The applied basic research of systemic lupus erythematosus based on the biological omics

Genes and Immunity

Volumn 14, Issue 3, 2013, Pages 133-146

  Sui, W ^a   Hou, X ^a,b   Che, W ^a   Yang, M ^a   Dai, Y ^a,c  

^a Central Laboratory of Guilin 181st Hospital   (China)

^b GUANGXI NORMAL UNIVERSITY   (China)

^c SHENZHEN PEOPLE'S HOSPITAL   (China)

Author keywords

biological omics; pathogenesis; systemic lupus erythematosus

Indexed keywords

ALPHA INTERFERON; C REACTIVE PROTEIN; CD16 ANTIGEN; CD9 ANTIGEN; COMPLEMENT COMPONENT C1Q; CYTOKERATIN; FIBROBLAST GROWTH FACTOR 8; GELATINASE B; HLA ANTIGEN; HLA ANTIGEN CLASS 2; INTERFERON REGULATORY FACTOR 5; INTERFERON REGULATORY FACTOR 7; INTERLEUKIN 10; MESSENGER RNA; MICRORNA; NON RECEPTOR PROTEIN TYROSINE PHOSPHATASE 22; PROGRAMMED DEATH 1 RECEPTOR; STAT1 PROTEIN; STAT4 PROTEIN; TRANSCRIPTION FACTOR FKHRL1; TRANSCRIPTION FACTOR SOX5; TUMOR NECROSIS FACTOR ALPHA;

3' UNTRANSLATED REGION; ALLELE; CD4+ T LYMPHOCYTE; DEAD BOX POLYPEPTIDE 6; DNA METHYLATION; EPIGENETICS; HAPLOTYPE; HUMAN; MEDICAL RESEARCH; METABOLOMICS; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN MODIFICATION; PROTEIN PROCESSING; PROTEOMICS; REVIEW; SINGLE NUCLEOTIDE POLYMORPHISM; SYSTEMIC LUPUS ERYTHEMATOSUS;

DNA METHYLATION; GENOMICS; HUMANS; LUPUS ERYTHEMATOSUS, SYSTEMIC; METABOLOMICS; MODELS, GENETIC; MODELS, IMMUNOLOGICAL; PROTEIN PROCESSING, POST-TRANSLATIONAL; PROTEOMICS; TRANSCRIPTOME;

EID: 84876894882     PISSN: 14664879     EISSN: 14765470     Source Type: Journal    
DOI: 10.1038/gene.2013.3     Document Type: Review

References (181)

