IL-15 is a biomarker involved in the development of rapidly progressive interstitial lung disease complicated with polymyositis/dermatomyositis.
anti-MDA5 antibody
biomarkers
dermatomyositis
interleukin-15
polymyositis
rapidly progressive interstitial lung disease
Journal
Journal of internal medicine
ISSN: 1365-2796
Titre abrégé: J Intern Med
Pays: England
ID NLM: 8904841
Informations de publication
Date de publication:
02 2021
02 2021
Historique:
received:
21
04
2020
revised:
28
06
2020
accepted:
29
06
2020
pubmed:
22
7
2020
medline:
4
9
2021
entrez:
22
7
2020
Statut:
ppublish
Résumé
Polymyositis/dermatomyositis (PM/DM) is an autoimmune disease that is sometimes complicated with rapidly progressive interstitial lung disease (RPILD). However, serum and lung biomarkers that can predict RPILD development remain unclear. To determine potential serum and lung biomarkers that can predict RPILD development in patients with PM/DM-ILD. In total, 49 patients with PM/DM-ILD were enrolled. We measured the serum levels of 41 cytokines/chemokines, ferritin and anti-MDA5 antibody, compared them between the RPILD (n = 23) and non-RPILD (n = 26) groups, and ranked them by their importance through random forest analysis. To distinguish the two groups, we determined biomarker combinations by logistic regression analysis. We also measured the bronchoalveolar lavage fluid (BALF) levels of 41 cytokines/chemokines. Using immunohistochemistry, we examined IL-15 expression in lung tissues. The IL-15 production was also investigated using A549 and BEAS-2B cells. The RPILD group had significantly higher IL-15, IL-1RA, IL-6, CXCL10, VCAM-1, anti-MDA5 antibody and ferritin serum levels than the non-RPILD group, but it had a significantly low CCL22 level. Meanwhile, anti-MDA5 antibody, IL-15, CXCL8, CCL22, IL-1RA and ferritin were the best combination to distinguish the two groups. IL-15 and CCL22 were also predictive marker for RPILD development in anti-MDA5 antibody-positive patients. Additionally, the RPILD group had significantly high IL-15 levels in BALF. The lung tissues expressed IL-15, which increased after cytokine stimulation in the A549 cells. This study identified a combination of biomarkers predicting PM/DM-RPILD progression, and IL-15 is an important cytokine for predicting RPILD development and reflecting ILD severity.
Sections du résumé
BACKGROUND
Polymyositis/dermatomyositis (PM/DM) is an autoimmune disease that is sometimes complicated with rapidly progressive interstitial lung disease (RPILD). However, serum and lung biomarkers that can predict RPILD development remain unclear.
OBJECTIVES
To determine potential serum and lung biomarkers that can predict RPILD development in patients with PM/DM-ILD.
METHODS
In total, 49 patients with PM/DM-ILD were enrolled. We measured the serum levels of 41 cytokines/chemokines, ferritin and anti-MDA5 antibody, compared them between the RPILD (n = 23) and non-RPILD (n = 26) groups, and ranked them by their importance through random forest analysis. To distinguish the two groups, we determined biomarker combinations by logistic regression analysis. We also measured the bronchoalveolar lavage fluid (BALF) levels of 41 cytokines/chemokines. Using immunohistochemistry, we examined IL-15 expression in lung tissues. The IL-15 production was also investigated using A549 and BEAS-2B cells.
RESULTS
The RPILD group had significantly higher IL-15, IL-1RA, IL-6, CXCL10, VCAM-1, anti-MDA5 antibody and ferritin serum levels than the non-RPILD group, but it had a significantly low CCL22 level. Meanwhile, anti-MDA5 antibody, IL-15, CXCL8, CCL22, IL-1RA and ferritin were the best combination to distinguish the two groups. IL-15 and CCL22 were also predictive marker for RPILD development in anti-MDA5 antibody-positive patients. Additionally, the RPILD group had significantly high IL-15 levels in BALF. The lung tissues expressed IL-15, which increased after cytokine stimulation in the A549 cells.
CONCLUSION
This study identified a combination of biomarkers predicting PM/DM-RPILD progression, and IL-15 is an important cytokine for predicting RPILD development and reflecting ILD severity.
