NF-κB and rheumatoid arthritis: Will understanding genetic risk lead to a therapeutic reward?

Forum on Immunopathological Diseases and Therapeutics

Volumn 4, Issue 2, 2013, Pages 93-110

  Scheinman, Robert ^a  

^a UNIVERSITY OF COLORADO   (United States)

Author keywords

A20; Genomewide association study (GWAS); NF B; REL; Rheumatoid arthritis (RA); Single nucleotide polymorphism (SNP); TNFAIP3; TRAF; Ubiquitin

Indexed keywords

ADALIMUMAB; BIOLOGICAL PRODUCT; CD40 ANTIGEN; ETANERCEPT; HLA DRB1 ANTIGEN; I KAPPA B; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INFLIXIMAB; METHOTREXATE; OSTEOCLAST DIFFERENTIATION FACTOR; TUMOR NECROSIS FACTOR ALPHA; TUMOR NECROSIS FACTOR RECEPTOR ASSOCIATED DEATH DOMAIN PROTEIN; TUMOR NECROSIS FACTOR RECEPTOR ASSOCIATED FACTOR 6; UBIQUITIN PROTEIN LIGASE E3;

ANTIBODY PRODUCTION; B LYMPHOCYTE; CELL SURVIVAL; DIMERIZATION; ENZYME ACTIVITY; GENE FREQUENCY; GENE LOCUS; GENE REPRESSION; GENETIC ASSOCIATION; GENETIC RECOMBINATION; GENETIC RISK; GENETIC TRANSCRIPTION; GENETIC VARIABILITY; HUMAN; IMMUNOMODULATION; NONHUMAN; PRIORITY JOURNAL; PROMOTER REGION; PROTEIN ANALYSIS; PROTEIN DEGRADATION; PROTEIN DOMAIN; PROTEIN FUNCTION; PROTEIN PHOSPHORYLATION; PROTEIN PROCESSING; PROTEIN PROTEIN INTERACTION; REVIEW; RHEUMATOID ARTHRITIS; SIGNAL TRANSDUCTION; SINGLE NUCLEOTIDE POLYMORPHISM; T LYMPHOCYTE; TNFAIP3 GENE; UBIQUITINATION;

EID: 84892523749     PISSN: 21518017     EISSN: 21518025     Source Type: Journal    
DOI: 10.1615/ForumImmunDisTher.2013008408     Document Type: Review

References (106)

1. McInnes IB, Schett G. The pathogenesis of rheumatoid arthritis. N Engl J Med. 2011;365:2205-19.
2. van Venrooij WJ, van Beers JJ, Pruijn GJ. Anti-CCP antibodies: The past, the present and the future. Nat Rev Rheumatol. 2011;7:391-8.
3. Vallabhapurapu S, Karin M. Regulation and function of NF-kappaB transcription factors in the immune system. Annu Rev Immunol. 2009;27:693-733.
4. Kaltschmidt B, Kaltschmidt C. NF-kappaB in the nervous system. Cold Spring Harb Perspect Biol. 2009;1:a001271.
5. Tornatore L, Thotakura AK, Bennett J, Moretti M, Franzoso G. The nuclear factor kappa B signaling pathway: Integrating metabolism with inflammation. Trends Cell Biol. 2012;22:557-66.
6. Abecasis GR, Altshuler D, Auton A, Brooks LD, Durbin RM, Gibbs RA, Hurles ME, McVean GA. A map of human genome variation from population-scale sequencing. Nature. 2010;467:1061-73.
7. Bush WS, Moore JH. Chapter 11: Genomewide association studies. PLoS Comput Biol. 2012;8:e1002822.
8. Brown KD, Claudio E, Siebenlist U. The roles of the classical and alternative nuclear factor-kappaB pathways: Potential implications for autoimmunity and rheumatoid arthritis. Arthritis Res Ther. 2008;10:212.
9. Hayden MS, Ghosh S. Signaling to NF-kappaB. Genes Dev. 2004;18:2195-224.
10. Li Q, Verma IM. NF-kappaB regulation in the immune system. Nat Rev Immunol. 2002;2:725-34.
11. Razani B, Reichardt AD, Cheng G. Non-canonical NF-kappaB signaling activation and regulation: Principles and perspectives. Immunol Rev. 2011;244:44-54.
12. Sun SC. The noncanonical NF-kappaB pathway. Immunol Rev. 2012;246:125-40.
13. Liu F, Xia Y, Parker AS, Verma IM. IKK biology. Immunol Rev. 2012;246:239-53.
14. Smale ST. Dimer-specific regulatory mechanisms within the NF-kappaB family of transcription factors. Immunol Rev. 2012;246:193-204.