1. Bengtsson AA, Rylander L, Hagmar L, Nived O, Sturfelt G. Risk factors for developing systemic lupus erythematosus: a case-control study in Southern Sweden. Rheumatology 2002; 41: 563-571. (Pubitemid 34567188)
2. Cheong HS, Lee SO, Choi CB, Sung YK, Shin HD, Bae1 SC. MERTK polymorphisms associated with risk of haematological disorders among Korean SLE patients. Rheumatology 2007; 46: 209-214. (Pubitemid 46189777)
3. Lopez-Nevot MA, Ramal L, Jimenez-Alonso J, Martn J. The inducible nitric oxide synthase promoter polymorphism does not confer susceptibility to systemic lupus erythematosus. Rheumatology 2003; 42: 113-116. (Pubitemid 36142012)
4. Villarreal J, Crosdale D, Ollier W. Mannose binding lectin and Fc gamma RIIa (CD32) polymorphism in Spanish systemic lupus erythematosus patients. Rheumatology 2001; 40: 1009-1012.
5. Tsao BP, Wu H. The genetics of human lupus. In: Wallace DJ, Hahn BH (eds) Dubois' lupus erythematosus. 7th edn Lippincott Williams & Wilkins: Philadelphia, 2007, pp 54-81.
6. Harley JB, Alarco n-Riquelme ME, Criswell LA. Genome-wide association scan in women with systemic lupus erythematosus identifies susceptibility variants in ITGAM, PXK, KIAA1542 and other loci. Nat Genet 2008; 40: 204-210. (Pubitemid 351171405)
7. Fernando MM, Stevens CR, Sabeti PC, Walsh EC, McWhinnie AJ, Shah A et al. Identification of two independent risk factors for lupus within the MHC in United Kingdom families. Plos Genet 2007; 3: e192.
8. Yang W, Shen N, Ye DQ. Genome-wide association study in Asian populations identifies variants in ETS1 and WDFY4 associated with systemic lupus erythematosus. PLoS Genet 2010; 6: e1000841.
9. Slingsby JH, Norsworthy P, Pearce G. Homozygous hereditary C1q deficiency and systemic lupus erythematosus. A new family and the molecular basis of C1q deficiency in three families. Arthritis Rheum 1996; 39: 663-670. (Pubitemid 26118046)
10. Barilla-LaBarca ML, Atkinson JP. Rheumatic syndromes associated with complement deficiency. Curr Opin Rheumatol 2003; 15: 55-60. (Pubitemid 36021024)
11. Wu YL. Phenotypes, genotypes and disease susceptibility associated with gene copy number variations: complement C4 CNVs in European American healthy subjects and those with systemic lupus erythematosus. Cytogenet Genome Res 2009; 123: 131-141.
12. Salmon JE, Pricop L. Human receptors for immunoglobulin G: key elements in the pathogenesis of rheumatic disease. Arthritis Rheum 2001; 44: 739-750. (Pubitemid 32319766)
13. Salmon JE, Millard S, Schachter LA, Arnett FC, Ginzler EM, Gourley MF et al. FcgammaRIIA alleles are heritable risk factors for lupus nephritis in African Americans. J Clin Invest 1996; 97: 1348-1354. (Pubitemid 26085492)
14. Chu ZT, Tsuchiya N, Kyogoku C. Association of Fcgamma receptorIIb polymorphism with susceptibility to systemic lupus erythematosus in Chinese: a common susceptibility gene in the Asian population. Tissue Antigens 2004; 63: 21-27. (Pubitemid 38130438)
15. Kyogoku C, Dijstelbloem HM, Tsuchiya N, Hatta Y, Kato1 H, Yamaguchi1 A et al. Fcgamma receptor gene polymorphisms in Japanese patients with systemic lupus erythematosus: contribution of FCGR2B to gene susceptibility. Arthritis Rheum 2002; 46: 1242-1254. (Pubitemid 34525832)
16. Siriboonrit U, Tsuchiya N, Sirikong M. Association of Fcgamma receptor IIb and IIIb polymorphisms with susceptibility to systemic lupus erythematosus in Thais. Tissue Antigens 2003; 61: 374-383. (Pubitemid 36605670)
17. Li X, Wu J, Carter RH. A novel polymorphism in the Fcgamma receptor IB(CD32B) transmembrane region alters receptor signaling. Arthritis Rheum 2003; 48: 3242-3252. (Pubitemid 37409339)
18. Magnusson V, Zunec R, Odeberg J, Sturfelt G, Truedsson L, Gunnarsson I et al. Polymorphisms of the Fcgamma receptor type Ib gene are not associated with systemic lupus erythematosus in the Swedish population. Arthritis Rheum 2004; 50: 1348-1350. (Pubitemid 38480847)
19. Su K, Wu J, Edberg JC. A promoter haplotype of the immunoreceptor tyrosine-based inhibitory motif-bearing Fcgamma RIIb alters receptor expression and associates with autoimmunity. I. Regulatory FCGR2B polymorphisms and their association with systemic lupus erythematosus. J Immunol 2004; 172: 7186-7191. (Pubitemid 38669163)
20. Su K, Li X, Edberg JC. A promoter haplotype of the immunoreceptor tyrosinebased inhibitory motif-bearing FcgammaRIIb alters receptor expression and associates with autoimmunity. II. Differential binding of GATA4 and Yin-Yang1 transcription factors and correlated receptor expression and function. J Immunol 2004; 172: 7192-7199. (Pubitemid 38669164)
21. Karassa FB. The Fcg RIIIA-F158 allele is a risk factor for the development of lupus nephritis: a meta-Analysis. Kidney Int 2003; 63: 1475-1482. (Pubitemid 36350013)
22. Salmon JE, Edberg JC, Kimberly RP. Fcgamma receptor III on human neutrophils Allelic variants have functionally distinct capacities. J Clin Invest 1990; 85: 1287-1295. (Pubitemid 20123776)
23. Hooks JJ, Moutsopoulos HM, Geis SA, Stahl NI, Decker JL, Notkins AL. Immune interferon in the circulation of patients with autoimmune disease. N Engl J Med 1979; 301: 5-8. (Pubitemid 9226519)
24. Takahashi S, Fossati L, Iwamoto M, Iwamoto R, Motta R, Kobayakawa T et al. Imbalance towards Th1 predominance is associated with acceleration of lupuslike autoimmune syndrome in MRL mice. J Clin Invest 1996; 97: 1597-1604. (Pubitemid 26105469)