Substances chimiques
Biomarkers
0
Chemokines
0
Cytokines
0
Interleukin-15
0
Ferritins
9007-73-2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
206-220Informations de copyright
© 2020 The Association for the Publication of the Journal of Internal Medicine.
Références
Dalakas MC, Hohlfeld R. Polymyositis and dermatomyositis. Lancet 2003; 362: 971-82.
Fujikawa K, Kawakami A, Kaji K et al. Association of distinct clinical subsets with myositis-specific autoantibodies towards anti-155/140-kDa polypeptides, anti-140-kDa polypeptides, and anti-aminoacyl tRNA synthetases in Japanese patients with dermatomyositis: a single-centre, cross-sectional study. Scand J Rheumatol 2009; 38: 263-7.
Koga T, Fujikawa K, Horai Y et al. The diagnostic utility of anti-melanoma differentiation-associated gene 5 antibody testing for predicting the prognosis of Japanese patients with DM. Rheumatology 2012; 51: 1278-84.
Tsuji H, Nakashima R, Hosono Y et al. Multicenter prospective study of the efficacy and safety of combined immunosuppressive therapy with high-dose glucocorticoid, tacrolimus, and cyclophosphamide in interstitial lung diseases accompanied by anti-melanoma differentiation-associated gene 5-positive dermatomyositis. Arthritis Rheumatol 2020; 72: 488-98.
Matsuda KM, Yoshizaki A, Kuzumi A et al. Combined immunosuppressive therapy provides favorable prognosis and increased risk of cytomegalovirus reactivation in anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis. J Dermatol 2020; 47: 483-9.
Fujiki Y, Kotani T, Isoda K et al. Evaluation of clinical prognostic factors for interstitial pneumonia in anti-MDA5 antibody-positive dermatomyositis patients. Mod Rheumatol 2018; 28: 133-40.
Gono T, Sato S, Kawaguchi Y et al. Anti-MDA5 antibody, ferritin and IL-18 are useful for the evaluation of response to treatment in interstitial lung disease with anti-MDA5 antibody-positive dermatomyositis. Rheumatology 2012; 51: 1563-70.
Gono T, Kawaguchi Y, Hara M et al. Increased ferritin predicts development and severity of acute interstitial lung disease as a complication of dermatomyositis. Rheumatology 2010; 49: 1354-60.
Kawasumi H, Gono T, Kawaguchi Y et al. IL-6, IL-8, and IL-10 are associated with hyperferritinemia in rapidly progressive interstitial lung disease with polymyositis/dermatomyositis. Biomed Res Int 2014; 2014: 815245.
Bohan A, Peter JB. Polymyositis and dermatomyositis (first of two parts). N Engl J Med 1975; 292: 344-7.
Bohan A, Peter JB. Polymyositis and dermatomyositis (second of two parts). N Engl J Med 1975; 292: 403-7.
Lundberg IE, Tjarnlund A, Bottai M et al. 2017 European League Against Rheumatism/American College of Rheumatology classification criteria for adult and juvenile idiopathic inflammatory myopathies and their major subgroups. Ann Rheum Dis 2017; 76: 1955-64.
Sontheimer RD. Would a new name hasten the acceptance of amyopathic dermatomyositis (dermatomyositis sine myositis) as a distinctive subset within the idiopathic inflammatory dermatomyopathies spectrum of clinical illness? J Am Acad Dermatol 2002; 46: 626-36.
Gerami P, Schope JM, McDonald L, Walling HW, Sontheimer RD. A systematic review of adult-onset clinically amyopathic dermatomyositis (dermatomyositis sine myositis): a missing link within the spectrum of the idiopathic inflammatory myopathies. J Am Acad Dermatol 2006; 54: 597-613.
American Thoracic Society. Idiopathic pulmonary fibrosis: diagnosis and treatment. International consensus statement. American Thoracic Society (ATS), and the European Respiratory Society (ERS). Am J Respir Crit Care Med 2000; 161: 646-64.
Sakamoto N, Mukae H, Fujii T et al. Soluble form of Fas and Fas ligand in serum and bronchoalveolar lavage fluid of individuals infected with human T-lymphotropic virus type 1. Respir Med 2004; 98: 213-9.
