Skip to main content
Erschienen in: Clinical Rheumatology 7/2020

13.02.2020 | Original Article

Comparison of cytokine profiles between anti-ARS antibody-positive interstitial lung diseases and those with anti-MDA-5 antibodies

verfasst von: Katsuaki Asakawa, Kazutaka Yoshizawa, Ami Aoki, Yosuke Kimura, Takahiro Tanaka, Kazumasa Ohashi, Masachika Hayashi, Toshiaki Kikuchi, Shinji Sato, Toshinori Takada

Erschienen in: Clinical Rheumatology | Ausgabe 7/2020

Einloggen, um Zugang zu erhalten

Abstract

Introduction/objectives

Interstitial lung disease (ILD) is a significant cause of mortality among patients with dermatomyositis (DM) or polymyositis (PM). There are two subtypes of PM and DM often complicated with ILD: those with anti-aminoacyl-tRNA synthetase (anti-ARS) antibodies and those with anti-MDA-5-associated amyopathic DM (ADM). Our aim is to clarify the inflammatory and immunological differences between the disorders.

Methods

We retrospectively collected consecutive patients with anti-ARS-ILD and those with anti-MDA-5 antibody-positive ADM-ILD. The serum concentration of 38 cytokines was measured using a cytokine panel. The relative risks for anti-MDA-5 antibody-positive ADM-ILD were examined with univariate and multivariate logistic regression models. Spearman’s rank correlation coefficient was calculated between cytokine levels and clinical parameters in the disease. Levels of cytokines were compared between anti-ARS-ILD and anti-MDA-5-positive ADM-ILD patients (alive or dead) using Dunnett’s test.

Results

Twenty-three patients with anti-ARS-ILD and the same number of patients with anti-MDA-5-positive ADM-ILD were enrolled. The anti-MDA-5 group had poor survival (p = 0.025). Univariate logistic regression models showed that eotaxin, IL-10, IP-10, and MCP-1 were associated with the diagnosis of anti-MDA-5-positive ADM-ILD. Multivariate logistic regression models revealed that IP-10 was the most significantly associated (p = 0.001). Relationship analyses showed that IL-10 had significant positive correlations with CK (r = 0.5267, p = 0.009) and ferritin (r = 0.4528, p = 0.045). A comparison of the cytokine levels found that IP-10 was elevated in both patients who were alive and patients who had died with ADM-ILD compared with the levels in those with ARS-ILD (p = 0.003 and p = 0.001, respectively).

