Serum Midkine Levels in Systemic Lupus Erythematosus
DOI:
https://doi.org/10.3889/oamjms.2018.315Keywords:
Midkine, Systemic Lupus ErythematosusAbstract
BACKGROUND: Midkine (MK) induces inflammation and could inhibit inducible regulatory T cell differentiation. These reports suggest that MK may play a role in the pathogenesis of autoimmune disease including SLE, but data about MK in SLE patients was still limited, and the role of Midkine in SLE is largely unknown.
AIM: The purpose of this study was to compare serum level MK in SLE patients and control, also analysed the relationship between the serum MK level and disease activity in SLE.
METHODS: This cross-sectional study was conducted in Adam Malik Hospital from January-June 2017. Diagnosis of SLE was established according to the Systemic Lupus International Collaborating Clinics (SLICC) classification criteria, and disease activity was assessed using the Mexican Systemic lupus erythematosus disease activity index (MEX-SLEDAI). Subjects with evidence of malignancy and systemic disease (pulmonary, kidney, liver, metabolic disorder, etc.) were excluded. Data analysis was performed using SPSS 22nd version. P < 0.05 was considered statistically significant.
RESULTS: There were 90 subjects and divided into 2 groups: SLE patients group (n=40) and healthy control groups (n = 50). Midkine levels were increased in the serum of SLE patients compared by health control. There was a significant difference in the median serum Midkine levels between SLE patients and healthy control (P < 0.001). Elevated Midkine serum levels were a significant difference between active disease and remission (P = 0.018).
CONCLUSION: Elevated Midkine serum level could be a marker of SLE disease activity and have a role in the pathogenesis of SLE.Downloads
Metrics
Plum Analytics Artifact Widget Block
References
Buyon JP. Systemic Lupus Erythematosus. In: Klippel JH, Stone JH, Crofford LeJ, White PH, eds. Primer on the Rheumatic Diseases. Springer, 2008:303-338. https://doi.org/10.1007/978-0-387-68566-3_15
Tahernia L, Namazi S, Rezaei N and Ziaee V. Cytokines in systemic lupus eryhtematosus: their role in pathogenesis of disease and possible therapeutic opportunities. Rheum Res. 2017; 2(1):1-9. https://doi.org/10.22631/rr.2017.69997.1010
Jacob N, Stohl W. Cytokine disturbances in systemic lupus erythematosus. Arthritis Res Ther. 2011; 13:228. https://doi.org/10.1186/ar3349 PMid:21745419 PMCid:PMC3239336
Ibusuki M, Fujimori H, Yamamoto Y, Ota K, Ueda M, Shinriki S, et al. Midkine in plasma as a novel breast cancer marker. Cancer Sci. 2009; 100(9):1735–1739. https://doi.org/10.1111/j.1349-7006.2009.01233.x PMid:19538527
Muramatsu T. Midkine and pleiotrophin: two related proteins involved in development, survival, inflammation and tumorigenesis. J Biochem. 2002; 132: 359-371. https://doi.org/10.1093/oxfordjournals.jbchem.a003231 PMid:12204104
Hung YJ, Lin ZH, Cheng TI, Liang CT, Kuo TM and Kao KJ. Serum Midkine as a Prognostic Biomarker for Patients With Hepatocellular Carcinoma. Am J Clin Pathol. 2011; 136:594-603. https://doi.org/10.1309/AJCPWT70XOVXSVGE PMid:21917682
Weckbach LT, Muramatsu T, Walzog B. Midkine in inflammation. Sci World J. 2011; 11:2491–2505. https://doi.org/10.1100/2011/517152 PMid:22235180 PMCid:PMC3253530
Wang J, Takeuchi H, Sonobe Y, Jin S, Mizuno T, Miyakawa S, et al. Inhibition of midkine alleviates experimental autoimmune encephalomyelitis through the expansion of regulatory T cell population. Proc Natl Acad Sci U S A. 2008; 105: 3915-3920. https://doi.org/10.1073/pnas.0709592105 PMid:18319343 PMCid:PMC2268842
Sonobe Y, Li H, Jin S, Kishida S, Kadomatsu K, Takeuchi H, et al. Midkine inhibits inducible regulatory T cell differentiation by suppressing the development of tolerogenic dendritic cells. J Immunol. 2012; 188:2602–2611. https://doi.org/10.4049/jimmunol.1102346 PMid:22323540
Shindo E, Nanki T, Kusunoki N, Shikano K, Kawazoe M, Sato H, et al. The growth factor midkine may play a pathophysiological role in rheumatoid arthritis. Mod Rheumatol. 2016; 1:1–6
Petri M, Orbai AM, Alarcon GS, et al. Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum. 2012;64:2677. https://doi.org/10.1002/art.34473 PMid:22553077 PMCid:PMC3409311
Khanna S, Pal H, Pandey RM, Handa R. The relationship between disease activity and quality of life in systemic lupus erythematosus. Rheumatology. 2004; 43(12):1536-40. https://doi.org/10.1093/rheumatology/keh376 PMid:15342925
Scheinecker C, Bonelli M and Smolen JS. Pathogenetic aspects of systemic lupus erythematosus with an emphasis on regulatory T cells. J Autoimmun. 2010; 35: 269-275. https://doi.org/10.1016/j.jaut.2010.06.018 PMid:20638240
Ohi K and Tenbrock K. Regulatory T cells in systemic lupus erythematosus. Eur J Immunol. 2015; 45(2):344-355. https://doi.org/10.1002/eji.201344280 PMid:25378177
Liu Z, Davidson A. Taming lupus-a new understanding of pathogenesis is leading to clinical advances. Nat Med. 2012; 18: 871-882. https://doi.org/10.1038/nm.2752 PMid:22674006 PMCid:PMC3607103
Masuda T, Maeda K, Sato W, et al. Growth factor midkine promotes nuclear factor of activated T cells-regulated T-cell- activation and Th1 cell differentiation in lupus nephritis. Am J Pathol. 2017; 184(4):740-751. https://doi.org/10.1016/j.ajpath.2016.12.006 PMid:28183532
Wu GC, Yuan H, Pan HF, Ye DQ. Elevated plasma midkine and pleiotrophin levels in patients with systemic lupus erythematosus. Oncotarget. 2017; 8(25): 40181-40189. https://doi.org/10.18632/oncotarget.13658 PMid:27903979 PMCid:PMC5522313
Shaygannejad V, Montazeri S, Jamshidian A, et al. Correlation of midkine serum level with pro-and anti-inflamatory cytokines in multiple sclerosis. Iran J Immunol. 2014; 11:134–138. PMid:24975970
Krzystek-Korpacka M, Neubauer K, Matusiewicz M. Clinical relevance of circulating midkine in ulcerative colitis. Clin Chem Lab Med. 2009; 47:1085–1090. https://doi.org/10.1515/CCLM.2009.248 PMid:19728850
Krzystek-Korpacka M, Neubauer K, Matusiewicz M. Circulating midkine in Crohn's disease: clinical implications. Inflamm Bowel Dis. 2010; 16:208–215. https://doi.org/10.1002/ibd.21011 PMid:19572374
Downloads
Published
How to Cite
Issue
Section
License
http://creativecommons.org/licenses/by-nc/4.0