15. Natoli G. NF-kappaB and chromatin: Ten years on the path from basic mechanisms to candidate drugs. Immunol Rev. 2012;246:183-92.
16. Smale ST. Hierarchies of NF-kappaB target-gene regulation. Nat Immunol. 2011;12:689-94.
17. Bhoj VG, Chen ZJ. Ubiquitylation in innate and adaptive immunity. Nature. 2009;458:430-7.
18. Ikeda F, Dikic I. Atypical ubiquitin chains: New molecular signals. EMBO Rep. 2008;9:536-42.
19. Emmerich CH, Schmukle AC, Walczak H. The emerging role of linear ubiquitination in cell signaling. Sci Signal. 2011;4:re5.
20. Chen ZJ, Sun LJ. Nonproteolytic functions of ubiquitin in cell signaling. Mol Cell. 2009;33:275-86.
21. Gregersen PK, Silver J, Winchester RJ. The shared epitope hypothesis: An approach to understanding the molecular genetics of susceptibility to rheumatoid arthritis. Arthritis Rheum. 1987;30:1205-13.
22. Ding B, Padyukov L, Lundstrom E, Seielstad M, Plenge RM, Oksenberg JR, Gregersen PK, Alfredsson L, Klareskog L. Different patterns of associations with anti-citrullinated protein antibody-positive and anti-citrullinated protein antibody-negative rheumatoid arthritis in the extended major histocompatibility complex region. Arthritis Rheum. 2009;60:30-8.
23. Lee HS, Lee AT, Criswell LA, Seldin MF, Amos CI, Carulli JP, Navarrete C, Remmers EF, Kastner DL, Plenge RM, Li W, Gregersen PK. Several regions in the major histocompatibility complex confer risk for anti-CCP-antibody positive rheumatoid arthritis, independent of the DRB1 locus. Mol Med. 2008;14:293-300.
24. Vignal C, Bansal AT, Balding DJ, Binks MH, Dickson MC, Montgomery DS, Wilson AG. Genetic association of the major histocompatibility complex with rheumatoid arthritis implicates two non-DRB1 loci. Arthritis Rheum. 2009;60:53-62.
25. Gregersen PK, Batliwalla F. PTPN22 and rheumatoid arthritis: gratifying replication. Arthritis Rheum. 2005;52:1952-5.
26. Gregersen PK, Lee HS, Batliwalla F, Begovich AB. PTPN22: Setting thresholds for autoimmunity. Semin Immunol. 2006;18:214-23.
27. Wellcome-Trust-Consortium. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature. 2007;447:661-78.
28. Thomson W, Barton A, Ke X, Eyre S, Hinks A, Bowes J, Donn R, Symmons D, Hider S, Bruce IN; Wellcome Trust Case Control Consortium, Wilson AG, Marinou I, Morgan A, Emery P; YEAR Consortium, Carter A, Steer S, Hocking L, Reid DM, Wordsworth P, Harrison P, Strachan D, Worthington J. Rheumatoid arthritis association at 6q23. Nat Genet. 2007;39:1431-3.
29. Plenge RM, Cotsapas C, Davies L, Price AL, de Bakker PI, Maller J, Pe'er I, Burtt NP, Blumenstiel B, DeFelice M, Parkin M, Barry R, Winslow W, Healy C, Graham RR, Neale BM, Izmailova E, Roubenoff R, Parker AN, Glass R, Karlson EW, Maher N, Hafler DA, Lee DM, Seldin MF, Remmers EF, Lee AT, Padyukov L, Alfredsson L, Coblyn J, Weinblatt ME, Gabriel SB, Purcell S, Klareskog L, Gregersen PK, Shadick NA, Daly MJ, Altshuler D. Two independent alleles at 6q23 associated with risk of rheumatoid arthritis. Nat Genet. 2007;39:1477-82.
30. Sun F, Li P, Chen H, Wu Z, Xu J, Shen M, Leng X, Shi Q, Zhang W, Tian X, Li Y, Zhang F. Association studies of TNFSF4, TNFAIP3 and FAM167A-BLK polymorphisms with primary Sjogren's syndrome in Han Chinese. J Hum Genet. 2013;58(7):475-9.