Conclusions

Anti-MDA-5-positive ADM-ILD had poorer survival than anti-ARS-ILD. IP-10 seems to be most deeply involved in the pathophysiology of anti-MDA-5-associated ADM-ILD.
Key Points
To clarify differences in the inflammatory and immunological features of anti-MDA-5-positive ADM-ILD and anti-ARS-ILD, we performed an observational study to measure serum cytokine concentrations before treatment using a multiplex immunoassay system.
Multivariate logistic regression models revealed that IP-10 was associated with the most significant relative risk for ADM-ILD with anti-MDA-5 antibodies.
Levels of IP-10 were elevated considerably in anti-MDA-5-positive survivors and nonsurvivors compared with the levels in anti-ARS patients.
These results suggest that IP-10 is the most deeply involved in the pathophysiology of anti-MDA-5-positive ADM-ILD.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Bottai M, Tjarnlund A, Santoni G, Werth VP, Pilkington C, de Visser M, Alfredsson L, Amato AA, Barohn RJ, Liang MH, Singh JA, Aggarwal R, Arnardottir S, Chinoy H, Cooper RG, Danko K, Dimachkie MM, Feldman BM, Garcia-De La Torre I, Gordon P, Hayashi T, Katz JD, Kohsaka H, Lachenbruch PA, Lang BA, Li Y, Oddis CV, Olesinka M, Reed AM, Rutkowska-Sak L, Sanner H, Selva-O'Callaghan A, Wook Song Y, Vencovsky J, Ytterberg SR, Miller FW, Rider LG, Lundberg IE, International Myositis Classification Criteria Project consortium tEr, the Juvenile Dermatomyositis Cohort Biomarker S, Repository (2017) EULAR/ACR classification criteria for adult and juvenile idiopathic inflammatory myopathies and their major subgroups: a methodology report. RMD Open 3(2):e000507. https://doi.org/10.1136/rmdopen-2017-000507 CrossRefPubMedPubMedCentral Bottai M, Tjarnlund A, Santoni G, Werth VP, Pilkington C, de Visser M, Alfredsson L, Amato AA, Barohn RJ, Liang MH, Singh JA, Aggarwal R, Arnardottir S, Chinoy H, Cooper RG, Danko K, Dimachkie MM, Feldman BM, Garcia-De La Torre I, Gordon P, Hayashi T, Katz JD, Kohsaka H, Lachenbruch PA, Lang BA, Li Y, Oddis CV, Olesinka M, Reed AM, Rutkowska-Sak L, Sanner H, Selva-O'Callaghan A, Wook Song Y, Vencovsky J, Ytterberg SR, Miller FW, Rider LG, Lundberg IE, International Myositis Classification Criteria Project consortium tEr, the Juvenile Dermatomyositis Cohort Biomarker S, Repository (2017) EULAR/ACR classification criteria for adult and juvenile idiopathic inflammatory myopathies and their major subgroups: a methodology report. RMD Open 3(2):e000507. https://​doi.​org/​10.​1136/​rmdopen-2017-000507 CrossRefPubMedPubMedCentral
2.
Zurück zum Zitat Love LA, Leff RL, Fraser DD, Targoff IN, Dalakas M, Plotz PH, Miller FW (1991) A new approach to the classification of idiopathic inflammatory myopathy: myositis-specific autoantibodies define useful homogeneous patient groups. Medicine (Baltimore) 70(6):360–374CrossRef Love LA, Leff RL, Fraser DD, Targoff IN, Dalakas M, Plotz PH, Miller FW (1991) A new approach to the classification of idiopathic inflammatory myopathy: myositis-specific autoantibodies define useful homogeneous patient groups. Medicine (Baltimore) 70(6):360–374CrossRef
4.
Zurück zum Zitat Targoff IN (2008) Autoantibodies and their significance in myositis. Curr Rheumatol Rep 10(4):333–340CrossRef Targoff IN (2008) Autoantibodies and their significance in myositis. Curr Rheumatol Rep 10(4):333–340CrossRef
5.