25. Graham RR, Kozyrev SV, Baechler EC, Reddy MV, Plenge1 RM, Bauer JW et al. A common haplotype of interferon regulatory factor 5 (IRF5) regulates splicing and expression and is associated with increased risk of systemic lupus erythematosus. Nat Genet 2006; 38: 550-555.
26. Graham RR, Kyogoku C, Sigurdsson S. Three functional variants of IFN regulatory factor 5 (IRF5) define risk and protective haplotypes for human lupus. Proc Natl Acad Sci USA 2007; 104: 6758-6763. (Pubitemid 47175574)
27. Siu HO, Yang W, Lau CS. Association of a haplotype of IRF5 gene with systemic lupus erythematosus in chinese. J Rheumatol 2008; 35: 360-362. (Pubitemid 351281165)
28. Kelly JA, Kelley JM, Kaufman KM, Kilpatrick J, Bruner1 GR, Merrill JT et al. Interferon regulatory factor-5 is genetically associated with systemic lupus erythematosus in African Americans. Genes Immun 2008; 9: 187-194. (Pubitemid 351584185)
29. Lofgren SE, Yin H, Delgado-Vega AM. Promoter insertion/deletion in the IRF5 gene is highly associated with susceptibility to systemic lupus erythematosus in distinct populations, but exerts a modest effect on gene expression in peripheral blood mononuclear cells. J Rheumatol 2010; 37: 574-578.
30. Hikami K, Kawasaki A, Ito I. Association of a functional polymorphism in the 3'-untranslated region of SPI1 with systemic lupus erythematosus. Arthritis Rheum 2011; 63: 755-763.
31. Yee AA, Yin P, Siderovski DP, Mak1 TW, Litchfield DW, Arrowsmith CH. Cooperative interaction between the DNA-binding domains of PU.1 and IRF4. J Mol Biol 1998; 279: 1075-1083. (Pubitemid 28302385)
32. Huang W, Horvath E, Eklund EA. PU.1, interferon regulatory factor (IRF) 2, and the interferon consensus sequence-binding protein (ICSBP/IRF8) cooperate to activate NF1 transcription in differentiating myeloid cells. J Biol Chem 2007; 282: 6629-6643. (Pubitemid 47100819)
33. Zhang L, Pagano JS. Structure and function of IRF-7. J Interferon Cytokine Res 2002; 22: 95-101. (Pubitemid 34161287)
34. Taylor KE, Remmers EF, Lee AT, Ortmann WA, Plenge RM, Tian C et al. Specificity of the STAT4 genetic association for severe disease manifestations of systemic lupus erythematosus. PLoS Genet 2008; 4: e1000084.
35. Kariuki SN, Kirou KA, MacDermott EJ. Cutting edge: autoimmune disease risk variant of STAT4 confers increased sensitivity to IFN-A in lupus patients in vivo. J Immunol 2009; 182: 34-38.
36. Dunham I, Sargent CA, Trowsdale J, Campbell RD. Molecular mapping of the human major histocompatibility complex by pulsed-field gel electrophoresis. Proc Natl Acad Sci USA 1987; 84: 7237-7241.
37. Vassalli P. The pathophysiology of tumor necrosis factors. Annu Rev Immunol 1992; 10: 411-452.
38. Allen RD. Polymorphism of the human TNF-Alpha promoter-random variation or functional diversity. Mol Immunol 1999; 36: 1017-1027. (Pubitemid 30078905)
39. Bouma G, Crusius JB, Oudkerk Pool M, Kolkman JJ, von Blomberg BM, Kostense PJ et al. Secretion of tumour necrosis factor alpha and lymphotoxin alpha in relation to polymorphisms in the TNF genes and HLA-DR alleles. Relevance for inflammatory bowel disease. Scand J Immunol 1996; 43: 456-463. (Pubitemid 26104933)
40. Lee YH, Harley JB, Nath SK. Meta-Analysis of TNF-Alpha promoter-308A/G polymorphism and SLE susceptibility. Eur J Hum Genet 2006; 14: 364-371.
41. Lopez P, Gutierrez C, Suare A. IL-10 and TNFa genotypes in SLE. J Biomed Biotechnol 2010; 2010: 838390.
42. Yap DYH, Lai KN. Cytokines and their roles in the pathogenesis of systemic lupus erythematosus: from basics to recent advances. J Biomed Biotechnol 2010; 2010: 365083.
43. Graham DSC, Graham RR, Manku H, Wong AK, Whittaker JC, Gaffney PM et al. Polymorphism at the TNF superfamily gene TNFSF4 confers susceptibility to systemic lupus erythematosus. Nat Genet 2008; 40: 83-89.
44. Bates JS, Lessard CJ, Leon JM, Nguyen T, Battiest LJ, Rodgers J et al. Meta-Analysis and imputation identifies a 109kb risk haplotype spanning TNFAIP3 associated with lupus nephritis and hematologic manifestations. Genes Immun 2009; 10: 470-477.
45. Musone SL, Taylor KE, Lu TT, Nititham J, Ferreira RC, Ortmann W et al. Multiple polymorphisms in the TNFAIP3 region are independently associated with systemic lupus erythematosus. Nat Genet 2008; 40: 1062-1064.
46. Han JW, Zheng HF, Cui Y, Nititham J, Ferreira RC, Ortmann W et al. Genome-wide association study in a Chinese Han population identifies nine new susceptibility loci for systemic lupus erythematosus. Nat Genet 2009; 41: 1234-1237.
47. Gateva V, Sandling JK, Hom G, Taylor KE, Chung SA, Sun X et al. A large-scale replication study identifies TNIP1, PRDM1, JAZF1, UHRF1BP1 and IL10 as risk loci for systemic lupus erythematosus. Nat Genet 2009; 41: 1228-1233.
48. Tokano Y, Morimoto S, Kaneko H, Amano H, Nozawa K, Takasaki Y et al. Levels of IL-12 in the sera of patients with systemic lupus erythematosus (SLE)-relation to Th1-And Th2-derived cytokines. Clin Exp Immunol 1999; 116: 169-173. (Pubitemid 29170021)
49. Calvani N, Richards HB, Tucci M, Pannarale G, Silvestris F. Up-regulation of IL-18 and predominance of a Th1 immune response is a hallmark of lupus nephritis. Clin Exp Immunol 2004; 138: 171-178. (Pubitemid 39279981)
50. Nishimura H, Honjo T. PD-1: an inhibitory immunoreceptor involved in peripheral tolerance. Trends Immunol 2001; 22: 265-268. (Pubitemid 32667515)
