Skip to main content
Erschienen in: Clinical Rheumatology 11/2016

08.08.2016 | Original Article

The clinical utility of serum IL-35 in patients with polymyositis and dermatomyositis

verfasst von: Liguo Yin, Yongpeng Ge, Hanbo Yang, Qinglin Peng, Xin Lu, Yamei Zhang, Guochun Wang

Erschienen in: Clinical Rheumatology | Ausgabe 11/2016

Einloggen, um Zugang zu erhalten

Abstract

The objectives of this study are to assess the levels of serum Interleukin-35 (IL-35) in patients with idiopathic inflammatory myopathies (IIMs) and to evaluate the association between IL-35 levels and IIM-related features. Serum IL-35 was detected in 76 patients with dermatomyositis (DM), 28 patients with polymyositis (PM), 98 disease controls (40 rheumatoid arthritis (RA), 34 systemic lupus erythematosus (SLE), 12 systemic sclerosis (SSc), and 12 sjogren syndrome (SS)), and 43 healthy controls by ELISA. Follow-up was conducted on 34 patients. Serum IL-35 was higher in myositis (PM/DM) patients than in healthy controls (median 76.6 pg/ml [interquartile range (IQR) 57.9–136.2] vs. 29.9 pg/ml (IQR 21.9–65.5), P < 0.001) and disease controls. Serum IL-35 in IIM patients negatively correlated with disease duration moderately (r = −0.35, P < 0.01). Patients with dysphagia had higher IL-35 than those without (median149.35 pg/ml (IQR 87.97–267.32) vs. 70.72 pg/ml (IQR 54.49–123.42), P = 0.001). Cross-sectional correlation analysis showed a weak positive correlation between serum IL-35 and CK (r = 0.293, P = 0.003), moderate positive correlation with erythrocyte sedimentation rate (ESR) (r = 0.304, P = 0.002), serum ferritin (SF) (r = 0.467, P = 0.001) and LDH levels (r = 0.401, P < 0.001). Additionally, serum IL-35 was higher in patients who were positive for anti-HMGCR (median 292.04 pg/ml (IQR 67.9–442.86) vs. 74.66 pg/ml (IQR 57.24–131.32), P = 0.038) and anti-SRP antibody (median 130.33 pg/ml (IQR 88.04–481.28) vs. 73.06 pg/ml (IQR 56.78–134.28), P = 0.009) than in negative patients, respectively. Follow-up study showed that changes in IL-35 levels after treatment correlated with changes in MYOACT scores moderately (r = 0.375, P = 0.029). These data indicate that increased serum IL-35 could act as a disease activity marker and as a risk factor for esophageal involvement in IIM. IL-35 may participate in the pathophysiological processes of IIM, but it still needs further study to confirm.
Literatur
2.
3.
Zurück zum Zitat Dalakas MC (1991) Polymyositis, dermatomyositis and inclusion-body myositis. N Engl J Med 325:1487–1498CrossRefPubMed Dalakas MC (1991) Polymyositis, dermatomyositis and inclusion-body myositis. N Engl J Med 325:1487–1498CrossRefPubMed
4.
Zurück zum Zitat Mei Z, Lundberg IE (2011) Pathogenesis, classification and treatment of inflammatory myopathies. Nat Rev Rheumatol 7:297–306CrossRef Mei Z, Lundberg IE (2011) Pathogenesis, classification and treatment of inflammatory myopathies. Nat Rev Rheumatol 7:297–306CrossRef
5.
Zurück zum Zitat Lundberg IE (2000) The role of cytokines, chemokines, and adhesion molecules in the pathogenesis of idiopathic inflammatory myopathies. Curr Rheumatol Rep 2:216–224CrossRefPubMed Lundberg IE (2000) The role of cytokines, chemokines, and adhesion molecules in the pathogenesis of idiopathic inflammatory myopathies. Curr Rheumatol Rep 2:216–224CrossRefPubMed
6.
Zurück zum Zitat Collison LW, Workman CJ, Kuo TT, et al. (2007) The inhibitory cytokine IL-35 contributes to regulatory T-cell function. Nature 450:566–569CrossRefPubMed Collison LW, Workman CJ, Kuo TT, et al. (2007) The inhibitory cytokine IL-35 contributes to regulatory T-cell function. Nature 450:566–569CrossRefPubMed
7.
Zurück zum Zitat Bardel E, Larousserie F, Charlot-Rabiega P, et al. (2008) Human CD4+CD25+Foxp3+ regulatory T cells do not constitutively express IL-35. J Immunol 181:6898–6905CrossRefPubMed Bardel E, Larousserie F, Charlot-Rabiega P, et al. (2008) Human CD4+CD25+Foxp3+ regulatory T cells do not constitutively express IL-35. J Immunol 181:6898–6905CrossRefPubMed
8.
Zurück zum Zitat Allan SE, Song-Zhao GX, Abraham T, et al. (2008) Inducible reprogramming of human T cells into Treg cells by a conditionally active form of FOXP3. Eur J Immunol 38:3282–3289CrossRefPubMed Allan SE, Song-Zhao GX, Abraham T, et al. (2008) Inducible reprogramming of human T cells into Treg cells by a conditionally active form of FOXP3. Eur J Immunol 38:3282–3289CrossRefPubMed
9.
Zurück zum Zitat Collison LW, Chaturvedi V, Henderson AL, et al. (2010) IL-35-mediated induction of a potent regulatory T cell population. Nat Immunol 11:1093–1101CrossRefPubMedPubMedCentral Collison LW, Chaturvedi V, Henderson AL, et al. (2010) IL-35-mediated induction of a potent regulatory T cell population. Nat Immunol 11:1093–1101CrossRefPubMedPubMedCentral
10.