Zurück zum Zitat Yura H, Sakamoto N, Satoh M, Ishimoto H, Hanaka T, Ito C, Hasegawa T, Tanaka S, Miyamura T, Nakashima S, Hara A, Kakugawa T, Oda K, Kido T, Obase Y, Ishimatsu Y, Yatera K, Kawakami A, Mukae H (2017) Clinical characteristics of patients with anti-aminoacyl-tRNA synthetase antibody positive idiopathic interstitial pneumonia. Respir Med 132:189–194. https://doi.org/10.1016/j.rmed.2017.10.020 CrossRefPubMed Yura H, Sakamoto N, Satoh M, Ishimoto H, Hanaka T, Ito C, Hasegawa T, Tanaka S, Miyamura T, Nakashima S, Hara A, Kakugawa T, Oda K, Kido T, Obase Y, Ishimatsu Y, Yatera K, Kawakami A, Mukae H (2017) Clinical characteristics of patients with anti-aminoacyl-tRNA synthetase antibody positive idiopathic interstitial pneumonia. Respir Med 132:189–194. https://​doi.​org/​10.​1016/​j.​rmed.​2017.​10.​020 CrossRefPubMed
6.
Zurück zum Zitat Tanizawa K, Handa T, Nakashima R, Kubo T, Hosono Y, Watanabe K, Aihara K, Ikezoe K, Sokai A, Nakatsuka Y, Taguchi Y, Hatta K, Noma S, Kobashi Y, Yoshizawa A, Oga T, Hirai T, Chin K, Nagai S, Izumi T, Mimori T, Mishima M (2017) The long-term outcome of interstitial lung disease with anti-aminoacyl-tRNA synthetase antibodies. Respir Med 127:57–64. https://doi.org/10.1016/j.rmed.2017.04.007 CrossRefPubMed Tanizawa K, Handa T, Nakashima R, Kubo T, Hosono Y, Watanabe K, Aihara K, Ikezoe K, Sokai A, Nakatsuka Y, Taguchi Y, Hatta K, Noma S, Kobashi Y, Yoshizawa A, Oga T, Hirai T, Chin K, Nagai S, Izumi T, Mimori T, Mishima M (2017) The long-term outcome of interstitial lung disease with anti-aminoacyl-tRNA synthetase antibodies. Respir Med 127:57–64. https://​doi.​org/​10.​1016/​j.​rmed.​2017.​04.​007 CrossRefPubMed
8.
Zurück zum Zitat Yoshida N, Okamoto M, Kaieda S, Fujimoto K, Ebata T, Tajiri M, Nakamura M, Tominaga M, Wakasugi D, Kawayama T, Kuwana M, Mimori T, Ida H, Hoshino T (2017) Association of anti-aminoacyl-transfer RNA synthetase antibody and anti-melanoma differentiation-associated gene 5 antibody with the therapeutic response of polymyositis/dermatomyositis-associated interstitial lung disease. Respir Investig 55(1):24–32. https://doi.org/10.1016/j.resinv.2016.08.007 CrossRefPubMed Yoshida N, Okamoto M, Kaieda S, Fujimoto K, Ebata T, Tajiri M, Nakamura M, Tominaga M, Wakasugi D, Kawayama T, Kuwana M, Mimori T, Ida H, Hoshino T (2017) Association of anti-aminoacyl-transfer RNA synthetase antibody and anti-melanoma differentiation-associated gene 5 antibody with the therapeutic response of polymyositis/dermatomyositis-associated interstitial lung disease. Respir Investig 55(1):24–32. https://​doi.​org/​10.​1016/​j.​resinv.​2016.​08.​007 CrossRefPubMed
10.
Zurück zum Zitat Li L, Wang Q, Wen X, Liu C, Wu C, Yang F, Zeng X, Li Y (2017) Assessment of anti-MDA5 antibody as a diagnostic biomarker in patients with dermatomyositis-associated interstitial lung disease or rapidly progressive interstitial lung disease. Oncotarget. https://doi.org/10.18632/oncotarget.19050 Li L, Wang Q, Wen X, Liu C, Wu C, Yang F, Zeng X, Li Y (2017) Assessment of anti-MDA5 antibody as a diagnostic biomarker in patients with dermatomyositis-associated interstitial lung disease or rapidly progressive interstitial lung disease. Oncotarget. https://​doi.​org/​10.​18632/​oncotarget.​19050
12.