51. Prokunina L, Castillejo-Lopez C, Oberg F, Gunnarsson I, Berg L, Magnusson V et al. A regulatory polymorphism in PDCD1 is associated with susceptibility to systemic lupus erythematosus in humans. Nat Genet 2002; 32: 666-669. (Pubitemid 35435182)
52. Hiromine Y, Ikegami H, Fujisawa T, Nojima K, Kawabata Y, Nosoa S et al. Trinucleotide repeats of programmed cell death-1 gene are associated with susceptibility to type 1 diabetes mellitus. Metabolism 2007; 56: 905-909. (Pubitemid 46890972)
53. Sanghera DK, Manzi S, Bontempo F. Role of an intronic polymorphism in the PDCD1 gene with the risk of sporadic systemic lupus erythematosus and the occurrence of antiphospholipid antibodies. Hum Genet 2004; 115: 393-398. (Pubitemid 39341713)
54. Nielsen C, Hansen D, Husby S, Jacobsen BB, Lillevang ST. Association of a putative regulatory polymorphism in the PD-1 gene with susceptibility to type 1 diabetes. Tissue Antigens 2003; 62: 492-497. (Pubitemid 37479307)
55. Kroner A, Mehling M, Hemmer B, Rieckmann P, Toyka KV, Maurer M et al. A PD-1 polymorphism is associated with disease progression in multiple sclerosis. Ann Neurol 2005; 58: 50-57. (Pubitemid 40962460)
56. Carroll M. The complement system in regulation of adaptive immunity. Nat Immunol 2004; 5: 981-986. (Pubitemid 41057714)
57. Marnell L, Mold C, Du Clos T. C-reactive protein: ligands, receptors and role in inflammation. Clin Immunol 2005; 117: 104-111. (Pubitemid 41407719)
58. Crawford D, Sanders C, Qin X, Smith J, Shephard C, Wong M et al. Genetic variation is associated with C-reactive protein levels in the Third National Health and Nutrition Examination Survey. Circulation 2006; 114: 2458-2465. (Pubitemid 44901518)
59. Carlson C, Aldred S, Lee P, Tracy R, Schwartz S, Rieder M et al. Polymorphisms within the C-reactive protein (CRP) promoter region are associated with plasma CRP levels. Am J Hum Genet 2005; 77: 64-77. (Pubitemid 40848037)
60. Gregersen PK. Gaining insight into PTPN22 and autoimmunity. Nat Genet 2005; 37: 1300-1302. (Pubitemid 41722179)
61. Bottini N, Musumeci L, Alonso A, Rahmouni S, Nika K, Rostamkhani M et al. A functional variant of lymphoid tyrosine phosphatase is associated with type I diabetes. Nat Genet 2004; 36: 337-338. (Pubitemid 38437254)
62. Zhang JY, Zahir N, Jiang QH, Miliotis H, Heyraud S, Meng XW et al. The autoimmune disease-Associated PTPN22 variant promotes calpain-mediated Lyp/Pep degradation associated with lymphocyte and dendritic cell hyperresponsiveness. Nat Genet 2011; 43: 902-907.
63. Arechiga AF, Habib T, He YT, Zhang X, Zhang ZY, Funk A et al. Cutting edge: The PTPN22 allelic variant associated with autoimmunity impairs B cell signaling. J Immunol 2009; 182: 3343-3347.
64. Menard L, Saadoun D, Isnardi I, Ng YS, Meyers G, Massad C et al. The PTPN22 allele encoding an R620W variant interferes with the removal of developing autoreactive B cells in humans. J Clin Invest 2011; 121: 3635-3644.
65. Zikherman JL, Hermiston M, Steiner D, Hasegawa K, Chan A, Weiss A et al. PTPN22 deficiency cooperates with the CD45 E613R allele to break tolerance on a non-Autoimmune background. J Immunol 2009; 182: 4093-4106.
66. Mori M, Yamada R, Kobayashi K, Kawaida R, Yamamoto K. Ethnic differences in allele frequency of autoimmune-disease-Associated SNPs. J Hum Genet 2005; 50: 264-266. (Pubitemid 40922327)
67. Gregersen PK, Lee HS, Batliwalla F, Begovich AB. PTPN22: setting thresholds for autoimmunity. Semin Immunol 2006; 18: 214-223. (Pubitemid 43903284)
68. Pradhan V, Borse V, Ghosh K. PTPN22 gene polymorphisms in autoimmune diseases with special reference to systemic lupus erythematosus disease susceptibility. J Postgrad Med 2010; 56: 239-242.
69. Aksoy R, Duman T, Keskin O, Du zgun N. No association of PTPN22 R620W gene polymorphism with rheumatic heart disease and systemic lupus erythematosus. Mol Biol Rep 2011; 38: 5393-5396.
70. Orru V, Tsai SJ, Rueda B, Fiorillo E, Stanford SM, Dasgupta J et al. A loss-offunction variant of PTPN22 is associated with reduced risk of systemic lupus erythematosus. Hum Mol Genet 2009; 18: 569-579.
71. Manjarrez-Orduno N, Marasco E, Chung SA, Katz MS, Kiridly JF, Simpfendorfer KR et al. CSK regulatory polymorphism is associated with systemic lupus erythematosus and influences B-cell signaling and activation. Nat Genet 2012; 44: 1227-1230.
72. Suggs MJ, Majithiab V, Lewisa RE, Cruse JM. HLA DRB*1503 allelic haplotype predominance and associated immunodysregulation in systemic lupus erythematosus. Exp Mol Pathol 2011; 91: 548-562.
73. Hedrich CM. Genetic variation and epigenetic patterns in autoimmunity. J Genet Syndr Gene Ther. 2:0e2. doi:10.4172/2157-7412.10000e2.
74. Renaudineau Y, Youinou P. Epigenetics and autoimmunity with special emphasis on methylation. Keio J Med 2011; 60: 10-16.
75. Richardson B, Scheinbart L, Strahler J, Gross L, Hanash S, Johnson M. Evidence for impaired T cell DNA methylation in systemic lupus erythematosus and rheumatoid arthritis. Arthritis Rheum 1990; 33: 1665-1673.
76. Corvetta A, Bitta RD, Luchetti MM, Pomponio G. 5-Methylcytosine content of DNA in blood, synovial mononuclear cells and synovial tissue from patients affected by autoimmune rheumatic diseases. J Chromatogr 1991; 566: 481-491.
77. Hedrich CM, Tsokos GC. Epigenetic mechanisms in systemic lupus erythematosus and other autoimmune diseases. Trends Mol Med 2011; 12: 714-724.
78. Zouali M. Epigenetics in lupus. Ann NY Acad Sci 2011; 1217: 154-165.
