Increased serum soluble interleukin-2 receptor levels in dermatomyositis are associated with Th17/Treg immune imbalance.


Journal

Clinical and experimental medicine
ISSN: 1591-9528
Titre abrégé: Clin Exp Med
Pays: Italy
ID NLM: 100973405

Informations de publication

Date de publication:
Nov 2023
Historique:
received: 25 12 2022
accepted: 24 07 2023
medline: 2 11 2023
pubmed: 2 8 2023
entrez: 1 8 2023
Statut: ppublish

Résumé

Dermatomyositis (DM) represents a multifaceted chronic inflammatory myopathy, primarily manifesting as progressive deterioration of muscular and cutaneous tissues. Despite an incomplete comprehension of DM's etiology and pathogenesis, current evidence implicates the involvement of T lymphocyte infiltration, extensive cytokine release, myositis-specific antibodies, and myositis-associated antibodies in disease development. Serum soluble interleukin-2 receptor (sIL-2R) frequently serves as a marker for T cell activation; however, its role remains elusive. Consequently, this investigation sought to elucidate the association between sIL-2R levels, peripheral blood lymphocyte subset counts, and related cytokines in DM patients, with the aim of uncovering the intricate mechanisms underlying DM and establishing a theoretical foundation for the implementation of precise, targeted, individualized immunomodulatory therapy. In this study, a cohort of 60 dermatomyositis (DM) patients, comprising 32 with inactive DM and 28 with active DM, was enrolled and stratified into inactive and active groups based on the Myositis Disease Activity Visual Analogue Scale (MYOACT). Flow cytometry was employed to quantify the absolute counts of peripheral lymphocyte subsets and CD4+T cell subsets in each group, while a flow cytometry bead array was utilized to measure serum cytokine levels. In a comparative analysis between healthy individuals and patients diagnosed with DM, we observed a marked elevation in serum sIL-2R concentrations (P < 0.001) and T-helper 17 cell/regulatory T cell (Th17/Treg) ratios (P < 0.01) within the latter group. A positive correlation was identified between serum sIL-2R levels and various parameters, including ESR, CRP, VAS, AST, CKMB, LDH, HBDH, PT, APTT, DDi, IL-6, IL-10, and IFN-γlevels (P < 0.05). In contrast, serum sIL-2R levels demonstrated a negative correlation with LY, HGB, ALB, Th17 cell populations, and Th17/Treg cell ratios (P < 0.05). Employing multivariate logistic regression, we identified serum sIL-2R concentrations as an independent risk factor for both disease activity and hepatic involvement in DM patients. Moreover, receiver operating characteristic (ROC) curve analyses revealed that serum sIL-2R levels significantly contributed to the differentiation of disease activity and the detection of liver involvement in DM patients, with areas under the ROC curve (AUC) of 0.757 (95% CI 0.630-0.884, P = 0.001) and 0.826 (95% CI 0.717-0.935, P < 0.001), respectively. This study highlights the potential utility of serum sIL-2R levels as a valuable biomarker for assessing disease activity and liver involvement in dermatomyositis. Elevated serum concentrations of sIL-2R were observed in patients with DM, exhibiting significant associations with Th17 cell populations and Th17/ Treg ratios. These findings indicate that sIL-2R may be implicated in the immunopathogenesis of DM, thereby warranting further investigation to elucidate its role in the disease process.

Identifiants

pubmed: 37528249
doi: 10.1007/s10238-023-01155-5
pii: 10.1007/s10238-023-01155-5
doi:

Substances chimiques

Receptors, Interleukin-2 0
Cytokines 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

3605-3617

Informations de copyright

© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.