Zurück zum Zitat Filkova M, Vernerova Z, Hulejova H, et al. (2015) Pro-inflammatory effects of interleukin-35 in rheumatoid arthritis. Cytokine 73:36–43CrossRefPubMed Filkova M, Vernerova Z, Hulejova H, et al. (2015) Pro-inflammatory effects of interleukin-35 in rheumatoid arthritis. Cytokine 73:36–43CrossRefPubMed
11.
Zurück zum Zitat Kuo J, Nardelli DT, Warner TF, et al. (2011) Interleukin-35 enhances Lyme arthritis in Borrelia-vaccinated and -infected mice. Clin Vaccine Immunol: CVI 18:1125–1132CrossRefPubMedPubMedCentral Kuo J, Nardelli DT, Warner TF, et al. (2011) Interleukin-35 enhances Lyme arthritis in Borrelia-vaccinated and -infected mice. Clin Vaccine Immunol: CVI 18:1125–1132CrossRefPubMedPubMedCentral
12.
Zurück zum Zitat Thiolat A, Denys A, Petit M, et al. (2014) Interleukin-35 gene therapy exacerbates experimental rheumatoid arthritis in mice. Cytokine 69:87–93CrossRefPubMed Thiolat A, Denys A, Petit M, et al. (2014) Interleukin-35 gene therapy exacerbates experimental rheumatoid arthritis in mice. Cytokine 69:87–93CrossRefPubMed
13.
Zurück zum Zitat Niedbala W, Wei XQ, Cai B, et al. (2007) IL-35 is a novel cytokine with therapeutic effects against collagen-induced arthritis through the expansion of regulatory T cells and suppression of Th17 cells. Eur J Immunol 37:3021–3029CrossRefPubMed Niedbala W, Wei XQ, Cai B, et al. (2007) IL-35 is a novel cytokine with therapeutic effects against collagen-induced arthritis through the expansion of regulatory T cells and suppression of Th17 cells. Eur J Immunol 37:3021–3029CrossRefPubMed
14.
15.
Zurück zum Zitat Bohan APJ (1975) Polymyositis and dermatomyositis (second of two parts). N Engl J Med 292:403–407CrossRefPubMed Bohan APJ (1975) Polymyositis and dermatomyositis (second of two parts). N Engl J Med 292:403–407CrossRefPubMed
16.
Zurück zum Zitat Bohan APJ (1975) Polymyositis and dermatomyositis (first of two parts). N Engl J Med 292:344–347CrossRefPubMed Bohan APJ (1975) Polymyositis and dermatomyositis (first of two parts). N Engl J Med 292:344–347CrossRefPubMed
17.
Zurück zum Zitat Isenberg DA, Allen E, Farewell V, et al. (2004) International consensus outcome measures for patients with idiopathic inflammatory myopathies development and initial validation of myositis activity and damage indices in patients with adult onset disease. Rheumatology (Oxford) 43:49–54CrossRef Isenberg DA, Allen E, Farewell V, et al. (2004) International consensus outcome measures for patients with idiopathic inflammatory myopathies development and initial validation of myositis activity and damage indices in patients with adult onset disease. Rheumatology (Oxford) 43:49–54CrossRef
18.
Zurück zum Zitat Bettelli E, Korn T, Oukka M, et al. (2008) Induction and effector functions of T(H)17 cells. Nature 453:1051–1057CrossRefPubMed Bettelli E, Korn T, Oukka M, et al. (2008) Induction and effector functions of T(H)17 cells. Nature 453:1051–1057CrossRefPubMed
19.
Zurück zum Zitat Llorente L, Zou W, Levy Y, et al. (1995) Role of interleukin 10 in the B lymphocyte hyperactivity and autoantibody production of human systemic lupus erythematosus. J Exp Med 181:839–844CrossRefPubMed Llorente L, Zou W, Levy Y, et al. (1995) Role of interleukin 10 in the B lymphocyte hyperactivity and autoantibody production of human systemic lupus erythematosus. J Exp Med 181:839–844CrossRefPubMed
20.
Zurück zum Zitat Macneil IA, Suda T, Moore KW, et al. (1990) IL-10, a novel growth cofactor for mature and immature T cells. J Immunol 145:4167–4173PubMed Macneil IA, Suda T, Moore KW, et al. (1990) IL-10, a novel growth cofactor for mature and immature T cells. J Immunol 145:4167–4173PubMed
21.
Zurück zum Zitat Shachar I, Karin N (2013) The dual roles of inflammatory cytokines and chemokines in the regulation of autoimmune diseases and their clinical implications. J Leukoc Biol 93:51–61CrossRefPubMed Shachar I, Karin N (2013) The dual roles of inflammatory cytokines and chemokines in the regulation of autoimmune diseases and their clinical implications. J Leukoc Biol 93:51–61CrossRefPubMed
22.
Zurück zum Zitat Cai Z, Wong CK, Kam NW, et al. (2015) Aberrant expression of regulatory cytokine IL-35 in patients with systemic lupus erythematosus. Lupus 24 Cai Z, Wong CK, Kam NW, et al. (2015) Aberrant expression of regulatory cytokine IL-35 in patients with systemic lupus erythematosus. Lupus 24
23.
Zurück zum Zitat Qiu F, Song L, Yang N, et al. (2013) Glucocorticoid downregulates expression of IL-12 family cytokines in systemic lupus erythematosus patients. Lupus 22:1011–1016CrossRefPubMed Qiu F, Song L, Yang N, et al. (2013) Glucocorticoid downregulates expression of IL-12 family cytokines in systemic lupus erythematosus patients. Lupus 22:1011–1016CrossRefPubMed
24.
