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Increased Serum B Cell Activating Factor and a Proliferation-inducing Ligand Are Associated with Interstitial Lung Disease in Patients with Juvenile Dermatomyositis.
J Rheumatol 2015; 42(12):2412-8JR

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.

CONCLUSION

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+Show Affiliations

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.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.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.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.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.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.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.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.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.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26472413

Citation

Kobayashi, Norimoto, et al. "Increased Serum B Cell Activating Factor and a Proliferation-inducing Ligand Are Associated With Interstitial Lung Disease in Patients With Juvenile Dermatomyositis." The Journal of Rheumatology, vol. 42, no. 12, 2015, pp. 2412-8.
Kobayashi N, Kobayashi I, Mori M, et al. Increased Serum B Cell Activating Factor and a Proliferation-inducing Ligand Are Associated with Interstitial Lung Disease in Patients with Juvenile Dermatomyositis. J Rheumatol. 2015;42(12):2412-8.
Kobayashi, N., Kobayashi, I., Mori, M., Sato, S., Iwata, N., Shigemura, T., ... Koike, K. (2015). Increased Serum B Cell Activating Factor and a Proliferation-inducing Ligand Are Associated with Interstitial Lung Disease in Patients with Juvenile Dermatomyositis. The Journal of Rheumatology, 42(12), pp. 2412-8. doi:10.3899/jrheum.140977.
Kobayashi N, et al. Increased Serum B Cell Activating Factor and a Proliferation-inducing Ligand Are Associated With Interstitial Lung Disease in Patients With Juvenile Dermatomyositis. J Rheumatol. 2015;42(12):2412-8. PubMed PMID: 26472413.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Increased Serum B Cell Activating Factor and a Proliferation-inducing Ligand Are Associated with Interstitial Lung Disease in Patients with Juvenile Dermatomyositis. AU - Kobayashi,Norimoto, AU - Kobayashi,Ichiro, AU - Mori,Masaaki, AU - Sato,Shinji, AU - Iwata,Naomi, AU - Shigemura,Tomonari, AU - Agematsu,Kazunaga, AU - Yokota,Shumpei, AU - Koike,Kenichi, Y1 - 2015/10/15/ PY - 2015/07/23/accepted PY - 2015/10/17/entrez PY - 2015/10/17/pubmed PY - 2016/9/15/medline KW - ANTI-MDA5 KW - B CELL ACTIVATING FACTOR KW - INTERSTITIAL LUNG DISEASE KW - JUVENILE DERMATOMYOSITIS KW - PROLIFERATION-INDUCING LIGAND SP - 2412 EP - 8 JF - The Journal of rheumatology JO - J. Rheumatol. VL - 42 IS - 12 N2 - 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. CONCLUSION: 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. SN - 0315-162X UR - https://www.unboundmedicine.com/medline/citation/26472413/Increased_Serum_B_Cell_Activating_Factor_and_a_Proliferation_inducing_Ligand_Are_Associated_with_Interstitial_Lung_Disease_in_Patients_with_Juvenile_Dermatomyositis_ L2 - http://www.jrheum.org/cgi/pmidlookup?view=long&amp;pmid=26472413 DB - PRIME DP - Unbound Medicine ER -