79. Jeffries MA, Dozmorov M, Tang Y, Merrill JT, Wren JD, Sawalha AH. Genomewide DNA methylation patterns in CD4\+ T cells from patients with systemic lupus erythematosus. Epigenetics 2011; 6: 593-601.
80. Rai K, Huggins IJ, James SR, Karpf AR, Jones DA, Cairns BR. DNA demethylation in zebrafish involves the coupling of a deaminase, a glycosylase, and gadd45. Cell 2008; 135: 1201-1212.
81. Zhao M, Sun YM, Gao F, Wu XY, Tang JL, Yin H et al. Epigenetics and SLE: RFX1 downregulation causes CD11a and CD70 overexpression by altering epigenetic modifications in lupus CD4\+T cells. J Autoimmun 2010; 35: 58-69.
82. Dieker J, Muller S. Epigenetic histone code and autoimmunity. Clin Rev Allergy Immunol 2010; 39: 78-84.
83. Dai Y, Zhang L, Hu C, Zhang Y. Genome-wide analysis of histone H3 lysine 4 trimethylation by ChIP-chip in peripheral blood mononuclear cells of systemic lupus erythematosus patients. Clin Exp Rheumatol 2010; 28: 158-168.
84. Clayton AL, Hazzalin CA, Mahadevan LC. Enhanced histone acetylation and transcription: a dynamic perspective. Mol Cell 2006; 23: 289-296. (Pubitemid 44128853)
85. Zhang Z, Song L, Maurer K, Petri MA, Sullivan KE. Global H4 acetylation analysis by ChIP-chip in systemic lupus erythematosus monocytes. Genes Immun 2010; 11: 124-133.
86. Forster N, Gallinat S, Jablonska J, Weiss S, Elsasser HP, Lutz W. p300 protein acetyltransferase activity suppresses systemic lupus erythematosus-like autoimmune disease in mice. J Immunol 2007; 178: 6941-6948. (Pubitemid 46847420)
87. Dieker JW, Fransen JH, van Bavel CC, Briand JP, Jacobs CW, Muller S et al. Apoptosis-induced acetylation of histones is pathogenic in systemic lupus erythematosus. Arthritis Rheum 2007; 56: 1921-1933. (Pubitemid 47110391)
88. Flynt AS, Lai EC. Biological principles of microRNA-mediated regulation: shared themes amid diversity. Nat Rev Genet 2008; 9: 831-842.
89. Baltimore D, Boldin MP, O'Connell RM, Rao DS, Taganov KD. MicroRNAs: new regulators of immune cell development and function. Nat Immunol 2008; 9: 839-845. (Pubitemid 352038302)
90. Tang Y, Luo X, Cui H, Ni X, Yuan M, Guo Y et al. MicroRNA-146A contributes to abnormal activation of the type I interferon pathway in human lupus by targeting the key signaling proteins. Arthritis Rheum 2009; 60: 1065-1075.
91. Te JL, Dozmorov IM, Guthridge JM, Nguyen KL, Cavett JW, Kelly JA et al. Identification of unique microRNA signature associated with lupus nephritis. PLoS One 2010; 5: e10344.
92. Dai Y, Huang YS, Tang M, Lv TY, Hu CX, Tan YH et al. Microarray analysis of microRNA expression in peripheral blood cells of systemic lupus erythematosus patients. Lupus 2007; 16: 939-946.
93. Dai Y, Sui WG, Lan HJ, Yan Q, Huang H, Huang YS. Comprehensive analysis of microRNA expression patterns in renal biopsies of lupus nephritis patients. Rheumatol Int 2009; 29: 749-754.
94. Elias Stagakis GB, Panayotis V. Identification of novel microRNA signatures linked to human lupus disease activity and pathogenesis: miR-21 regulates aberrant T cell responses through regulation of PDCD4 expression. Ann Rheum Dis 2011; 70: 1496-1506.
95. Zhao X, Tang Y, Qu B, Cui H, Wang S, Wang L et al. MicroRNA-125a contributes to elevated inflammatory chemokine RANTES levels via targeting KLF13 in systemic lupus erythematosus. Arthritis Rheum 2010; 62: 3425-3435.
96. Zhao S, Wang Y, Liang Y, Zhao M, Long H, Ding S et al. MicroRNA-126 regulates DNA methylation in CD4\+ T cells and contributes to systemic lupus erythematosus by targeting DNA methyltransferase 1. Arthritis Rheum 2011; 63: 1376-1386.
97. Ding S, Liang YS, Zhao M, Liang GP, Long H, Zhao S et al. Decreased miR-142-3p/5p expression causes CD4\+ T cell activation and B cell hyperstimulation in systemic lupus erythematosus. Arthritis Rheum 2012; 64: 2953-2963.
98. Venter JC, Adams MD, Myers EW, Li PW, Mural RJ, Sutton GG et al. The sequence of the human genome. Science 2001; 291: 1304-1352.
99. Matthias P, Rolink AG. Transcriptional networks in developing and mature B cells. Nat Rev Immunol 2005; 5: 497-508. (Pubitemid 40835037)
100. Kawai T, Akira S. TLR signaling. Cell Death Differ 2006; 13: 816-825.
101. Sui WG, Lin H, Chen JJ, Ou ML, Dai Y. Comprehensive analysis of transcription factor expression patterns in peripheral blood mononuclear cell of systemic lupus erythematosus. Int J Rheum Dis 2012; 15: 212-219.
102. Kuo CC, Lin SC. Altered FOXO1 transcript levels in peripheral blood mononuclear cells of systemic lupus erythematosus and rheumatoid arthritis patients. Mol Med 2007; 13: 561-566.
103. Burgos P, Metz C, Bull P, Pincheira R, Massardo L, Erra zuriz C et al. Increased expression of c-rel, from the NF-KB/Rel family, in T cells from patients with systemic lupus erythematosus. J Rheumatol 2000; 27: 116-127. (Pubitemid 30058638)
104. Dai RJ, Phillips RA, Karpuzoglu E. Estrogen regulates transcription factors STAT-1 and NF-kB to promote inducible nitric oxide synthase (iNOS) and inflammatory responses. J Immunol 2009; 183: 6998-7005.
105. Foster MH, Kelley VR. Lupus nephritis: update on pathogenesis and disease mechanisms. Semin Nephrol 1999; 19: 173-181. (Pubitemid 29132016)
106. Lit LC, Wong CK, Li EK, Tam LS, Lam CW, Lo YM. Elevated gene expression of Th1/Th2 associated transcription factors is correlated with disease activity in patients with systemic lupus erythematosus. J Rheumatol 2007; 34: 89-96. (Pubitemid 46106567)