31. Graham RR, Cotsapas C, Davies L, Hackett R, Lessard CJ, Leon JM, Burtt NP, Guiducci C, Parkin M, Gates C, Plenge RM, Behrens TW, Wither JE, Rioux JD, Fortin PR, Graham DC, Wong AK, Vyse TJ, Daly MJ, Altshuler D, Moser KL, Gaffney PM. Genetic variants near TNFAIP3 on 6q23 are associated with systemic lupus erythematosus. Nat Genet. 2008;40:1059-61.
32. Fung EY, Smyth DJ, Howson JM, Cooper JD, Walker NM, Stevens H, Wicker LS, Todd JA. Analysis of 17 autoimmune disease-associated variants in type 1 diabetes identifies 6q23/ TNFAIP3 as a susceptibility locus. Genes Immun. 2009;10:188-91.
33. Ben Hamad M, Cornelis F, Maalej A, Petit-Teixeira E. A Tunisian case-control association study of a 6q polymorphism in rheumatoid arthritis. Rheumatol Int. 2012;32:1849-50.
34. Dieguez-Gonzalez R, Calaza M, Perez-Pampin E, Balsa A, Blanco FJ, Cañete JD, Caliz R, Carreño L, de la Serna AR, Fernandez-Gutierrez B, Ortiz AM, Herrero-Beaumont G, Pablos JL, Narvaez J, Navarro F, Marenco JL, Gomez-Reino JJ, Gonzalez A. Analysis of TNFAIP3, a feedback inhibitor of nuclear factor-kappaB and the neighbor intergenic 6q23 region in rheumatoid arthritis susceptibility. Arthritis Res Ther. 2009;11:R42.
35. Kawasaki A, Ito I, Ito S, Hayashi T, Goto D, Matsumoto I, Takasaki Y, Hashimoto H, Sumida T, Tsuchiya N. Association of TNFAIP3 polymorphism with susceptibility to systemic lupus erythematosus in a Japanese population. J Biomed Biotechnol. 2010;2010:207578.
36. Opipari AW Jr., HM Hu, Yabkowitz R, Dixit VM. The A20 zinc finger protein protects cells from tumor necrosis factor cytotoxicity. J Biol Chem. 1992;267:12424-7.
37. Lee EG, Boone DL, Chai S, Libby SL, Chien M, Lodolce JP, Ma A.Failure to regulate TNF-induced NF-kappaB and cell death responses in A20-deficient mice. Science. 2000;289:2350-4.
38. Matmati M, Jacques P, Maelfait J, Verheugen E, Kool M, Sze M, Geboes L, Louagie E, Mc Guire C, Vereecke L, Chu Y, Boon L, Staelens S, Matthys P, Lambrecht BN, Schmidt-Supprian M, Pasparakis M, Elewaut D, Beyaert R, van Loo G. A20 (TNFAIP3) deficiency in myeloid cells triggers erosive polyarthritis resembling rheumatoid arthritis. Nat Genet. 2011;43:908-12.
39. Adrianto I, Wen F, Templeton A, Wiley G, King JB, Lessard CJ, Bates JS, Hu Y, Kelly JA, Kaufman KM, Guthridge JM, Alarcón-Riquelme ME; BIOLUPUS and GENLES Networks, Anaya JM, Bae SC, Bang SY, Boackle SA, Brown EE, Petri MA, Gallant C, Ramsey-Goldman R, Reveille JD, Vila LM, Criswell LA, Edberg JC, Freedman BI, Gregersen PK, Gilkeson GS, Jacob CO, James JA, Kamen DL, Kimberly RP, Martin J, Merrill JT, Niewold TB, Park SY, Pons-Estel BA, Scofield RH, Stevens AM, Tsao BP, Vyse TJ, Langefeld CD, Harley JB, Moser KL, Webb CF, Humphrey MB, Montgomery CG, Gaffney PM. Association of a functional variant downstream of TNFAIP3 with systemic lupus erythematosus. Nat Genet. 2011;43:253-8.
40. Boyle AP, Hong EL, Hariharan M, Cheng Y, Schaub MA, Kasowski M, Karczewski KJ, Park J, Hitz BC, Weng S, Cherry JM, Snyder M. Annotation of functional variation in personal genomes using RegulomeDB. Genome Res. 2012;22:1790-7.
41. Musone SL, Taylor KE, Nititham J, Chu C, Poon A, Liao W, Lam ET, Ma A, Kwok PY, Criswell LA. Sequencing of TNFAIP3 and association of variants with multiple autoimmune diseases. Genes Immun. 2011;12:176-82.