Références

Lundberg IE, Fujimoto M, Vencovsky J, et al. Idiopathic inflammatory myopathies. Nat Rev Dis Primers. 2021;7(1):86.
doi: 10.1038/s41572-021-00321-x pubmed: 34857798
Rothwell S, Lamb JA, Chinoy H. New developments in genetics of myositis. Curr Opin Rheumatol. 2016;28(6):651–6.
doi: 10.1097/BOR.0000000000000328 pubmed: 27466937
Miller FW, Lamb JA, Schmidt J, Nagaraju K. Risk factors and disease mechanisms in myositis. Nat Rev Rheumatol. 2018;14(5):255–68.
doi: 10.1038/nrrheum.2018.48 pubmed: 29674613 pmcid: 6745704
Lundberg IE, Tjärnlund 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(12):1955–64.
doi: 10.1136/annrheumdis-2017-211468 pubmed: 29079590
Selva-O’Callaghan A, Pinal-Fernandez I, Trallero-Araguás E, Milisenda JC, Grau-Junyent JM, Mammen AL. Classification and management of adult inflammatory myopathies. Lancet Neurol. 2018;17(9):816–28.
doi: 10.1016/S1474-4422(18)30254-0 pubmed: 30129477
Satoh M, Tanaka S, Ceribelli A, Calise SJ, Chan EK. A comprehensive overview on myositis-specific antibodies: new and old biomarkers in idiopathic inflammatory myopathy. Clin Rev Allergy Immunol. 2017;52(1):1–19.
doi: 10.1007/s12016-015-8510-y pubmed: 26424665 pmcid: 5828023
Smith KA. Interleukin-2: inception, impact, and implications. Science. 1988;240(4856):1169–76.
doi: 10.1126/science.3131876 pubmed: 3131876
Spolski R, Li P, Leonard WJ. Biology and regulation of IL-2: from molecular mechanisms to human therapy. Nat Rev Immunol. 2018;18(10):648–59.
doi: 10.1038/s41577-018-0046-y pubmed: 30089912
He J, Chen J, Miao M, et al. Efficacy and safety of low-dose interleukin 2 for primary sjögren syndrome: a randomized clinical trial. JAMA Netw Open. 2022;5(11): e2241451.
doi: 10.1001/jamanetworkopen.2022.41451 pubmed: 36355371 pmcid: 9650609
Humrich JY, von Spee-Mayer C, Siegert E, et al. Rapid induction of clinical remission by low-dose interleukin-2 in a patient with refractory SLE. Ann Rheum Dis. 2015;74(4):791–2.
doi: 10.1136/annrheumdis-2014-206506 pubmed: 25609413
Rosenzwajg M, Churlaud G, Mallone R, et al. Low-dose interleukin-2 fosters a dose-dependent regulatory T cell tuned milieu in T1D patients. J Autoimmun. 2015;58:48–58.
doi: 10.1016/j.jaut.2015.01.001 pubmed: 25634360 pmcid: 8153751
Rubin LA, Nelson DL. The soluble interleukin-2 receptor: biology, function, and clinical application. Ann Intern Med. 1990;113(8):619–27.
doi: 10.7326/0003-4819-113-8-619 pubmed: 2205142
Liao W, Lin JX, Leonard WJ. IL-2 family cytokines: new insights into the complex roles of IL-2 as a broad regulator of T helper cell differentiation. Curr Opin Immunol. 2011;23(5):598–604.
doi: 10.1016/j.coi.2011.08.003 pubmed: 21889323 pmcid: 3405730
Chen J, Jin Y, Li C, et al. Evaluation of soluble CD25 as a clinical and autoimmune biomarker in primary Sjögren’s syndrome. Clin Exp Rheumatol. 2020;126(4):142–9.
Zhang RJ, Zhang X, Chen J, et al. Serum soluble CD25 as a risk factor of renal impairment in systemic lupus erythematosus: a prospective cohort study. Lupus. 2018;27(7):1100–6.
doi: 10.1177/0961203318760993 pubmed: 29482443
Eurelings LEM, Miedema JR, Dalm V, et al. Sensitivity and specificity of serum soluble interleukin-2 receptor for diagnosing sarcoidosis in a population of patients suspected of sarcoidosis. PLoS ONE. 2019;14(10): e0223897.
doi: 10.1371/journal.pone.0223897 pubmed: 31622413 pmcid: 6797090
Handa T, Matsui S, Yoshifuji H, et al. Serum soluble interleukin-2 receptor as a biomarker in immunoglobulin G4-related disease. Mod Rheumatol. 2018;28(5):838–44.
doi: 10.1080/14397595.2017.1416739 pubmed: 29251035
He L, Shu X, Liu X, et al. Soluble IL-2 Receptor in Dermatomyositis: Its Associations with Skin Ulcers and Disease Activity. Mediators Inflamm. 2020;2020:6243019.
doi: 10.1155/2020/6243019 pubmed: 32774147 pmcid: 7407014
Bohan A, Peter JB. Polymyositis and dermatomyositis (first of two parts). N Engl J Med. 1975;292(7):344–7.
doi: 10.1056/NEJM197502132920706 pubmed: 1090839
Bohan A, Peter JB. Polymyositis and dermatomyositis (second of two parts). N Engl J Med. 1975;292(8):403–7.
doi: 10.1056/NEJM197502202920807 pubmed: 1089199
Tournadre A, Dubost JJ, Soubrier M, et al. Soluble IL-2 receptor: a biomarker for assessing myositis activity. Dis Markers. 2014;2014: 472624.
doi: 10.1155/2014/472624 pubmed: 24648607 pmcid: 3932274
Mielnik P, Chwalinska-Sadowska H, Wiesik-Szewczyk E, Maslinski W, Olesinska M. Serum concentration of interleukin 15, interleukin 2 receptor and TNF receptor in patients with polymyositis and dermatomyositis: correlation to disease activity. Rheumatol Int. 2012;32(3):639–43.
doi: 10.1007/s00296-010-1692-y pubmed: 21132303
Levi M, van der Poll T. Inflammation and coagulation. Crit Care Med. 2010;38(2 Suppl):S26-34.
doi: 10.1097/CCM.0b013e3181c98d21 pubmed: 20083910
Zheng CS, Qin XJ, Ni H, Chen RY, Liu JL, Wang WH. Evaluation of disease activity of systemic lupus erythematosus by D-dimer combined with red blood cell distribution width. Clin Lab. 2021;67 (9)
Xue L, Tao L, Li X, et al. Plasma fibrinogen, D-dimer, and fibrin degradation product as biomarkers of rheumatoid arthritis. Sci Rep. 2021;11(1):16903.
doi: 10.1038/s41598-021-96349-w pubmed: 34413382 pmcid: 8377052
Zhang SX, Wang J, Sun HH, et al. Circulating regulatory T cells were absolutely decreased in dermatomyositis/polymyositis patients and restored by low-dose IL-2. Ann Rheum Dis. 2021;80(8): e130.
doi: 10.1136/annrheumdis-2019-216246 pubmed: 31611221
Wu R, Li N, Zhao X, et al. Low-dose Interleukin-2: Biology and therapeutic prospects in rheumatoid arthritis. Autoimmun Rev. 2020;19(10): 102645.
doi: 10.1016/j.autrev.2020.102645 pubmed: 32801037
Rubinstein MP, Kovar M, Purton JF, et al. Converting IL-15 to a superagonist by binding to soluble IL-15R{alpha}. Proc Natl Acad Sci U S A. 2006;103(24):9166–71.
doi: 10.1073/pnas.0600240103 pubmed: 16757567 pmcid: 1482584
Boyman O, Sprent J. The role of interleukin-2 during homeostasis and activation of the immune system. Nat Rev Immunol. 2012;12(3):180–90.
doi: 10.1038/nri3156 pubmed: 22343569
Dong C. TH17 cells in development: an updated view of their molecular identity and genetic programming. Nat Rev Immunol. 2008;8(5):337–48.
doi: 10.1038/nri2295 pubmed: 18408735
Sanders JM, Jeyamogan S, Mathew JM, Leventhal JR. Foxp3+ regulatory T cell therapy for tolerance in autoimmunity and solid organ transplantation. Front Immunol. 2022;13:1055466.
doi: 10.3389/fimmu.2022.1055466 pubmed: 36466912 pmcid: 9714335
Sutton CE, Lalor SJ, Sweeney CM, Brereton CF, Lavelle EC, Mills KH. Interleukin-1 and IL-23 induce innate IL-17 production from gammadelta T cells, amplifying Th17 responses and autoimmunity. Immunity. 2009;31(2):331–41.
doi: 10.1016/j.immuni.2009.08.001
Rachitskaya AV, Hansen AM, Horai R, et al. Cutting edge: NKT cells constitutively express IL-23 receptor and RORgammat and rapidly produce IL-17 upon receptor ligation in an IL-6-independent fashion. J Immunol. 2008;180(8):5167–71.
doi: 10.4049/jimmunol.180.8.5167 pubmed: 18390697
Langen RC, Schols AM, Kelders MC, Van Der Velden JL, Wouters EF, Janssen-Heininger YM. Tumor necrosis factor-alpha inhibits myogenesis through redox-dependent and -independent pathways. Am J Physiol Cell Physiol. 2002;283(3):C714–21.
doi: 10.1152/ajpcell.00418.2001 pubmed: 12176728
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(1):240.
doi: 10.1186/s13075-018-1737-2 pubmed: 30367666 pmcid: 6235206
Gono T, Kaneko H, Kawaguchi Y, et al. Cytokine profiles in polymyositis and dermatomyositis complicated by rapidly progressive or chronic interstitial lung disease. Rheumatology (Oxford). 2014;53(12):2196–203.
doi: 10.1093/rheumatology/keu258 pubmed: 24970922
Zhang M, Zhang S. T Cells in fibrosis and fibrotic diseases. Front Immunol. 2020;11:1142.
doi: 10.3389/fimmu.2020.01142 pubmed: 32676074 pmcid: 7333347

