title: Increased Serum B Cell Activating Factor and a Proliferation-inducing Ligand Are Associated with Interstitial Lung Disease in Patients with Juvenile Dermatomyositis.
abstract: OBJECTIVE
  Rapidly progressive interstitial lung disease (RP-ILD) is an intractable and fatal complication of juvenile dermatomyositis (JDM). This study evaluated serum levels of B cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) in JDM patients with complicating ILD, and their association with ILD phenotypes, clinical variables, and anti-melanoma differentiation-associated gene 5 (MDA5).
  
  
  METHODS
  We measured the levels of BAFF, APRIL, and anti-MDA5 in the sera of 23 JDM patients with ILD [8 in the RP-ILD group and 15 in the chronic ILD (C-ILD) group], 17 JDM patients without ILD (non-ILD group), and 10 age-matched controls, using the ELISA method. ILD was identified by high-resolution computed tomography.
  
  
  RESULTS
  Serum BAFF titers were significantly higher in the JDM patients with RP-ILD versus those with C-ILD (p = 0.011) and in healthy controls (p = 0.0004). The C-ILD group had significantly higher levels of BAFF versus controls (p ≤ 0.0001). Serum APRIL was markedly elevated in the RP-ILD group as compared with the C-ILD group (p = 0.003) and controls (p = 0.006). In patients with ILD, both BAFF and APRIL levels were correlated with serum Krebs von den Lungen-6 and interleukin 18. Subjects with high titer anti-MDA5 (> 200 U) had higher levels of BAFF and APRIL than those with low titer anti-MDA5 (< 100 U; p = 0.019 and p = 0.0029, respectively), which may have been due to a relationship between RP-ILD and high anti-MDA5 titer.
  
  
  CONCLUSIONS
  Our findings of markedly elevated levels of BAFF and APRIL in patients with RP-ILD JDM suggest the potential importance of these cytokines in the diagnosis and treatment of RP-ILD accompanying JDM.
authors.affiliation: From the Department of Pediatrics, and Department of Infection and Host Defense, Graduate School of Medicine, Shinshu University School of Medicine, Matsumoto; Department of Pediatrics, Hokkaido University Graduate School of Medicine, Sapporo; Department of Pediatrics, Yokohama City University Graduate School of Medicine, Yokohama; Department of Rheumatology, Tokai University School of Medicine, Isehara; Department of Immunology and Infectious Diseases, Aichi Children's Health and Medical Center, Ohbu, Japan.N. Kobayashi, MD, PhD, Department of Pediatrics, Shinshu University School of Medicine; I. Kobayashi, MD, PhD, Department of Pediatrics, Hokkaido University Graduate School of Medicine; M. Mori, MD, PhD, Department of Pediatrics, Yokohama City University Graduate School of Medicine; S. Sato, MD, PhD, Department of Rheumatology, Tokai University School of Medicine; N. Iwata, MD, Department of Immunology and Infectious Diseases, Aichi Children's Health and Medical Center; T. Shigemura, MD, PhD, Department of Pediatrics, Shinshu University School of Medicine; K. Agematsu, MD, PhD, Department of Infection and Host Defense, Graduate School of Medicine, Shinshu University; S. Yokota, MD, PhD, Department of Pediatrics, Yokohama City University Graduate School of Medicine; K. Koike, MD, PhD, Department of Pediatrics, Shinshu University School of Medicine. norimoto@shinshu-u.ac.jp.