42. Song HY, Rothe M, Goeddel DV. The tumor necrosis factor-inducible zinc finger protein A20 interacts with TRAF1/TRAF2 and inhibits NF-kappaB activation. Proc Natl Acad Sci USA. 1996;93:6721-5.
43. Heyninck K, Beyaert R. The cytokine-inducible zinc finger protein A20 inhibits IL-1-induced NF-kappaB activation at the level of TRAF6. FEBS Lett. 1999;442:147-50.
44. Evans PC, Ovaa H, Hamon M, Kilshaw PJ, Hamm S, Bauer S, Ploegh HL, Smith TS. Zinc-finger protein A20, a regulator of inflammation and cell survival, has de-ubiquitinating activity. Biochem J. 2004;378:727-34.
45. Wertz IE, O'Rourke KM, Zhou H, Eby M, Aravind L, Seshagiri S, Wu P, Wiesmann C, Baker R, Boone DL, Ma A, Koonin EV, Dixit VM. De-ubiquitination and ubiquitin ligase domains of A20 downregulate NF-kappaB signalling. Nature. 2004;430:694-9.
46. Lu TT, Onizawa M, Hammer GE, Turer EE, Yin Q, Damko E, Agelidis A, Shifrin N, Advincula R, Barrera J, Malynn BA, Wu H, Ma A. Dimerization and ubiquitin mediated recruitment of a20, a complex deubiquitinating enzyme. Immunity. 2013;38:896-905.
47. Skaug B, Chen J, Du F, He J, Ma A, Chen ZJ. Direct, noncatalytic mechanism of IKK inhibition by A20. Mol Cell. 2011;44:559-71.
48. Tokunaga F, Nishimasu H, Ishitani R, Goto E, Noguchi T, Mio K, Kamei K, Ma A, Iwai K, Nureki O. Specific recognition of linear polyubiquitin by A20 zinc finger 7 is involved in NF-kappaB regulation. Embo J. 2012;31:3856-70.
49. Verhelst K, Carpentier I, Kreike M, Meloni L, Verstrepen L, Kensche T, Dikic I, Beyaert R. A20 inhibits LUBAC-mediated NF-kappaB activation by binding linear polyubiquitin chains via its zinc finger 7. Embo J. 2012;31:3845-55.
50. Plenge RM, Seielstad M, Padyukov L, Lee AT, Remmers EF, Ding B, Liew A, Khalili H, Chandrasekaran A, Davies LR, Li W, Tan AK, Bonnard C, Ong RT, Thalamuthu A, Pettersson S, Liu C, Tian C, Chen WV, Carulli JP, Beckman EM, Altshuler D, Alfredsson L, Criswell LA, Amos CI, Seldin MF, Kastner DL, Klareskog L, Gregersen PK. TRAF1-C5 as a risk locus for rheumatoid arthritis-A genomewide study. N Engl J Med. 2007;357:1199-209.
51. Chang M, Rowland CM, Garcia VE, Schrodi SJ, Catanese JJ, van der Helm-van Mil AH, Ardlie KG, Amos CI, Criswell LA, Kastner DL, Gregersen PK, Kurreeman FA, Toes RE, Huizinga TW, Seldin MF, Begovich AB. A large-scale rheumatoid arthritis genetic study identifies association at chromosome 9q33.2. PLoS Genet. 2008;4:e1000107.
52. Fakhfakh Karray E, Chalbi H, Ben Dhifallah I, Zakraoui L, Hamzaoui K. Association study of TRAF1-C5 polymorphism with susceptibility to rheumatoid arthritis in Tunisian population. Joint Bone Spine. 2012;79:331-2.
53. Han TU, Bang SY, Kang C, Bae SC. TRAF1 polymorphisms associated with rheumatoid arthritis susceptibility in Asians and in Caucasians. Arthritis Rheum. 2009;60:2577-84.
54. Mohamed RH, Pasha HF, El-Shahawy EE. Influence of TRAF1/C5 and STAT4 genes polymorphisms on susceptibility and severity of rheumatoid arthritis in Egyptian population. Cell Immunol. 2012;273:67-72.
55. Zhu J, Zhang D, Wu F, He F, Liu X, Wu L, Zhou B, Liu J, Lu F, Liu J, Luo R, Long W, Yang M, Ma S, Wu X, Shi Y, Wu T, Lin Y, Yang J, Yuan G, Yang Z. Single nucleotide polymorphisms at the TRAF1/C5 locus are associated with rheumatoid arthritis in a Han Chinese population. BMC Med Genet. 2011;12:53.
