IL-6 was significantly decreased in the TNFi group at 4 weeks but not 12 weeks. TNF has been reported to induce IL-6 (ref 2), but negative feedback loop(s) may be present. Such a feedback system might make the discontinuation of TNFi difficult, even if patients are in remission. (4) IL-7 may be a target of IL-6. A higher level of IL-7 has been reported to be present in the joints of RA patients compared with osteoarthrosis and it is a cytokine implicated in the differentiation of osteoclasts (ref 3). This may partly explain the effect of TOC on preventing bone erosion in RA. References: [1]Ann Rheum Dis. 2007; 66: 1008–14 [2]Rheumatology 2007; 46: 920-6 [3]Rheumatology 2008; 47: 753-9 Acknowledgments: We thank all the members of the Division of Rheumatology and Clinical Immunology, Department of Medicine, Jichi Medical University. We are also grateful to the patients involved in this study. Disclosure of Interests: Kojiro Sato Grant/research support from: Abbie, Pfizer, Chugai, Astellas, Mitsubishi-Tanabe, Ono, Takeda, Sachiko Mamada: None declared, Chiyomi Hayashi: None declared, Takao Nagashima: None declared, Seiji Minota: None declared