authors.forename: Norimoto
authors.initials: N
authors.lastname: Kobayashi
authors.affiliation: From the Department of Pediatrics, and Department of Infection and Host Defense, Graduate School of Medicine, Shinshu University School of Medicine, Matsumoto; Department of Pediatrics, Hokkaido University Graduate School of Medicine, Sapporo; Department of Pediatrics, Yokohama City University Graduate School of Medicine, Yokohama; Department of Rheumatology, Tokai University School of Medicine, Isehara; Department of Immunology and Infectious Diseases, Aichi Children's Health and Medical Center, Ohbu, Japan.N. Kobayashi, MD, PhD, Department of Pediatrics, Shinshu University School of Medicine; I. Kobayashi, MD, PhD, Department of Pediatrics, Hokkaido University Graduate School of Medicine; M. Mori, MD, PhD, Department of Pediatrics, Yokohama City University Graduate School of Medicine; S. Sato, MD, PhD, Department of Rheumatology, Tokai University School of Medicine; N. Iwata, MD, Department of Immunology and Infectious Diseases, Aichi Children's Health and Medical Center; T. Shigemura, MD, PhD, Department of Pediatrics, Shinshu University School of Medicine; K. Agematsu, MD, PhD, Department of Infection and Host Defense, Graduate School of Medicine, Shinshu University; S. Yokota, MD, PhD, Department of Pediatrics, Yokohama City University Graduate School of Medicine; K. Koike, MD, PhD, Department of Pediatrics, Shinshu University School of Medicine.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kobayashi
authors.affiliation: From the Department of Pediatrics, and Department of Infection and Host Defense, Graduate School of Medicine, Shinshu University School of Medicine, Matsumoto; Department of Pediatrics, Hokkaido University Graduate School of Medicine, Sapporo; Department of Pediatrics, Yokohama City University Graduate School of Medicine, Yokohama; Department of Rheumatology, Tokai University School of Medicine, Isehara; Department of Immunology and Infectious Diseases, Aichi Children's Health and Medical Center, Ohbu, Japan.N. Kobayashi, MD, PhD, Department of Pediatrics, Shinshu University School of Medicine; I. Kobayashi, MD, PhD, Department of Pediatrics, Hokkaido University Graduate School of Medicine; M. Mori, MD, PhD, Department of Pediatrics, Yokohama City University Graduate School of Medicine; S. Sato, MD, PhD, Department of Rheumatology, Tokai University School of Medicine; N. Iwata, MD, Department of Immunology and Infectious Diseases, Aichi Children's Health and Medical Center; T. Shigemura, MD, PhD, Department of Pediatrics, Shinshu University School of Medicine; K. Agematsu, MD, PhD, Department of Infection and Host Defense, Graduate School of Medicine, Shinshu University; S. Yokota, MD, PhD, Department of Pediatrics, Yokohama City University Graduate School of Medicine; K. Koike, MD, PhD, Department of Pediatrics, Shinshu University School of Medicine.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Mori
authors.affiliation: From the Department of Pediatrics, and Department of Infection and Host Defense, Graduate School of Medicine, Shinshu University School of Medicine, Matsumoto; Department of Pediatrics, Hokkaido University Graduate School of Medicine, Sapporo; Department of Pediatrics, Yokohama City University Graduate School of Medicine, Yokohama; Department of Rheumatology, Tokai University School of Medicine, Isehara; Department of Immunology and Infectious Diseases, Aichi Children's Health and Medical Center, Ohbu, Japan.N. Kobayashi, MD, PhD, Department of Pediatrics, Shinshu University School of Medicine; I. Kobayashi, MD, PhD, Department of Pediatrics, Hokkaido University Graduate School of Medicine; M. Mori, MD, PhD, Department of Pediatrics, Yokohama City University Graduate School of Medicine; S. Sato, MD, PhD, Department of Rheumatology, Tokai University School of Medicine; N. Iwata, MD, Department of Immunology and Infectious Diseases, Aichi Children's Health and Medical Center; T. Shigemura, MD, PhD, Department of Pediatrics, Shinshu University School of Medicine; K. Agematsu, MD, PhD, Department of Infection and Host Defense, Graduate School of Medicine, Shinshu University; S. Yokota, MD, PhD, Department of Pediatrics, Yokohama City University Graduate School of Medicine; K. Koike, MD, PhD, Department of Pediatrics, Shinshu University School of Medicine.