Zurück zum Zitat Sato S, Hoshino K, Satoh T, Fujita T, Kawakami Y, Kuwana M (2009) RNA helicase encoded by melanoma differentiation-associated gene 5 is a major autoantigen in patients with clinically amyopathic dermatomyositis: association with rapidly progressive interstitial lung disease. Arthritis Rheum 60(7):2193–2200. https://doi.org/10.1002/art.24621 CrossRefPubMed Sato S, Hoshino K, Satoh T, Fujita T, Kawakami Y, Kuwana M (2009) RNA helicase encoded by melanoma differentiation-associated gene 5 is a major autoantigen in patients with clinically amyopathic dermatomyositis: association with rapidly progressive interstitial lung disease. Arthritis Rheum 60(7):2193–2200. https://​doi.​org/​10.​1002/​art.​24621 CrossRefPubMed
22.
Zurück zum Zitat Isoda K, Kotani T, Takeuchi T, Kiboshi T, Hata K, Ishida T, Otani K, Kamimori T, Fujiwara H, Shoda T, Makino S (2017) Comparison of long-term prognosis and relapse of dermatomyositis complicated with interstitial pneumonia according to autoantibodies: anti-aminoacyl tRNA synthetase antibodies versus anti-melanoma differentiation-associated gene 5 antibody. Rheumatol Int 37(8):1335–1340. https://doi.org/10.1007/s00296-017-3729-y CrossRefPubMed Isoda K, Kotani T, Takeuchi T, Kiboshi T, Hata K, Ishida T, Otani K, Kamimori T, Fujiwara H, Shoda T, Makino S (2017) Comparison of long-term prognosis and relapse of dermatomyositis complicated with interstitial pneumonia according to autoantibodies: anti-aminoacyl tRNA synthetase antibodies versus anti-melanoma differentiation-associated gene 5 antibody. Rheumatol Int 37(8):1335–1340. https://​doi.​org/​10.​1007/​s00296-017-3729-y CrossRefPubMed
24.
Zurück zum Zitat Gono T, Kaneko H, Kawaguchi Y, Hanaoka M, Kataoka S, Kuwana M, Takagi K, Ichida H, Katsumata Y, Ota Y, Kawasumi H, Yamanaka H (2014) Cytokine profiles in polymyositis and dermatomyositis complicated by rapidly progressive or chronic interstitial lung disease. Rheumatology (Oxford). https://doi.org/10.1093/rheumatology/keu258 Gono T, Kaneko H, Kawaguchi Y, Hanaoka M, Kataoka S, Kuwana M, Takagi K, Ichida H, Katsumata Y, Ota Y, Kawasumi H, Yamanaka H (2014) Cytokine profiles in polymyositis and dermatomyositis complicated by rapidly progressive or chronic interstitial lung disease. Rheumatology (Oxford). https://​doi.​org/​10.​1093/​rheumatology/​keu258
25.
Zurück zum Zitat Luster AD, Ravetch JV (1987) Biochemical characterization of a gamma interferon-inducible cytokine (IP-10). J Exp Med 166(4):1084–1097CrossRef Luster AD, Ravetch JV (1987) Biochemical characterization of a gamma interferon-inducible cytokine (IP-10). J Exp Med 166(4):1084–1097CrossRef
26.
Zurück zum Zitat Dhillon NK, Peng F, Ransohoff RM, Buch S (2007) PDGF synergistically enhances IFN-gamma-induced expression of CXCL10 in blood-derived macrophages: implications for HIV dementia. J Immunol 179(5):2722–2730CrossRef Dhillon NK, Peng F, Ransohoff RM, Buch S (2007) PDGF synergistically enhances IFN-gamma-induced expression of CXCL10 in blood-derived macrophages: implications for HIV dementia. J Immunol 179(5):2722–2730CrossRef
27.
Zurück zum Zitat Neville LF, Mathiak G, Bagasra O (1997) The immunobiology of interferon-gamma inducible protein 10 kD (IP-10): a novel, pleiotropic member of the C-X-C chemokine superfamily. Cytokine Growth Factor Rev 8(3):207–219CrossRef Neville LF, Mathiak G, Bagasra O (1997) The immunobiology of interferon-gamma inducible protein 10 kD (IP-10): a novel, pleiotropic member of the C-X-C chemokine superfamily. Cytokine Growth Factor Rev 8(3):207–219CrossRef
30.