107. Chan RW, Lai FM, Li EK, Tan LS, Chow KM, Li PK et al. Imbalance of Th1/Th2 transcription factors in patients with lupus nephritis. Rheumatology 2006; 45: 951-957. (Pubitemid 44283048)
108. Remoli ME, Ragimbeau J, Giacomini E, Gafa V, Severa M, Lande R et al. NF-{kappa}B is required for STAT-4 expression during dendritic cell maturation. J Leukoc Biol 2007; 81: 355-363. (Pubitemid 46021286)
109. Kyttaris VC, Wang Y, Juang YT, Weinstein A, Tsokos GC. Increased Levels of NF-ATc2 differentially regulate CD154 and IL-2 genes in T cells from patients with systemic lupus erythematosus. J Immunol 2007; 178: 1960-1966. (Pubitemid 46154669)
110. Westphal RS, Anderson KA, Means AR, Wadzinski BE. A signaling complex of Ca2\+ calmodulin-dependent protein kinase IV and protein phosphatase 2A. Science 1998; 280: 1258-1261.
111. Juang YT, Rauen T, Wang Y, Ichinose K, Benedyk K, Tenbrock K et al. Transcriptional activation of the cAMP-responsive modulator promoter in human T cells is regulated by protein phosphatase 2A-mediated dephosphorylation of SP-1 and reflects disease activity in patients with systemic lupus erythematosus. J Biol Chem 2011; 286: 1795-1801.
112. Tenbrock K, Juang YT, Tolnay M, Tsokos GC. The cyclic adenosine 5'-monophosphate response element modulator suppresses IL-2 production in stimulated T cells by a chromatin-dependent mechanism. J Immunol 2003; 170: 2971-2976. (Pubitemid 36302169)
113. Levanon E, Eisenberg E, Yelin R, Nemzer S, Hallegger M, Shemesh R et al. Systematic identification of abundant A-to-I editing sites in the human transcriptome. Nat Biotechnol 2004; 22: 1001-1005. (Pubitemid 39014477)
114. Laxminarayana D, Khan IU, Kammer GM. Transcript mutations of the alpha regulatory subunit of protein kinase A and up-regu-lation of the RNA editing gene transcripts in lupus T lympho-cytes. Lancet 2002; 360: 842-849. (Pubitemid 35257948)
115. Toyabe S, Kaneko U, Uchiyama M. Decreased DAP12 expression in natural killer lymphocytes from patients with systemic lupus erythematosus is associated with increased transcript mutations. J Autoimmun 2004; 23: 371-378. (Pubitemid 39574812)
116. Laxminarayana D, Khan IU, Kammer MG. Transcript mutations of the regulatory subunit of protein kinase A and up-regulation of the RNA-editing gene transcript in lupus T lymphocytes. Lancet 2002; 360: 842-849. (Pubitemid 35257948)
117. Laxminarayana D, Kammer MG. mRNA mutations of type 1 protein kinase A regulatory subunitasubject with systemic lupus erythematosus. Int Immunol 2000; 12: 1521-1529.
118. Laxminarayana D, O'Rourke KS, Maas S, Olorenshaw I. Altered editing in RNA editing adenosine deaminase ADAR2 gene transcripts of systemic lupus erythematosus T lymphocytes. Immunology 2007; 121: 359-369. (Pubitemid 46817357)
119. Orlowski RJ, O'Rourke KS, Olorenshaw I, Hawkins GA, Maas S, Laxminarayana D. Altered editing in cyclic nucleotide phosphodiesterase 8A1 gene transcripts of systemic lupus erythematosus T lymphocytes. Immunology 2008; 125: 408-419.
120. Wu JM, Xie FL, Qian K, Gibson AW, Edberg JC, Kimberly RP. FAS mRNA editing in human systemic lupus erythematosus. Hum Mutat 2011; 32: 1268-1277.
121. Laxminarayana D, Khan IU, O'Rourke KS, Giri B. Induction of 150 kDa adenosine deaminase that acts on RNA (ADAR1) gene expression in normal T lymphocytes by physiological activation. Immunology 2007; 122: 623-633. (Pubitemid 350075962)
122. Khan IU, Wallin R, Gupta RS, Kammer GM. Protein kinase A-catalyzed its attachment to histone 2B in the T lymphocyte plasma membrane. Proc Natl Acad Sci USA 1998; 95: 10425-10430.
123. Chen DS, Pace PE, Coombes RC, Ali S. Phosphorylation of human estrogen receptor alpha by protein kinase A regulation dimerization. Mol Cell Biol 1999; 19: 1002-1015. (Pubitemid 29046844)
124. Yamamoto KK, Gonzalez GA, Biggs WH, Montminy MR. Phosphorylation-induced binding and transcriptional efficacy of nuclear factor CREB. Nature 1998; 334: 494-498.
125. Brunner T, Mogil RJ, LaFace D, Yoo NJ, Mahboubi A, Echeverri F et al. Cellautonomous FAS (CD95)/FAS-ligand interaction mediates activation-induced apoptosis in T-cell hybridomas. Nature 1995; 373: 441-444.
126. Johnson JM, Castle J, Garrett-Engele P, Kan Z, Loerch PM, Armour CD et al. Genome-wide survey of human alternative pre-mRNA splicing with exon junction microarrays. Science 2003; 302: 2141-2144. (Pubitemid 38017950)
127. Moulton VR, Tsokos GC. Alternative splicing factor/splicing factor 2 regulates the expression of the z subunit of the human T cell receptor-Associated CD3 complex. J Biol Chem 2010; 285: 12490-12496.
128. Nambiar MP, Enyedy EJ, Warke VG, Krishnan S, Dennis G, Kammer GM et al. Polymorphisms/mutations of TCR-zeta-chain promoter and 3' untranslated region and selective expression of TCR zeta-chain with an alternatively spliced 3' untranslated region in patients with systemic lupus erythematosus. J Autoimmun 2001; 16: 133-142. (Pubitemid 32552988)
129. Chowdhury B, Tsokos CG, Krishnan S, Robertson J, Fisher CU, Warke RG et al. Decreased stability and translation of T cell receptor zeta mRNA with an alternatively spliced 3'-untranslated region contribute to zeta chain down-regulation in patients with systemic lupus erythematosus. J Biol Chem 2005; 280: 18959-18966. (Pubitemid 41379599)
130. Tenbrock K, Juang YT, Gourley MF, Nambiar MP, Tsokos GC. Antisense cyclic adenosine 5'-monophosphate response element modulator up-regulates IL-2 in T cells from patients with systemic lupus erythematosus. J Immunol 2002; 169: 4147-4152. (Pubitemid 35178184)