authors.forename: Shinji
authors.initials: S
authors.lastname: Sato
authors.affiliation: From the Department of Pediatrics, and Department of Infection and Host Defense, Graduate School of Medicine, Shinshu University School of Medicine, Matsumoto; Department of Pediatrics, Hokkaido University Graduate School of Medicine, Sapporo; Department of Pediatrics, Yokohama City University Graduate School of Medicine, Yokohama; Department of Rheumatology, Tokai University School of Medicine, Isehara; Department of Immunology and Infectious Diseases, Aichi Children's Health and Medical Center, Ohbu, Japan.N. Kobayashi, MD, PhD, Department of Pediatrics, Shinshu University School of Medicine; I. Kobayashi, MD, PhD, Department of Pediatrics, Hokkaido University Graduate School of Medicine; M. Mori, MD, PhD, Department of Pediatrics, Yokohama City University Graduate School of Medicine; S. Sato, MD, PhD, Department of Rheumatology, Tokai University School of Medicine; N. Iwata, MD, Department of Immunology and Infectious Diseases, Aichi Children's Health and Medical Center; T. Shigemura, MD, PhD, Department of Pediatrics, Shinshu University School of Medicine; K. Agematsu, MD, PhD, Department of Infection and Host Defense, Graduate School of Medicine, Shinshu University; S. Yokota, MD, PhD, Department of Pediatrics, Yokohama City University Graduate School of Medicine; K. Koike, MD, PhD, Department of Pediatrics, Shinshu University School of Medicine.
authors.forename: Naomi
authors.initials: N
authors.lastname: Iwata
authors.affiliation: From the Department of Pediatrics, and Department of Infection and Host Defense, Graduate School of Medicine, Shinshu University School of Medicine, Matsumoto; Department of Pediatrics, Hokkaido University Graduate School of Medicine, Sapporo; Department of Pediatrics, Yokohama City University Graduate School of Medicine, Yokohama; Department of Rheumatology, Tokai University School of Medicine, Isehara; Department of Immunology and Infectious Diseases, Aichi Children's Health and Medical Center, Ohbu, Japan.N. Kobayashi, MD, PhD, Department of Pediatrics, Shinshu University School of Medicine; I. Kobayashi, MD, PhD, Department of Pediatrics, Hokkaido University Graduate School of Medicine; M. Mori, MD, PhD, Department of Pediatrics, Yokohama City University Graduate School of Medicine; S. Sato, MD, PhD, Department of Rheumatology, Tokai University School of Medicine; N. Iwata, MD, Department of Immunology and Infectious Diseases, Aichi Children's Health and Medical Center; T. Shigemura, MD, PhD, Department of Pediatrics, Shinshu University School of Medicine; K. Agematsu, MD, PhD, Department of Infection and Host Defense, Graduate School of Medicine, Shinshu University; S. Yokota, MD, PhD, Department of Pediatrics, Yokohama City University Graduate School of Medicine; K. Koike, MD, PhD, Department of Pediatrics, Shinshu University School of Medicine.
authors.forename: Tomonari
authors.initials: T
authors.lastname: Shigemura
authors.affiliation: From the Department of Pediatrics, and Department of Infection and Host Defense, Graduate School of Medicine, Shinshu University School of Medicine, Matsumoto; Department of Pediatrics, Hokkaido University Graduate School of Medicine, Sapporo; Department of Pediatrics, Yokohama City University Graduate School of Medicine, Yokohama; Department of Rheumatology, Tokai University School of Medicine, Isehara; Department of Immunology and Infectious Diseases, Aichi Children's Health and Medical Center, Ohbu, Japan.N. Kobayashi, MD, PhD, Department of Pediatrics, Shinshu University School of Medicine; I. Kobayashi, MD, PhD, Department of Pediatrics, Hokkaido University Graduate School of Medicine; M. Mori, MD, PhD, Department of Pediatrics, Yokohama City University Graduate School of Medicine; S. Sato, MD, PhD, Department of Rheumatology, Tokai University School of Medicine; N. Iwata, MD, Department of Immunology and Infectious Diseases, Aichi Children's Health and Medical Center; T. Shigemura, MD, PhD, Department of Pediatrics, Shinshu University School of Medicine; K. Agematsu, MD, PhD, Department of Infection and Host Defense, Graduate School of Medicine, Shinshu University; S. Yokota, MD, PhD, Department of Pediatrics, Yokohama City University Graduate School of Medicine; K. Koike, MD, PhD, Department of Pediatrics, Shinshu University School of Medicine.
