Milk fat globule E-8 and interleukin 17 in systemic lupus erythematosus: partners in crime?
Data nadesłania: 14-10-2015
Data ostatniej rewizji: 15-12-2015
Data akceptacji: 09-01-2016
Data publikacji online: 11-02-2016
Data publikacji: 15-02-2016
Reumatologia 2015;53(6):309-314
Objectives: Systemic lupus erythematosus (SLE) is a multi-factorial, autoimmune disease with a wide array of manifestations. The pro-inflammatory cytokine interleukin (IL)-17 has been implicated in the inflammatory response and tissue damage in SLE; however, its correlation with disease activity is still questionable. Meanwhile, efficient clearance of apoptotic cells is required for immune tolerance. An abnormally low or high level of milk fat globule (MFG-E8) can result in impaired apoptotic cell clearance and the subsequent autoimmune response. In this study, we endeavoured to compare the levels of MFG-E8 and IL-17 in SLE patients and healthy controls and to reveal the alleged association of these levels with SLE disease activity.
Material and methods: Serum samples from 57 SLE patients and 30 healthy control subjects were examined for quantitation of MFG-E8 and IL-17 levels using ELISA. Systemic lupus erythematosus disease activity was calculated using the SLE Disease Activity Index (SLEDAI). Clinical manifestations and laboratory findings of the patients were also recorded.
Results: We report that serum MFG-E8 levels were significantly elevated in the sera of SLE patients compared to healthy controls (p-value = 0.019). Likewise, IL-17 levels were higher in SLE patients (p-value < 0.001). A positive correlation was revealed between MFG-E8 level and proteinuria. Surprisingly, there was a poor correlation between disease activity and the levels of either IL-17 or MFG-E8.
Conclusions: Although serum MFG-E8 and IL-17 levels were higher in SLE patients than in normal controls, our results indicate that they cannot accurately reflect the disease activity. Meanwhile, further studies are needed to assess MFG-E8 and IL-17 as potential therapeutic targets in SLE patients.
Borchers AT, Naguwa SM, Shoenfeld Y, Gershwin ME. The geoepidemiology of systemic lupus erythematosus. Autoimmun Rev 2010; 9: A277-A287.
Truchetet ME, Mossalayi MD, Boniface K. IL-17 in the rheumatologist’s line of sight. BioMed Res Int 2013; Article ID 295132.
Adalid-Peralta L, Mathian A, Tran T, et al. Leukocytes and the kidney contribute to interstitial inflammation in lupus nephritis. Kidney Int 2008; 73: 172-180.
Hofstetter HH, Ibrahim SM, Koczan D, et al. Therapeutic efficacy of IL-17 neutralization in murine experimental autoimmune encephalomyelitis. Cell Immunol 2005; 237: 123-130.
Crispin JC, Kyttaris VC, Juang YT, Tsokos GC. How signalling and gene transcription aberrations dictate the systemic lupus erythematosus T cell phenotype. Trends Immunol 2008; 29: 110-115.
Ambrosi A, Espinosa A, Wahren-Herlenius M. IL-17: A new actor in IFN-driven systemic autoimmune diseases. Eur J Immunol 2012; 42: 2274-2284.
Bettelli E, Carrier Y, Gao W, et al. Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature 2006; 441: 235-238.
Langrish CL, Chen Y, Blumenschein WM, et al. IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J Exp Med 2005; 201: 233-240.
Korn T, Oukka M, Kuchroo V, Bettelli E. Th17 cells: effector T cells with inflammatory properties. Semin Immunol 2007; 19: 362-371.
Crispin JC, Oukka M, Bayliss G, et al. Expanded double negative T cells in patients with systemic lupus erythematosus produce IL-17 and infiltrate the kidneys. J Immunol 2008; 181: 8761-8766.
Jovanovic DV, Di Battista JA, Martel-Pelletier J, et al. IL-17 stimulates the production and expression of proinflammatory cytokines, IL- and TNF-, by human macrophages. J Immunol 1998; 160: 3513-3521.