Zurück zum Zitat Kawaguchi S, Sakuraba H, Haga T, Matsumiya T, Seya K, Endo T, Sawada N, Iino C, Kikuchi H, Hiraga H, Fukuda S, Imaizumi T (2019) Melanoma differentiation-associated gene 5 positively modulates TNF-alpha-induced CXCL10 expression in cultured HuH-7 and HLE cells. Inflammation 42(6):2095–2104. https://doi.org/10.1007/s10753-019-01073-3 CrossRefPubMed Kawaguchi S, Sakuraba H, Haga T, Matsumiya T, Seya K, Endo T, Sawada N, Iino C, Kikuchi H, Hiraga H, Fukuda S, Imaizumi T (2019) Melanoma differentiation-associated gene 5 positively modulates TNF-alpha-induced CXCL10 expression in cultured HuH-7 and HLE cells. Inflammation 42(6):2095–2104. https://​doi.​org/​10.​1007/​s10753-019-01073-3 CrossRefPubMed
31.
Zurück zum Zitat Baechler EC, Bauer JW, Slattery CA, Ortmann WA, Espe KJ, Novitzke J, Ytterberg SR, Gregersen PK, Behrens TW, Reed AM (2007) An interferon signature in the peripheral blood of dermatomyositis patients is associated with disease activity. Molecular medicine (Cambridge, Mass) 13(1–2):59–68. https://doi.org/10.2119/2006-00085.Baechler CrossRef Baechler EC, Bauer JW, Slattery CA, Ortmann WA, Espe KJ, Novitzke J, Ytterberg SR, Gregersen PK, Behrens TW, Reed AM (2007) An interferon signature in the peripheral blood of dermatomyositis patients is associated with disease activity. Molecular medicine (Cambridge, Mass) 13(1–2):59–68. https://​doi.​org/​10.​2119/​2006-00085.​Baechler CrossRef
32.
Zurück zum Zitat Bilgic H, Ytterberg SR, Amin S, McNallan KT, Wilson JC, Koeuth T, Ellingson S, Newman B, Bauer JW, Peterson EJ, Baechler EC, Reed AM (2009) Interleukin-6 and type I interferon-regulated genes and chemokines mark disease activity in dermatomyositis. Arthritis Rheum 60(11):3436–3446. https://doi.org/10.1002/art.24936 CrossRefPubMed Bilgic H, Ytterberg SR, Amin S, McNallan KT, Wilson JC, Koeuth T, Ellingson S, Newman B, Bauer JW, Peterson EJ, Baechler EC, Reed AM (2009) Interleukin-6 and type I interferon-regulated genes and chemokines mark disease activity in dermatomyositis. Arthritis Rheum 60(11):3436–3446. https://​doi.​org/​10.​1002/​art.​24936 CrossRefPubMed
Metadaten
Titel
Comparison of cytokine profiles between anti-ARS antibody-positive interstitial lung diseases and those with anti-MDA-5 antibodies
verfasst von
Katsuaki Asakawa
Kazutaka Yoshizawa
Ami Aoki
Yosuke Kimura
Takahiro Tanaka
Kazumasa Ohashi
Masachika Hayashi
Toshiaki Kikuchi
Shinji Sato
Toshinori Takada
Publikationsdatum
13.02.2020
Verlag
Springer London
Erschienen in
Clinical Rheumatology / Ausgabe 7/2020
Print ISSN: 0770-3198
Elektronische ISSN: 1434-9949
DOI
https://doi.org/10.1007/s10067-020-04984-x

Weitere Artikel der Ausgabe 7/2020

Clinical Rheumatology 7/2020 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Notfall-TEP der Hüfte ist auch bei 90-Jährigen machbar

26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Bei schweren Reaktionen auf Insektenstiche empfiehlt sich eine spezifische Immuntherapie

Insektenstiche sind bei Erwachsenen die häufigsten Auslöser einer Anaphylaxie. Einen wirksamen Schutz vor schweren anaphylaktischen Reaktionen bietet die allergenspezifische Immuntherapie. Jedoch kommt sie noch viel zu selten zum Einsatz.

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

25.04.2024 Hypertonie Nachrichten

Beginnen ältere Männer im Pflegeheim eine Antihypertensiva-Therapie, dann ist die Frakturrate in den folgenden 30 Tagen mehr als verdoppelt. Besonders häufig stürzen Demenzkranke und Männer, die erstmals Blutdrucksenker nehmen. Dafür spricht eine Analyse unter US-Veteranen.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.