authors.forename: Kazunaga
authors.initials: K
authors.lastname: Agematsu
authors.affiliation: From the Department of Pediatrics, and Department of Infection and Host Defense, Graduate School of Medicine, Shinshu University School of Medicine, Matsumoto; Department of Pediatrics, Hokkaido University Graduate School of Medicine, Sapporo; Department of Pediatrics, Yokohama City University Graduate School of Medicine, Yokohama; Department of Rheumatology, Tokai University School of Medicine, Isehara; Department of Immunology and Infectious Diseases, Aichi Children's Health and Medical Center, Ohbu, Japan.N. Kobayashi, MD, PhD, Department of Pediatrics, Shinshu University School of Medicine; I. Kobayashi, MD, PhD, Department of Pediatrics, Hokkaido University Graduate School of Medicine; M. Mori, MD, PhD, Department of Pediatrics, Yokohama City University Graduate School of Medicine; S. Sato, MD, PhD, Department of Rheumatology, Tokai University School of Medicine; N. Iwata, MD, Department of Immunology and Infectious Diseases, Aichi Children's Health and Medical Center; T. Shigemura, MD, PhD, Department of Pediatrics, Shinshu University School of Medicine; K. Agematsu, MD, PhD, Department of Infection and Host Defense, Graduate School of Medicine, Shinshu University; S. Yokota, MD, PhD, Department of Pediatrics, Yokohama City University Graduate School of Medicine; K. Koike, MD, PhD, Department of Pediatrics, Shinshu University School of Medicine.
authors.forename: Shumpei
authors.initials: S
authors.lastname: Yokota
authors.affiliation: From the Department of Pediatrics, and Department of Infection and Host Defense, Graduate School of Medicine, Shinshu University School of Medicine, Matsumoto; Department of Pediatrics, Hokkaido University Graduate School of Medicine, Sapporo; Department of Pediatrics, Yokohama City University Graduate School of Medicine, Yokohama; Department of Rheumatology, Tokai University School of Medicine, Isehara; Department of Immunology and Infectious Diseases, Aichi Children's Health and Medical Center, Ohbu, Japan.N. Kobayashi, MD, PhD, Department of Pediatrics, Shinshu University School of Medicine; I. Kobayashi, MD, PhD, Department of Pediatrics, Hokkaido University Graduate School of Medicine; M. Mori, MD, PhD, Department of Pediatrics, Yokohama City University Graduate School of Medicine; S. Sato, MD, PhD, Department of Rheumatology, Tokai University School of Medicine; N. Iwata, MD, Department of Immunology and Infectious Diseases, Aichi Children's Health and Medical Center; T. Shigemura, MD, PhD, Department of Pediatrics, Shinshu University School of Medicine; K. Agematsu, MD, PhD, Department of Infection and Host Defense, Graduate School of Medicine, Shinshu University; S. Yokota, MD, PhD, Department of Pediatrics, Yokohama City University Graduate School of Medicine; K. Koike, MD, PhD, Department of Pediatrics, Shinshu University School of Medicine.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Koike
mesh_terms: D053264:B-Cell Activating Factor / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D015897:Comorbidity; D003882:Dermatomyositis / Q000097:blood* / Q000453:epidemiology* / Q000503:physiopathology; D018450:Disease Progression; D005260:Female; D006785:Hospitals, University; D006801:Humans; D007564:Japan; D017563:Lung Diseases, Interstitial / Q000097:blood* / Q000453:epidemiology* / Q000503:physiopathology; D008297:Male; D011237:Predictive Value of Tests; D011379:Prognosis; D012016:Reference Values; D018570:Risk Assessment; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000097:blood*
chemical_list: D053264:B-Cell Activating Factor; D015415:Biomarkers; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13
keywords: ANTI-MDA5; B CELL ACTIVATING FACTOR; INTERSTITIAL LUNG DISEASE; JUVENILE DERMATOMYOSITIS; PROLIFERATION-INDUCING LIGAND