56. Plant D, Thomson W, Lunt M, Flynn E, Martin P, Eyre S, Farragher T, Bunn D, Worthington J, Symmons D, Barton A. The role of rheumatoid arthritis genetic susceptibility markers in the prediction of erosive disease in patients with early inflammatory polyarthritis: Results from the Norfolk Arthritis Register. Rheumatology (Oxford). 2011;50:78-84.
57. Viatte S, Plant D, Lunt M, Fu B, Flynn E, Parker BJ, Galloway J, Solymossy C, Worthington J, Symmons DP, Dixey JJ, Young A, Barton A. Investigation of rheumatoid arthritis genetic susceptibility markers in the early rheumatoid arthritis study further replicates the TRAF1 association with radiological damage. J Rheumatol. 2013;40:144-56.
58. Palomino-Morales R, Gonzalez-Juanatey C, Vazquez-Rodriguez TR, Rodriguez L, Miranda-Filloy JA, Pascual-Salcedo D, Balsa A, Fernandez-Gutierrez B, Llorca J, Martin J, Gonzalez-Gay MA. Lack of association of PTPN22, STAT4 and TRAF1/C5 gene polymorphisms with cardiovascular risk in rheumatoid arthritis. Clin Exp Rheumatol. 2010;28:695-701.
59. Rothe M, Wong SC, Henzel WJ, Goeddel DV. A novel family of putative signal transducers associated with the cytoplasmic domain of the 75 kDa tumor necrosis factor receptor. Cell. 1994;78:681-92.
60. Bradley JR, Pober JS. Tumor necrosis factor receptor-associated factors (TRAFs). Oncogene. 2001;20:6482-91.
61. Carpentier I, Beyaert R. TRAF1 is a TNF inducible regulator of NF-kappaB activation. FEBS Lett. 1999;460:246-50.
62. Schwenzer R, Siemienski K, Liptay S, Schubert G, Peters N, Scheurich P, Schmid RM, Wajant H. The human tumor necrosis factor (TNF) receptor-associated factor 1 gene (TRAF1) is up-regulated by cytokines of the TNF ligand family and modulates TNF-induced activation of NF-kappaB and c-Jun N-terminal kinase. J Biol Chem. 1999;274:19368-74.
63. Tsitsikov EN, Laouini D, Dunn IF, Sannikova TY, Davidson L, Alt FW, Geha RS. TRAF1 is a negative regulator of TNF signaling. enhanced TNF signaling in TRAF1-deficient mice. Immunity. 2001;15:647-57.
64. Xie P, Hostager BS, Munroe ME, Moore CR, Bishop GA. Cooperation between TNF receptor-associated factors 1 and 2 in CD40 signaling. J Immunol. 2006;176:5388-400.
65. Arron JR, Pewzner-Jung Y, Walsh MC, Kobayashi T, Choi Y. Regulation of the subcellular localization of tumor necrosis factor receptor-associated factor (TRAF)2 by TRAF1 reveals mechanisms of TRAF2 signaling. J Exp Med. 2002;196:923-34.
66. Sughra K, Birbach A, de Martin R, Schmid JA. Interaction of the TNFR-receptor associated factor TRAF1 with I-kappa B kinase-2 and TRAF2 indicates a regulatory function for NF-kappa B signaling. PLoS One. 2010;5:e12683.
67. McPherson AJ, Snell LM, Mak TW, Watts TH. Opposing roles for TRAF1 in the alternative versus classical NF-kappaB pathway in T cells. J Biol Chem. 2012;287:23010-9.
68. Choudhary S, Kalita M, Fang L, Patel KV, Tian B, Zhao Y, Edeh CB, Brasier AR. Inducible tumor necrosis factor (TNF) receptor-associated factor-1 expression couples the canonical to the non-canonical NF-kappaB pathway in TNF stimulation. J Biol Chem. 2013;288:14612-23.
69. Potter C, Eyre S, Cope A, Worthington J, Barton A. Investigation of association between the TRAF family genes and RA susceptibility. Ann Rheum Dis. 2007;66:1322-6.
70. Raychaudhuri S, Plenge RM, Rossin EJ, Ng AC; International Schizophrenia Consortium, Purcell SM, Sklar P, Scolnick EM, Xavier RJ, Altshuler D, Daly MJ. Identifying relationships among genomic disease regions: Predicting genes at pathogenic SNP associations and rare deletions. PLoS Genet. 2009;5:e1000534.
71. Raychaudhuri S, Thomson BP, Remmers EF, Eyre S, Hinks A, Guiducci C, Catanese JJ, Xie G, Stahl EA, Chen R, Alfredsson L, Amos CI, Ardlie KG; BIRAC Consortium, Barton A, Bowes J, Burtt NP, Chang M, Coblyn J, Costenbader KH, Criswell LA, Crusius JB, Cui J, De Jager PL, Ding B, Emery P, Flynn E, Harrison P, Hocking LJ, Huizinga TW, Kastner DL, Ke X, Kurreeman FA, Lee AT, Liu X, Li Y, Martin P, Morgan AW, Padyukov L, Reid DM, Seielstad M, Seldin MF, Shadick NA, Steer S, Tak PP, Thomson W, van der Helm-van Mil AH, van der Horst-Bruinsma IE, Weinblatt ME, Wilson AG, Wolbink GJ, Wordsworth P; YEAR Consortium, Altshuler D, Karlson EW, Toes RE, de Vries N, Begovich AB, Siminovitch KA, Worthington J, Klareskog L, Gregersen PK, Daly MJ, Plenge RM. Genetic variants at CD28, PRDM1 and CD2/CD58 are associated with rheumatoid arthritis risk. Nat Genet. 2009;41:1313-8.
72. Lomaga MA, Yeh WC, Sarosi I, Duncan GS, Furlonger C, Ho A, Morony S, Capparelli C, Van G, Kaufman S, van der Heiden A, Itie A, Wakeham A, Khoo W, Sasaki T, Cao Z, Penninger JM, Paige CJ, Lacey DL, Dunstan CR, Boyle WJ, Goeddel DV, Mak TW. TRAF6 deficiency results in osteopetrosis and defective interleukin-1, CD40, and LPS signaling. Genes Dev. 1999;13:1015-24.
73. Duran A, Serrano M, Leitges M, Flores JM, Picard S, Brown JP, Moscat J, Diaz-Meco MT. The atypical PKC-interacting protein p62 is an important mediator of RANK-activated osteoclastogenesis. Dev Cell. 2004;6:303-9.
74. Takeda K, Akira S. TLR signaling pathways. Semin Immunol. 2004;16:3-9.
75. Goh FG, Midwood KS. Intrinsic danger: Activation of Toll-like receptors in rheumatoid arthritis. Rheumatology (Oxford). 2012;51:7-23.
76. Coenen MJ, Enevold C, Barrera P, Schijvenaars MM, Toonen EJ, Scheffer H, Padyukov L, Kastbom A, Klareskog L, Barton A, Kievit W, Rood MJ, Jansen TL, Swinkels D, van Riel PL, Franke B, Bendtzen K, Radstake TR. Genetic variants in toll-like receptors are not associated with rheumatoid arthritis susceptibility or anti-tumour necrosis factor treatment outcome. PLoS One. 2010;5:e14326.
77. Lee YH. Bae SC. Song GG. Meta-analysis demonstrates association between TLR polymorphisms and rheumatoid arthritis. Genet Mol Res. 12(1):328-34.
78. Raychaudhuri S, Remmers EF, Lee AT, Hackett R, Guiducci C, Burtt NP, Gianniny L, Korman BD, Padyukov L, Kurreeman FA, Chang M, Catanese JJ, Ding B, Wong S, van der Helm-van Mil AH, Neale BM, Coblyn J, Cui J, Tak PP, Wolbink GJ, Crusius JB, van der Horst-Bruinsma IE, Criswell LA, Amos CI, Seldin MF, Kastner DL, Ardlie KG, Alfredsson L, Costenbader KH, Altshuler D, Huizinga TW, Shadick NA, Weinblatt ME, de Vries N, Worthington J, Seielstad M, Toes RE, Karlson EW, Begovich AB, Klareskog L, Gregersen PK, Daly MJ, Plenge RM. Common variants at CD40 and other loci confer risk of rheumatoid arthritis. Nat Genet. 2008;40:1216-23.
79. Lee HS, Korman BD, Le JM, Kastner DL, Remmers EF, Gregersen PK, Bae SC. Genetic risk factors for rheumatoid arthritis differ in Caucasian and Korean populations. Arthritis Rheum. 2009;60:364-71.
80. Orozco G, Eyre S, Hinks A, Ke X, Wellcome Trust Case Control consortium YEAR Consortium, Wilson AG, Bax DE, Morgan AW, Emery P, Steer S, Hocking L, Reid DM, Wordsworth P, Harrison P, Thomson W, Barton A, Worthington J. Association of CD40 with rheumatoid arthritis confirmed in a large UK case-control study. Ann Rheum Dis. 2010;69:813-6.
81. Prasad P, Kumar A, Gupta R, Juyal RC, Thelma BK. Caucasian and Asian specific rheumatoid arthritis risk loci reveal limited replication and apparent allelic heterogeneity in north Indians. PLoS One. 2012;7:e31584.
82. van der Linden MP, Feitsma AL, le Cessie S, Kern M, Olsson LM, Raychaudhuri S, Begovich AB, Chang M, Catanese JJ, Kurreeman FA, van Nies J, van der Heijde DM, Gregersen PK, Huizinga TW, Toes RE, van der Helm-Van Mil AH. Association of a single-nucleotide polymorphism in CD40 with the rate of joint destruction in rheumatoid arthritis. Arthritis Rheum. 2009;60:2242-7.
83. Li G, Diogo D, Wu D, Spoonamore J, Dancik V, Franke L, Kurreeman F, Rossin EJ, Duclos G, Hartland C, Zhou X, Li K, Liu J, De Jager PL, Siminovitch KA, Zhernakova A, Raychaudhuri S, Bowes J, Eyre S, Padyukov L, Gregersen PK, Worthington J; Rheumatoid Arthritis Consortium International (RACI), Gupta N, Clemons PA, Stahl E, Tolliday N, Plenge RM. Human genetics in rheumatoid arthritis guides a high-throughput drug screen of the CD40 signaling pathway. PLoS Genet. 2013;9:e1003487.
84. Peters AL, Stunz LL, Bishop, GA. CD40 and autoimmunity: The dark side of a great activator. Semin Immunol. 2009;21:293-300.
85. Munroe ME, Bishop GA. A costimulatory function for T cell CD40. J Immunol. 2007;178:671-82.
86. Berner B, Wolf G, Hummel KM, Muller GA, Reuss-Borst MA. Increased expression of CD40 ligand (CD154) on CD4+ T cells as a marker of disease activity in rheumatoid arthritis. Ann Rheum Dis. 2000;59:190-5.
87. Zhang X, Burch E, Cai L, So E, Hubbard F, Matteson EL, Strome SE. CD40 mediates down-regulation of CD32B on specific memory B Cell populations in rheumatoid arthritis. J Immunol. 2013;190:6015-22.
88. Durie FH, Fava RA, Foy TM, Aruffo A, Ledbetter JA, Noelle RJ. Prevention of collagen-induced arthritis with an antibody to gp39, the ligand for CD40. Science. 1993;261:1328-30.
89. Kyburz D, Carson DA, Corr M. The role of CD40 ligand and tumor necrosis factor alpha signaling in the transgenic K/BxN mouse model of rheumatoid arthritis. Arthritis Rheum. 2000;43:2571-7.
90. Mauri C, Mars LT, Londei M. Therapeutic activity of agonistic monoclonal antibodies against CD40 in a chronic autoimmune inflammatory process. Nat Med. 2000;6:673-9.
91. Gregersen PK, Amos CI, Lee AT, Lu Y, Remmers EF, Kastner DL, Seldin MF, Criswell LA, Plenge RM, Holers VM, Mikuls TR, Sokka T, Moreland LW, Bridges SL Jr, Xie G, Begovich AB, Siminovitch KA. REL, encoding a member of the NF-kappaB family of transcription factors, is a newly defined risk locus for rheumatoid arthritis. Nat Genet. 2009;41:820-3.
92. Eyre S, Hinks A, Flynn E, Martin P, Wilson AG, Maxwell JR, Morgan AW, Emery P, Steer S, Hocking LJ, Reid DM, Harrison P, Wordsworth P, Thomson W, Worthington J, Barton A. Confirmation of association of the REL locus with rheumatoid arthritis susceptibility in the UK population. Ann Rheum Dis. 2010;69:1572-3.
93. Sen R, Smale ST. Selectivity of the NF-{kappa} B response. Cold Spring Harb Perspect Biol. 2009;2:a000257.
94. Zhou XY, Yashiro-Ohtani Y, Nakahira M, Park WR, Abe R, Hamaoka T, Naramura M, Gu H, Fujiwara H. Molecular mechanisms underlying differential contribution of CD28 versus non-CD28 costimulatory molecules to IL-2 promoter activation. J Immunol. 2002;168:3847-54.
95. Ouaaz F, Arron J, Zheng Y, Choi Y, Beg AA. Dendritic cell development and survival require distinct NF-kappaB subunits. Immunity. 2002;16:257-70.