Zurück zum Zitat Banica L, Besliu A, Pistol G, et al. (2009) Quantification and molecular characterization of regulatory T cells in connective tissue diseases. Autoimmunity 42:41–49CrossRefPubMed Banica L, Besliu A, Pistol G, et al. (2009) Quantification and molecular characterization of regulatory T cells in connective tissue diseases. Autoimmunity 42:41–49CrossRefPubMed
25.
Zurück zum Zitat Antiga E, Kretz CC, Klembt R, et al. (2010) Characterization of regulatory T cells in patients with dermatomyositis. J Autoimmun 35:342–350CrossRefPubMed Antiga E, Kretz CC, Klembt R, et al. (2010) Characterization of regulatory T cells in patients with dermatomyositis. J Autoimmun 35:342–350CrossRefPubMed
26.
Zurück zum Zitat Wang DX, Lu X, Zu N, et al. (2012) Clinical significance of peripheral blood lymphocyte subsets in patients with polymyositis and dermatomyositis. Clin Rheumatol 31:1691–1697CrossRefPubMed Wang DX, Lu X, Zu N, et al. (2012) Clinical significance of peripheral blood lymphocyte subsets in patients with polymyositis and dermatomyositis. Clin Rheumatol 31:1691–1697CrossRefPubMed
27.
Zurück zum Zitat Nagaraju, Raben, Merritt, et al. (1998) A variety of cytokines and immunologically relevant surface molecules are expresssed by normal skeletal muscle cells under proinflammatory stimuli. Clin Exp Immunol 113:407–414CrossRefPubMedPubMedCentral Nagaraju, Raben, Merritt, et al. (1998) A variety of cytokines and immunologically relevant surface molecules are expresssed by normal skeletal muscle cells under proinflammatory stimuli. Clin Exp Immunol 113:407–414CrossRefPubMedPubMedCentral
28.
29.
Zurück zum Zitat Seventer JMV, Nagai T, Seventer GAV (2002) Interferon-beta differentially regulates expression of the IL-12 family members p35, p40, p19 and EBI3 in activated human dendritic cells. J Neuroimmunol 133:60–71CrossRefPubMed Seventer JMV, Nagai T, Seventer GAV (2002) Interferon-beta differentially regulates expression of the IL-12 family members p35, p40, p19 and EBI3 in activated human dendritic cells. J Neuroimmunol 133:60–71CrossRefPubMed
30.
Zurück zum Zitat Heidemann J, Rüther C, Kebschull M, et al. (2008) Expression of IL-12-related molecules in human intestinal microvascular endothelial cells is regulated by TLR3. Am J Physiol Gastrointest Liver Physiol 293:G1315–G1324CrossRef Heidemann J, Rüther C, Kebschull M, et al. (2008) Expression of IL-12-related molecules in human intestinal microvascular endothelial cells is regulated by TLR3. Am J Physiol Gastrointest Liver Physiol 293:G1315–G1324CrossRef
31.
Zurück zum Zitat Maaser C, Egan LJ, Birkenbach MP, et al. (2004) Expression of Epstein-Barr virus-induced gene 3 and other interleukin-12-related molecules by human intestinal epithelium. Immunology 112:437–445CrossRefPubMedPubMedCentral Maaser C, Egan LJ, Birkenbach MP, et al. (2004) Expression of Epstein-Barr virus-induced gene 3 and other interleukin-12-related molecules by human intestinal epithelium. Immunology 112:437–445CrossRefPubMedPubMedCentral
32.
Zurück zum Zitat Xinyuan L, Jietang M, Anthony V, et al. (2012) IL-35 is a novel responsive anti-inflammatory cytokine—a new system of categorizing anti-inflammatory cytokines. PLoS One 7:65–65 Xinyuan L, Jietang M, Anthony V, et al. (2012) IL-35 is a novel responsive anti-inflammatory cytokine—a new system of categorizing anti-inflammatory cytokines. PLoS One 7:65–65
33.
Zurück zum Zitat Targoff IN, Johnson AE, Miller FW (1990) Antibody to signal recognition particle in polymyositis. Arthritis Rheum 33:1361–1370CrossRefPubMed Targoff IN, Johnson AE, Miller FW (1990) Antibody to signal recognition particle in polymyositis. Arthritis Rheum 33:1361–1370CrossRefPubMed
34.
Zurück zum Zitat Kao AH, David L, Mary L, et al. (2004) Anti-signal recognition particle autoantibody in patients with and patients without idiopathic inflammatory myopathy. Arthritis Rheum 50:209–215CrossRefPubMed Kao AH, David L, Mary L, et al. (2004) Anti-signal recognition particle autoantibody in patients with and patients without idiopathic inflammatory myopathy. Arthritis Rheum 50:209–215CrossRefPubMed
35.
Zurück zum Zitat Skowron W, Zemanek K, Wojdan K, et al. (2015) The effect of interleukin-35 on the integrity, ICAM-1 expression and apoptosis of human aortic smooth muscle cells. Pharmacol Rep: PR 67:376–381CrossRefPubMed Skowron W, Zemanek K, Wojdan K, et al. (2015) The effect of interleukin-35 on the integrity, ICAM-1 expression and apoptosis of human aortic smooth muscle cells. Pharmacol Rep: PR 67:376–381CrossRefPubMed
Metadaten
Titel
The clinical utility of serum IL-35 in patients with polymyositis and dermatomyositis
verfasst von
Liguo Yin
Yongpeng Ge
Hanbo Yang
Qinglin Peng
Xin Lu
Yamei Zhang
Guochun Wang
Publikationsdatum
08.08.2016
Verlag
Springer London
Erschienen in
Clinical Rheumatology / Ausgabe 11/2016
Print ISSN: 0770-3198
Elektronische ISSN: 1434-9949
DOI
https://doi.org/10.1007/s10067-016-3347-1

