title: Immunogenicity and Lupus-Like Autoantibody Production Can Be Linked to Each Other along With Type I Interferon Production in Patients with Rheumatoid Arthritis Treated With Infliximab: A Retrospective Study of a Single Center Cohort.
abstract: Besides anti-drug antibodies, anti-nuclear antibodies and anti-DNA antibodies are often induced in patients with rheumatoid arthritis treated with tumor necrosis factor inhibitors. We examined the association between immunogenicity, autoantibody production, and serum cytokine profiles in patients with rheumatoid arthritis treated with infliximab. Japanese patients with rheumatoid arthritis (n = 57) were retrospectively examined. Serum trough levels of infliximab, anti-drug antibody, anti-nuclear antibody, and anti-DNA (Farr), anti-single-stranded DNA and anti-double-stranded DNA antibodies were measured. Interleukin-6, interferon-γ, interferon-α, and B-cell activating factor levels were also measured in the same sera. Then, we validated the association between anti-drug antibody and these serum markers along with clinical response to infliximab. Anti-drug antibodies developed in twenty-one patients (36.8%), whose serum trough levels of infliximab were significantly lower than those in anti-drug antibody-negative patients (0.09 ± 0.03 vs. 2.48 ± 0.326 μg/mL, p < 0.0001). There were no significant differences in clinical backgrounds between the two groups. The anti-drug antibody-positive patients were more likely to develop anti-nuclear antibody titers of ≥ ×160 compared to the negative patients (14 to 57% vs. 17 to 33%). In addition, anti-DNA antibodies (Farr) (from 1.5 ± 0.4 to 35 ± 17 IU/mL, p = 0.0001), especially IgM-anti-double stranded DNA antibody (from 5.1 ± 0.7 to 41 ± 8.9 IU/mL, p < 0.0001), and IgG-anti-single stranded DNA antibody (from 13 ± 1.1 to 35 ± 13, p = 0.0145) were significantly increased in anti-drug antibody-positive but not in negative patients. Moreover, the anti-drug antibody-positive, but not the negative patients, showed significant increased levels of interferon-α (from 248.7 ± 102.3 to 466.8 ± 135.1 pg/mL, p = 0.0353) and B-cell activating factor (from 1073 ± 75.1 to 1387 ± 136.5 pg/mL, p = 0.0208) following infliximab treatment. The development of anti-drug antibody against infliximab and lupus-like autoantibody production in patients with rheumatoid arthritis treated with infliximab can be linked each other along with increased lupus-associated cytokine levels including type I interferons.
authors.affiliation: Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Ishikawa
authors.affiliation: Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Fujii
authors.affiliation: Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Seiko Kondo
authors.initials: SK
authors.lastname: Ishikawa
authors.affiliation: Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Naoichiro
authors.initials: N
authors.lastname: Yukawa
authors.affiliation: Department of the Control for Rheumatic Diseases, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Motomu
authors.initials: M
authors.lastname: Hashimoto
authors.affiliation: Department of the Control for Rheumatic Diseases, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Moritoshi
authors.initials: M
authors.lastname: Furu
authors.affiliation: Department of Orthopedic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Hiromu
authors.initials: H
authors.lastname: Ito
authors.affiliation: Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Ohmura
authors.affiliation: Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Tsuneyo
authors.initials: T
authors.lastname: Mimori
mesh_terms: D000328:Adult; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D001323:Autoantibodies / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007370:Interferon Type I / Q000096:biosynthesis*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies
chemical_list: D001323:Autoantibodies; D007370:Interferon Type I