title: Predictors of clinical outcomes in patients with neuropsychiatric systemic lupus erythematosus.
abstract: BACKGROUND
  Neuropsychiatric systemic lupus erythematosus (NPSLE), a serious organ disorder with a variety of symptoms, has diverse therapeutic outcomes because of the variability of NPSLE manifestations. A comprehensive association study of NPSLE among clinical and immunopathogenic aspects and outcomes has not been conducted.
  
  
  METHODS
  We analyzed the laboratory data, NPSLE symptoms, and clinical outcomes at 1yr post-treatment and the profiles of 27 cytokines, chemokines and growth factors in cerebrospinal fluid (CSF) samples using the Bio-Plex Human 27-plex panel from 28 NPSLE patients. Univariate and multivariable competing risks regression analyses were used to determine the predictive factors of clinical response. We also tried to predict the outcome of NPSLE by the 27 cytokines/chemokines/growth factors using a weighted-voting (WV) algorithm.
  
  
  RESULTS
  Of the two males and 26 females (92.9%), 16 were non-responders at 1yr post-treatment; in the final model, the independent predictors of non-responders were longer disease durations of SLE (odds ratio [OR]: 1.490, 95% confidence interval [CI]: 1.143-2.461, p=0.0003) and patients with more than one NPSLE symptom types (OR: 15.14, 95% CI: 1.227-452.1, p=0.0334). The pretreatment CSF interleukin (IL)-6, IL-10, interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) levels were significantly higher in the non-responders (p=0.0207, p=0.0054, p=0.0242 and p=0.0077, respectively). We identified six "minimum predictive markers:" IL-10, TNF-α, IL-6, IFN-γ, IL-4 and IL-13 by a WV algorithm that showed the highest accuracy (70.83%) and highest Matthews correlation coefficient (54.23%).
  
  
  CONCLUSIONS
  We have devised a numerical prediction scoring system that was able to separate the non-responders from responders. The patients with longer disease durations of SLE and those with more than one NPSLE symptom types had poorer outcomes. Our findings may indicate both the importance of making a diagnosis at an earlier phase for better therapeutic response and the usefulness of measuring multiple cytokines to predict NPSLE therapeutic outcomes.
authors.affiliation: Department of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan. Electronic address: kichinos@nagasaki-u.ac.jp.
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Ichinose
authors.affiliation: Department of Public Health, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Arima
authors.affiliation: Department of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Umeda
authors.affiliation: Department of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Shoichi
authors.initials: S
authors.lastname: Fukui
authors.affiliation: Department of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Nishino
authors.affiliation: Department of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Nakashima
authors.affiliation: Department of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Takahisa
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Department of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Horai
authors.affiliation: Department of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Koga
authors.affiliation: Department of Public Health, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Shin-Ya
authors.initials: SY
authors.lastname: Kawashiri
authors.affiliation: Department of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Iwamoto
authors.affiliation: Department of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Keita
authors.initials: K
authors.lastname: Fujikawa
authors.affiliation: Department of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Aramaki
authors.affiliation: Department of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Mami
authors.initials: M
authors.lastname: Tamai
authors.affiliation: Department of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Nakamura
authors.affiliation: Department of Clinical Research Center, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Shuntaro
authors.initials: S
authors.lastname: Sato
authors.affiliation: Department of Rehabilitation Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Origuchi
authors.affiliation: Department of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kawakami
mesh_terms: D000328:Adult; D000465:Algorithms; D015415:Biomarkers / Q000134:cerebrospinal fluid; D016207:Cytokines / Q000134:cerebrospinal fluid*; D005260:Female; D006801:Humans; D020945:Lupus Vasculitis, Central Nervous System / Q000175:diagnosis* / Q000188:drug therapy*; D008297:Male; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D016207:Cytokines
keywords: Cerebrospinal fluid; Multiple cytokine profiles; Neuropsychiatric systemic lupus erythematosus; Systemic lupus erythematosus; Weighted-voting algorithm