Weitere Artikel der Ausgabe 11/2016

Clinical Rheumatology 11/2016 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Echinokokkose medikamentös behandeln oder operieren?

06.05.2024 DCK 2024 Kongressbericht

Die Therapie von Echinokokkosen sollte immer in spezialisierten Zentren erfolgen. Eine symptomlose Echinokokkose kann – egal ob von Hunde- oder Fuchsbandwurm ausgelöst – konservativ erfolgen. Wenn eine Op. nötig ist, kann es sinnvoll sein, vorher Zysten zu leeren und zu desinfizieren. 

Umsetzung der POMGAT-Leitlinie läuft

03.05.2024 DCK 2024 Kongressbericht

Seit November 2023 gibt es evidenzbasierte Empfehlungen zum perioperativen Management bei gastrointestinalen Tumoren (POMGAT) auf S3-Niveau. Vieles wird schon entsprechend der Empfehlungen durchgeführt. Wo es im Alltag noch hapert, zeigt eine Umfrage in einem Klinikverbund.

Proximale Humerusfraktur: Auch 100-Jährige operieren?

01.05.2024 DCK 2024 Kongressbericht

Mit dem demographischen Wandel versorgt auch die Chirurgie immer mehr betagte Menschen. Von Entwicklungen wie Fast-Track können auch ältere Menschen profitieren und bei proximaler Humerusfraktur können selbst manche 100-Jährige noch sicher operiert werden.

Die „Zehn Gebote“ des Endokarditis-Managements

30.04.2024 Endokarditis Leitlinie kompakt

Worauf kommt es beim Management von Personen mit infektiöser Endokarditis an? Eine Kardiologin und ein Kardiologe fassen die zehn wichtigsten Punkte der neuen ESC-Leitlinie zusammen.

Update Innere Medizin

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