Doreau A, Belot A, Bastid J, et al. Interleukin 17 acts in synergy with B cell-activating factor to influence B cell biology and the pathophysiology of systemic lupus erythematosus. Nat Immunol 2009; 10: 778-785.
Agarwal S, Misra R, Aggarwal A. Interleukin 17 levels are increased in juvenile idiopathic arthritis synovial fluid and induce synovial fibroblasts to produce proinflammatory cytokines and matrix metalloproteinases. J Rheumatol 2008; 35: 515-519.
Albanesi C, Cavani A, Girolomoni G. IL-17 is produced by nickelspecific T lymphocytes and regulates ICAM-1 expression and chemokine production in human keratinocytes: synergistic or antagonist effects with IFN-gamma and TNF-alpha. J Immunol 1999; 162: 494-502.
Schwarzenberger P, Huang W, Ye P, et al. Requirement of endogenous stem cell factor and granulocyte-colony-stimulating factor for IL-17-mediated granulopoiesis. J Immunol 2000; 164: 4783-4789.
Shah K, Lee WW, Lee SH, et al. Dysregulated balance of Th17 and Th1 cells in systemic lupus erythematosus. Arthritis Res Ther 2010; 12: R53.
Perricone C, Ciccacci C, Ceccarelli F, et al. TRAF3IP2 gene and systemic lupus erythematosus: association with disease susceptibility and pericarditis development. Immunogenetics 2013; 65: 703-709.
Ciccacci C, Perricone C, Ceccarelli F, et al. A multilocus genetic study in a cohort of Italian SLE patients confirms the association with STAT4 gene and describes a new association with HCP5 gene. PLoS One 2014; 9: e111991.
Munoz LE, Lauber K, Schiller M, et al. The role of defective clearance of apoptotic cells in systemic autoimmunity. Nat Rev Rheumatol 2010; 6: 280-289.
Shao WH, Cohen PL. Disturbances of apoptotic cell clearance in systemic lupus erythematosus. Arthritis Res Ther 2011; 13: 202.
Fadeel B, Xue D, Kagan V. Programmed cell clearance: molecular regulation of the elimination of apoptotic cell corpses and its role in the resolution of inflammation. Biochem Biophys Res Commun 2010; 396: 7-10.
Hanayama R, Tanaka M, Miwa K, et al. Identification of a factor that links apoptotic cells to phagocytes. Nature 2002; 417: 182-187.
Yamaguchi H, Takagi J, Miyamae T, et al. Milk fat globule EGF factor 8 in the serum of human patients of systemic lupus erythematosus. J Leukoc Biol 2008; 83: 1300-1307.
Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1997; 40: 1725-1725.
Wang Y, Ito S, Chino Y, et al. Laser microdissection – based analysis of cytokine balance in the kidneys of patients with lupus nephritis. Clin Exp Immunol 2010; 159: 1-10.
Zhao XF, Pan HF, Yuan H, et al. Increased serum interleukin 17 in patients with systemic lupus erythematosus. Mol Biol Rep 2010; 37: 81-85.
Vincent FB, Northcott M, Hoi A, et al. Clinical associations of serum interleukin-17 in systemic lupus erythematosus. Arthritis Res Ther 2013; 15: R97.
Zhu S, Qian Y. IL-17/IL-17 receptor system in autoimmune disease: mechanisms and therapeutic potential. Clin Sci 2012; 122: 487-511.
Yamamoto NH, Yamaguchi K, Ohmura T, et al. Serum milk fat globule epidermal growth factor 8 elevation may subdivide systemic lupus erythematosus into two pathophysiologically distinct subsets. Lupus 2014; 23: 386-394.
Aziz MM, Ishihara S, Rumi MA, et al. Prolactin induces MFG-E8 production in macrophages via transcription factor C/EBP beta-dependent pathway. Apoptosis 2008; 13: 609-620.
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