131. Li Y, Harada T, Juang YT, Kyttaris VC, Wang Y, Zidanic M et al. Phosphorylated ERM is responsible for increased T cell polarization, adhesion, and migration in patients with systemic lupus erythematosus. J Immunol 2007; 178: 1938-1947. (Pubitemid 46154667)
132. Chen ZC. Advances in cancer proteomics study. Ai Zheng 2004; 23: 113-117.
133. Dai Y, Hu C, Huang Y, Huang HY, Liu J, Lv T. A proteomic study of peripheral blood mononuclear cells in systemic lupus erythematosus. Lupus 2008; 17: 799-804.
134. Wang LQ, Dai Y, Qi SW, Sun B, Wen JL, Zhang L et al. Comparative proteome analysis of peripheral blood mononuclear cells in systemic lupus erythematosus with iTRAQ quantitative proteomics. Rheumatol Int 2012; 32: 585-593.
135. Wang L, Dai Y, Peng W, Qi S, Ouyang X, Tu Z. Differential expression of serinethreonine kinase receptor-Associated protein in patients with systemiclupus erythematosus. Lupus 2011; 20: 921-927.
136. Huang ZC, Shi YY, Cai B, Wang LL, Wu YK, Ying BW et al. Promising diagnostic model for systemic lupus erythematosus using proteomic fingerprint technology. J Sichuan Univ (Med Sci Edi) V 2009; 40: 499-503.
137. Dai Y, Hu C, Wang L, zhang L, xiao X, Tan Y. Serum peptidome patients of human systemic lupus erythematosus based on magnetic bead separation and MALDI-TOF mass spectrometry analysis. Scand J Rheumatol 2010; 39: 240-246.
138. Mosley K, Tam FWK, Edwards RJ, Crozier J, Pusey CD, Lightstone L. Urinary proteomic profiles distinguish between active and inactive SLE nephritis. Rheumatology 2006; 45: 1497-1504. (Pubitemid 44817055)
139. Suzuki M, Ross GF, Wiers K, Nelson S, Bennett M, Passo MH et al. Identification of a urinary proteomic signature for lupus nephritis in children. Pediatr Nephrol 2007; 22: 2047-2057. (Pubitemid 350090711)
140. Zhang XL, Jin M, Wu HF, Nadasdy T, Nadasdy G, Harris N et al. Biomarkers of lupus nephritis determined by serial urine proteomics. Kidney Int 2008; 74: 799-807.
141. Anderton BH. Intermediate filaments: a family of homologous structures. J Muscle Res Cell Motil 1981; 2: 141-166.
142. Watanabe S, Wagatsuma K, Ichikawa E, Takahashi H. Abnormal distribution of epidermal protein antigens in psoriatic epidermis. J Dermatol 1991; 18: 143-151.
143. Watanabe S, Wagatsuma K, Takahashi H. Immunohistochemical localization of cytokeratins and involucrin in calcifying epithelioma: comparative studies with normal skin. Br J Dermatol 1994; 131: 506-513. (Pubitemid 24315418)
144. Fang S, Zeng FQ, Guo Q. Comparative proteomics analysis of cytokeratin and involucrin expression in lesions from patients with systemic lupus erythematosus. Acta Biochim Biophys Sin 2008; 40: 989-995.
145. Sui WG, Tang DE, Zou GM, Chen JJ, Ou ML, Zhang Y et al. Differential proteomic analysis of renal tissue in lupus nephritis using iTRAQ reagent technology. Rheumatol Int 2012; 32: 3537-3543.
146. Taher TE, Parikh K, Flores-Borja F, Mletzko S, Isenberg DA, Peppelenbosch MP et al. Protein phosphorylation and kinome profiling reveal altered regulation of multiple signaling pathways in B lymphocytes from patients with systemic lupus erythematosus. Arthritis & Rheumatism 2010; 62: 2412-2423.
147. Juang YT, Wang Y, Jiang G, Peng HB, Ergin S, Finnell M et al. PP2A dephosphorylates Elf-1 and determines the expression of CD3z and FcRg in human systemic lupus erythematosus T cells. J Immunol 2008; 181: 3658-3664.
148. Juang YT, Solomou E, Rellahan B, Tsokos GC. Phosphorylation and O-linked glycosylation of Elf-1 leads to its translocation to the nucleus and binding to the promoter of the T cell receptor z chain. J Immunol 2002; 168: 2865-2871. (Pubitemid 34211666)
149. Rellahan BL, Jensen JP, Weissman AM. Transcriptional regulation of the T cell antigen receptor zeta subunit: identification of a tissue-restricted promoter. J Exp Med 1994; 180: 1529-1534. (Pubitemid 24289626)
150. Honda S, Kobayashi T, Kajino K, Urakami S, Igawa M, Hino O. Ets protein Elf-1 bidirectionally suppresses transcriptional activities of the tumor suppressor Tsc2 gene and the repair-related Nth1 gene. Mol Carcinog 2003; 37: 122-129. (Pubitemid 36951357)
151. Doyle HA, Mamula MJ. Post-translational protein modifications in antigen recognition and autoimmunity. Trends Immunol 2001; 22: 443-449. (Pubitemid 32709979)
152. Utz PJ, Hottelet M, Schur PH, Anderson P. Proteins phosphorylated during stressinduced apoptosis are common targets for autoantibody production in patients with systemic lupus erythematosus. J Exp Med 1997; 185: 843-854. (Pubitemid 27119868)
153. Doyle HA, Mamula MJ. Autoantigenesis: the evolution of protein modifications in autoimmune disease. Curr Opin Immunol 2012; 24: 112-118.
154. Golan TD, Elkon KB, Gharavi AE, Krueger JG. Enhanced membrane binding of autoantibodies to cultured keratinocytes of systemic lupus erythematosus patients after ultraviolet B/ultraviolet A irradiation. J Clin Invest 1992; 90: 1067-1076.
155. Zhang C, Ao A, Seth A, Schlossman SF. A mitochondrial membrane protein defined by a novel monoclonal antibody is preferentially detected in apoptotic cells. J Immunol 1996; 157: 3980-3987. (Pubitemid 126449308)
156. Mevorach D, Zhou J, Elkon K. Immunization of mice with apoptotic cells induces low levels of autoantibodies. Arthritis Rheum 1996; 39: 143s.
157. Casciola-Rosen LA, Anhalt GJ, Rosen A. DNA-dependent protein kinase is one of a subset of autoantigens specifically cleaved early during apoptosis. J Exp Med 1995; 182: 1625-1634.