Auteurs

Yuhuan Xie (Y)

Department of Rheumatology, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.
Shanxi Key Laboratory of Immunomicroecology, Taiyuan, Shanxi, China.

Tingting Zhang (T)

Department of Rheumatology, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.
Shanxi Key Laboratory of Immunomicroecology, Taiyuan, Shanxi, China.

Rui Su (R)

Department of Rheumatology, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.
Shanxi Key Laboratory of Immunomicroecology, Taiyuan, Shanxi, China.

Lu Liu (L)

Department of Rheumatology, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.
Shanxi Key Laboratory of Immunomicroecology, Taiyuan, Shanxi, China.

Lei Jiang (L)

Department of Rheumatology, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.
Shanxi Key Laboratory of Immunomicroecology, Taiyuan, Shanxi, China.

Hongwei Xue (H)

Department of Rheumatology, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.
Shanxi Key Laboratory of Immunomicroecology, Taiyuan, Shanxi, China.

Chong Gao (C)

Pathology, Joint Program in Transfusion Medicine, Brigham and Women's Hospital/Children's Hospital, Harvard Medical School, Boston, MA, USA.

Xiaofeng Li (X)

Department of Rheumatology, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.
Shanxi Key Laboratory of Immunomicroecology, Taiyuan, Shanxi, China.

Caihong Wang (C)

Department of Rheumatology, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China. snwch@sina.com.
Shanxi Key Laboratory of Immunomicroecology, Taiyuan, Shanxi, China. snwch@sina.com.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female
Humans United States Aged Cross-Sectional Studies Medicare Part C
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH