Pathogenese und neue Therapieans盲tze beim systemischen Lupus erythematosus

详细信息    查看全文

• 作者：PD Dr. K. Tenbrock (1)
  
• 关键词：Interferon ; Interleukin ; 2 ; Belimumab ; Antik枚rper ; genomweite Assoziationsstudie ; Interferon ; Interleukin 2 ; Belimumab ; Antibody ; Genome ; wide association study
• 刊名：Zeitschrift f篓鹿r Rheumatologie
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：73
• 期：10
• 页码：890-896
• 全文大小：572 KB
• 参考文献：1. Perl A (2010) Pathogenic mechanisms in systemic lupus erythematosus. Autoimmunity 43:1鈥? CrossRef
  2. Johnson AE, Gordon C, Palmer RG, Bacon PA (1995) The prevalence and incidence of systemic lupus erythematosus in Birmingham, England. Relationship to ethnicity and country of birth. Arthritis Rheum 38:551鈥?58 CrossRef
  3. Tan EM, Cohen AS, Fries JF et al (1982) The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 25:1271鈥?277 CrossRef
  4. Ozbek S, Sert M, Paydas S, Soy M (2003) Delay in the diagnosis of SLE: the importance of arthritis/arthralgia as the initial symptom. Acta Med Okayama 57:187鈥?90
  5. Wandstrat AE, Carr-Johnson F, Branch V et al (2006) Autoantibody profiling to identify individuals at risk for systemic lupus erythematosus. J Autoimmun 27:153鈥?60 CrossRef
  6. Herrmann M, Voll RE, Zoller OM et al (1998) Impaired phagocytosis of apoptotic cell material by monocyte-derived macrophages from patients with systemic lupus erythematosus. Arthritis Rheum 41:1241鈥?250 CrossRef
  7. Nath SK, Han S, Kim-Howard X et al (2008) A nonsynonymous functional variant in integrin-alpha(M) (encoded by ITGAM) is associated with systemic lupus erythematosus. Nat Genet 40:152鈥?54 CrossRef
  8. Adrianto I, Wen F, Templeton A et al (2011) Association of a functional variant downstream of TNFAIP3 with systemic lupus erythematosus. Nat Genet 43:253鈥?58 CrossRef
  9. Remmers EF, Plenge RM, Lee AT et al (2007) STAT4 and the risk of rheumatoid arthritis and systemic lupus erythematosus. N Engl J Med 357:977鈥?86 CrossRef
  10. Lea WW, Lee YH (2011) The association between the PTPN22 C1858T polymorphism and systemic lupus erythematosus: a meta-analysis update. Lupus 20:51鈥?7 CrossRef
  11. Farres MN, Al-Zifzaf DS, Aly AA, Abd Raboh NM (2011) OX40/OX40L in systemic lupus erythematosus: association with disease activity and lupus nephritis. Ann Saudi Med 31:29鈥?4 CrossRef
  12. Sanz I, Lee FE (2010) B cells as therapeutic targets in SLE. Nat Rev Rheumatol 6:326鈥?37 CrossRef
  13. Edberg JC, Zidovetzki R, Criswell LA et al (2011) Genetic analyses of interferon pathway-related genes reveal multiple new loci associated with systemic lupus erythematosus. Arthritis Rheum 63:2049鈥?057 CrossRef
  14. Han JW, Zheng HF, Cui Y et al (2009) Genome-wide association study in a Chinese Han population identifies nine new susceptibility loci for systemic lupus erythematosus. Nat Genet 41:1234鈥?237 CrossRef
  15. Fernando MM, Stevens CR, Sabeti PC et al (2007) Identifi cation of two independent risk factors for lupus within the MHC in United Kingdom families. PLoS Genet 3:e192 CrossRef
  16. Blanco P, Palucka AK, Gill M et al (2001) Induction of dendritic cell differentiation by IFN-alpha in systemic lupus erythematosus. Science 294:1540鈥?543 CrossRef
  17. Feng D, Stone RC, Eloranta ML et al (2010) Genetic variants and disease-associated factors contribute to enhanced interferon regulatory factor 5 expression in blood cells of patients with systemic lupus erythematosus. Arthritis Rheum 62:562鈥?73
  18. Arasappan D, Tong W, Mummaneni P et al (2011) Metaanalysis of microarray data using a pathway-based approach identifies a 37-gene expression signature for systemic lupus erythematosus in human peripheral blood mononuclear cells. BMC Med 9:65 CrossRef
  19. Hedrich CM, Crispin JC, Tsokos GC (2014) Epigenetic regulation of cytokine expression in systemic lupus erythematosus with special focus on T cells. Autoimmunity 47:234鈥?41 CrossRef
  20. Tenbrock K, Juang YT, Leukert N et al (2006) The transcriptional repressor cAMP response element modulator alpha interacts with histone deacetylase 1 to repress promoter activity. J Immunol 177:6159鈥?164 CrossRef
  21. Koga T, Hedrich CM, Mizui M et al (2014) CaMK4-dependent activation of AKT/mTOR and CREM-伪 underlies autoimmunity-associated Th17 imbalance. J Clin Invest 124:2234鈥?245 CrossRef
  22. Miao CG, Yang YY, He X et al (2013) The emerging role of microRNAs in the pathogenesis of systemic lupus erythematosus. Cell Signal 25:1828鈥?836 cellsig.2013.05.006" target="_blank" title="It opens in new window">CrossRef
  23. Golding A, Hasni S, Illei G, Shevach EM (2013) The percentage of FoxP3+Helios+ Treg cells correlates positively with disease activity in systemic lupus erythematosus. Arthritis Rheum 65:2898鈥?906 CrossRef
  24. Navarra SV, Guzman RM, Gallacher AE et al (2011) Efficacy and safety of belimumab in patients with active systemic lupus erythematosus: a randomised, placebo-controlled, phase 3 trial. Lancet 377:721鈥?31 CrossRef
  25. Zonana-Nacach A, Barr SG, Magder LS, Petri M (2000) Damage in systemic lupus erythematosus and its association with corticosteroids. Arthritis Rheum 43:1801鈥?808 CrossRef
  26. Diaz-Lagares C, Croca S, Sangle S et al (2012) Efficacy of rituximab in 164 patients with biopsy-proven lupus nephritis: pooled data from European cohorts. Autoimmun Rev 11:357鈥?64 CrossRef
  27. Merrill JT, Wallace DJ, Petri M et al (2011) Safety profile and clinical activity of sifalimumab, a fully human antiinterferon alpha monoclonal antibody, in systemic lupus erythematosus: a phase I, multicentre, double-blind randomised study. Ann Rheum Dis 70:1905鈥?913 CrossRef
  28. Furie R, Nicholls K, Cheng TT et al (2014) Efficacy and safety of abatacept in lupus nephritis: a twelve-month, randomized, double-blind study. Arthritis Rheumatol 66:379鈥?89 CrossRef
  29. Shirota Y, Yarboro C, Fischer R et al (2013) Impact of anti-interleukin-6 receptor blockade on circulating T and B cell subsets in patients with systemic lupus erythematosus. Ann Rheum Dis 72:118鈥?28 CrossRef
  30. Norby GE, Holme I, Fellstr枚m B et al (2009) Effect of fluvastatin on cardiac outcomes in kidney transplant patients with systemic lupus erythematosus: a randomized placebo-controlled study. Arthritis Rheum 60(4):1060鈥?064 CrossRef
  
• 作者单位：PD Dr. K. Tenbrock (1)
  
  1. Klinik f眉r Kinder und Jugendmedizin, Abteilung P盲diatrische Rheumatologie, Division of Pediatric Pneumology, Allergology and Immunology, Klinikum der RWTH Aachen, RWTH Aachen, University, Pauwelsstr. 30, 52074, Aachen, Deutschland
  
• ISSN：1435-1250

文摘

Background Systemic lupus erythematosus is a complex autoimmune disease that can affect multiple organs and is characterized by a loss of peripheral tolerance against nuclear antigens, pathogenic B and T cell responses and production of autoantibodies. The prevalence is estimated to be 40 per 100,000 in the population in Europe but can be as high as 150 patients per 100,000 among the Afro-Caribbean population. Although the 5-year survival rate in the 1950s was estimated to be only 50鈥?, the 10-year survival rate is currently estimated to be 70鈥?2鈥?. This progress is particularly due to a better understanding of the pathogenesis that opened up better therapeutic possibilities in the past and now raises new perspectives for future therapy approaches. Objective The current knowledge on the pathogenesis and the current situation of new therapeutic approaches for SLE are presented. Results and discussion This progress in the therapeutic options was made possible by a better understanding of the pathophysiology, which leads to the expectation of an improvement in the prognosis of patients due to reduction in the burden of the disease in the future. Several new therapeutic medications are currently awaiting approval and recently for the first time in more than 50 years a new medication for SLE was approved, a monoclonal antibody to the tumor necrosis factor (TNF)-like ligand, B-cell activating factor (BAFF) belonging to the TNF family also named B-cell lymphocyte stimulator (BLyS), BAFF/BLyS.