96. Lio CW, Hsieh CS. Becoming self-aware: The thymic education of regulatory T cells. Curr Opin Immunol. 2011;23:213-9.
97. Chang M, Jin W, Chang JH, Xiao Y, Brittain GC, Yu J, Zhou X, Wang YH, Cheng X, Li P, Rabinovich BA, Hwu P, Sun SC. The ubiquitin ligase Peli1 negatively regulates T cell activation and prevents autoimmunity. Nat Immunol. 2011;12:1002-9.
98. Breedveld FC, Weisman MH, Kavanaugh AF, Cohen SB, Pavelka K, van Vollenhoven R, Sharp J, Perez JL, Spencer-Green GT. The PREMIER study: A multicenter, randomized, double-blind clinical trial of combination therapy with adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in patients with early, aggressive rheumatoid arthritis who had not had previous methotrexate treatment. Arthritis Rheum. 2006;54:26-37.
99. van den Broek M, Visser K, Allaart CF, Huizinga TW. Personalized medicine: Predicting responses to therapy in patients with RA. Curr Opin Pharmacol. 2013;13:463-9.
100. Canhao H, Rodrigues AM, Mourao AF, Martins F, Santos MJ, Canas-Silva J, Polido-Pereira J, Pereira Silva JA, Costa JA, Araújo D, Silva C, Santos H, Duarte C, da Silva JA, Pimentel-Santos FM, Branco JC, Karlson EW, Fonseca JE, Solomon DH. Comparative effectiveness and predictors of response to tumour necrosis factor inhibitor therapies in rheumatoid arthritis. Rheumatology (Oxford). 2012;51:2020-6.
101. Kleinert S, Tony HP, Krause A, Feuchtenberger M, Wassenberg S, Richter C, Röther E, Spieler W, Gnann H, Wittig BM. Impact of patient and disease characteristics on therapeutic success during adalimumab treatment of patients with rheumatoid arthritis: Data from a German non-interventional observational study. Rheumatol Int. 2012;32:2759-67.
102. Klaasen R, Cantaert T, Wijbrandts CA, Teitsma C, Gerlag DM, Out TA, de Nooijer MJ, Baeten D, Tak PP. The value of rheumatoid factor and anti-citrullinated protein antibodies as predictors of response to infliximab in rheumatoid arthritis: An exploratory study. Rheumatology (Oxford). 2011;50:1487-93.
103. Cui J, Stahl EA, Saevarsdottir S, Miceli C, Diogo D, Trynka G, Raj T, Mirkov MU, Canhao H, Ikari K, Terao C, Okada Y, Wedrén S, Askling J, Yamanaka H, Momohara S, Taniguchi A, Ohmura K, Matsuda F, Mimori T, Gupta N, Kuchroo M, Morgan AW, Isaacs JD, Wilson AG, Hyrich KL, Herenius M, Doorenspleet ME, Tak PP, Crusius JB, van der Horst-Bruinsma IE, Wolbink GJ, van Riel PL, van de Laar M, Guchelaar HJ, Shadick NA, Allaart CF, Huizinga TW, Toes RE, Kimberly RP, Bridges SL Jr, Criswell LA, Moreland LW, Fonseca JE, de Vries N, Stranger BE, De Jager PL, Raychaudhuri S, Weinblatt ME, Gregersen PK, Mariette X, Barton A, Padyukov L, Coenen MJ, Karlson EW, Plenge RM. Genome-wide association study and gene expression analysis identifies CD84 as a predictor of response to etanercept therapy in rheumatoid arthritis. PLoS Genet. 2013;9:e1003394.
104. Cannons JL, Tangye SG, Schwartzberg PL. SLAM family receptors and SAP adaptors in immunity. Annu Rev Immunol. 2011;29:665-705.
105. Coulthard LR, Taylor JC, Eyre S, Biologics in Rheumatoid Arthritis Genetics and Genomics, Robinson JI, Wilson AG, Isaacs JD, Hyrich K, Emery P, Barton A, Barrett JH, Morgan AW, McDermott MF. Genetic variants within the MAP kinase signalling network and anti-TNF treatment response in rheumatoid arthritis patients. Ann Rheum Dis. 2012;70:98-103.
106. Zeng Z, Duan Z, Zhang T, Wang S, Li G, Gao J, Ye D, Xu S, Xu J, Zhang L, Pan F. Association between tumor necrosis factor-alpha (TNF-alpha) promoter -308 G/A and response to TNF-alpha blockers in rheumatoid arthritis: A meta-analysis. Mod Rheumatol. 2013;23:489-95.