Koga T, Migita K, Sato S et al. Multiple serum cytokine profiling to identify combinational diagnostic biomarkers in attacks of familial Mediterranean fever. Medicine 2016; 95: e3449.
Sato S, Hirakata M, Kuwana M et al. Autoantibodies to a 140-kd polypeptide, CADM-140, in Japanese patients with clinically amyopathic dermatomyositis. Arthritis Rheum 2005; 52: 1571-6.
Sato S, Hoshino K, Satoh T et al. 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 2009; 60: 2193-200.
Abe Y, Matsushita M, Tada K, Yamaji K, Takasaki Y, Tamura N. Clinical characteristics and change in the antibody titres of patients with anti-MDA5 antibody-positive inflammatory myositis. Rheumatology 2017; 56: 1492-7.
Chen M, Quan C, Diao L et al. Measurement of cytokines and chemokines and association with clinical severity of dermatomyositis and clinically amyopathic dermatomyositis. Br J Dermatol 2018; 179: 1334-41.
Ishikawa Y, Iwata S, Hanami K et al. Relevance of interferon-gamma in pathogenesis of life-threatening rapidly progressive interstitial lung disease in patients with dermatomyositis. Arthritis Res Ther 2018; 20: 240.
Dayer JM. From supernatants to cytokines: a personal view on the early history of IL-1, IL-1Ra, TNF and its inhibitor in rheumatology. Arthritis Res Ther 2018; 20: 101.
Burne MJ, Elghandour A, Haq M et al. IL-1 and TNF independent pathways mediate ICAM-1/VCAM-1 up-regulation in ischemia reperfusion injury. J Leukoc Biol 2001; 70: 192-8.
Patidar M, Yadav N, Dalai SK. Interleukin 15: A key cytokine for immunotherapy. Cytokine Growth Factor Rev 2016; 31: 49-59.
Jabri B, Abadie V. IL-15 functions as a danger signal to regulate tissue-resident T cells and tissue destruction. Nat Rev Immunol 2015; 15: 771-83.
Suzuki J, Morimoto S, Amano H, Tokano Y, Takasaki Y, Hashimoto H. Serum levels of interleukin 15 in patients with rheumatic diseases. J Rheumatol 2001; 28: 2389-91.
Okamoto M, Kato S, Oizumi K et al. Interleukin 18 (IL-18) in synergy with IL-2 induces lethal lung injury in mice: a potential role for cytokines, chemokines, and natural killer cells in the pathogenesis of interstitial pneumonia. Blood 2002; 99: 1289-98.
Takada T, Ohashi K, Hayashi M et al. Role of IL-15 in interstitial lung diseases in amyopathic dermatomyositis with anti-MDA-5 antibody. Respir Med 2018; 141: 7-13.
Bonecchi R, Bianchi G, Bordignon PP et al. Differential expression of chemokine receptors and chemotactic responsiveness of type 1 T helper cells (Th1s) and Th2s. J Exp Med 1998; 187: 129-34.
Sato S, Kuwana M, Fujita T, Suzuki Y. Anti-CADM-140/MDA5 autoantibody titer correlates with disease activity and predicts disease outcome in patients with dermatomyositis and rapidly progressive interstitial lung disease. Mod Rheumatol 2013; 23: 496-502.
Takeuchi O, Akira S. MDA5/RIG-I and virus recognition. Curr Opin Immunol 2008; 20: 17-22.
Regamey N, Obregon C, Ferrari-Lacraz S et al. Airway epithelial IL-15 transforms monocytes into dendritic cells. Am J Respir Cell Mol Biol 2007; 37: 75-84.
Gono T, Miyake K, Kawaguchi Y, Kaneko H, Shinozaki M, Yamanaka H. Hyperferritinaemia and macrophage activation in a patient with interstitial lung disease with clinically amyopathic DM. Rheumatology 2012; 51: 1336-8.
Mercer PF, Williams AE, Scotton CJ et al. Proteinase-activated receptor-1, CCL2, and CCL7 regulate acute neutrophilic lung inflammation. Am J Respir Cell Mol Biol 2014; 50: 144-57.