158. Terzoglou AG, Routsias JG, Avrameas S, Moutsopoulos HM, Tzioufas AG. Preferential recognition of the phosphorylated major linear B-cell epitope of La/SSB 349-368aa by anti-La/SSB autoantibodies from patients with systemic autoimmune diseases. Clin Exp Immunol 2006; 144: 432-439. (Pubitemid 43799926)
159. Terzoglou AG, Routsias JG, Moutsopoulos HM, Tzioufas AG. Post-translational modifications of the major linear epitope 169-190aa of Ro60 kDa autoantigen alter the autoantibody binding. Clin Exp Immunol 2006; 146: 60-65. (Pubitemid 44393839)
160. Tzioufas AG, Wassmuth R, Dafni UG, Guialis A, Haga HJ, Isenberg DA et al. Clinical, immunological, and immunogenetic aspects of autoantibody production against Ro/SSA, La/SSB and their linear epitopes in primary Sjogren's syndrome (pSS): a European multicentre study. Ann Rheum Dis 2002; 61: 398-404. (Pubitemid 34496817)
161. Hashii N, Kawasaki N, Itoh S, Nakajima Y, Kawanishi T, Yamaguchi T. Alteration of N-glycosylation in the kidney in a mouse model of systemic lupus erythematosus: relative quantification of N-glycans using an isotope-tagging method. Immunology 2009; 126: 336-345.
162. Gelsthorpe M, Pulumati M, McCallum C, Dang-Vu K, Tsubota SI. The putative cell cycle gene, enhancer of rudimentary, encodes a highly conserved protein found in plants and animals. Gene 1997; 186: 189-195. (Pubitemid 27107684)
163. Ouyang X, Dai Y, Wen JL, Wang LX. 1H NMR-based metabolomic study of metabolic profiling for systemic lupus erythematosus. Lupus 2011; 20: 1411-1420.
164. Michel P, Eggert W, Albrecht-Nebe H, Grune T. Increased lipid peroxidation in children with autoimmune disease. Acta Paediat 1997; 86: 609-612. (Pubitemid 27330424)
165. Serban MG, Tanaseanu S. Lipid peroxidation in autoimmune systemic vasculitides. Effect of corticoid treatment on lipid peroxidation. Antioxidant protection with vitamin E. Rom J Intern Med 1994; 32: 137-142. (Pubitemid 24322041)
166. Komatsu N, Kodama K, Yamanouchi N, Okada S, Noda S, Nawata Y et al. Metabolic rate for glucose in systemic lupus erythematosus patients with psychiatric symptoms. Eur Neurol 1999; 42: 41-48. (Pubitemid 29317482)
167. Alexander JJ, Zwingmann C, Quigg R. MRL/lpr mice have alterations in brain metabolism as shown with [1H-13C] NMR spectroscopy. Neurochem Int 2005; 47: 143-151.
168. Weiner SM, Otte A, Schumacher M, Brink I, Juengling FD, Sobanksi T et al. Alterations of cerebral glucose metabolism indicate progress to severe morphological brain lesions in neuropsychiatric systemic lupus erythematosus. Lupus 2000; 9: 386-389. (Pubitemid 30389044)
169. Laptook AR, Peterson J, Michael Porter A. Effects of lactic acid infusions and pH on cerebral blood flow and metabolism. J Cereb Blood Flow Metabol 1988; 8: 193-200. (Pubitemid 18079688)
170. Romick-Rosendale LE, Brunner HI, Bennett MR, Mina R, Nelson S, Petri M et al. Identification of urinary metabolites that distinguish membranous lupus nephritis from proliferative lupus nephritis and focal segmental glomerulosclerosis. Arthritis Res Ther 2011; 13: R199.
171. Christians U, Schmitz V, Schoning W, Bendrick-Peart J, Klawitter J, Haschke M et al. Toxicodynamic therapeutic drug monitoring of immunosuppressants: promises, reality and challenges. Ther Drug Monit 2008; 30: 151-158. (Pubitemid 351521641)
172. Quaggin SE, Kreidberg JA. Development of the renal glomerulus: good neighbors and good fences. Development 2008; 135: 609-620. (Pubitemid 351405014)
173. Hahn TJ, Hahn BH. Osteoporosis in patients with rheumatic diseases: principles of diagnosis and therapy. Semin Arthritis Rheum 1976; 6: 165-188.
174. Dykman TR, Gluck OS, Murphy WA, Hahn TJ, Hahn BH. Evaluation of factors associated with glucocorticoid-induced osteopenia in patients with rheumatic diseases. Arthritis Rheum 1985; 28: 361-368. (Pubitemid 15075486)
175. Kalla AA, Fataar AF, Jessop SJ, Bewerunge L. Loss of trabecular bone mineral density in systemic lupus erythematosus. Arthritis Rheum 1993; 36: 1726-1734. (Pubitemid 23360013)
176. Sels F, Dequeker J, Verwilghen J, Mbuyi-Muamba JM. SLE and osteoporosis: dependence and/or independence on glucocorticoids. Lupus 1996; 5: 89-92. (Pubitemid 26132219)
177. Kalla AA, Meyers OL, Parkyn ND, Kotze TJ. Osteoporosis screening-radiogrammetry revisited. Br J Rheumatol 1989; 28: 511-517.
178. Dhillon VB, Davies MC, Hall ML, Round JM, Ell PJ, Jacobs HS et al. Assessment of the effect of oral corticosteroids on bone mineral density in systemic lupus erythematosus: a preliminary study with dual energy x ray absorptiometry. Ann Rheum Dis 1990; 49: 624-626. (Pubitemid 20225435)
179. Hansen M, Halberg P, Kollerup G, Pedersen-Zbinden B, Hslev-Petersen K, Hyldstrup L et al. Bone metabolism in patients with systemic lupus erythematosus: effect of disease activity and glucocorticoid treatment. Scand J Rheumatol 1998; 27: 197-206. (Pubitemid 28267112)
180. Teichmann J, Lange U, Stracke H, Federlin K, Bretzel RG. Bone metabolism and bone mineral density of systemic lupus erythematosus at the time of diagnosis. Rheumatol Int 1999; 18: 137-140.
181. Redlich K, Ziegler S, Kiener HP, Spitzauer S, Stohlawetz P, Bernecker P et al. Bone mineral density and biochemical parameters of bone metabolism in female patients with systemic lupus erythematosus. Ann Rheum Dis 2000; 59: 308-310. (Pubitemid 30305576)