646
Views
1
CrossRef citations to date
0
Altmetric
Review

The potential of PTPN22 as a therapeutic target for rheumatoid arthritis

&
Pages 879-891 | Received 02 Apr 2018, Accepted 18 Sep 2018, Published online: 07 Oct 2018

References

  • McInnes IB, Schett G. The pathogenesis of rheumatoid arthritis. N Engl J Med. 2011;365(23):2205–2219. PubMed PMID: 22150039.
  • Chung WS, Peng CL, Lin CL, et al. Rheumatoid arthritis increases the risk of deep vein thrombosis and pulmonary thromboembolism: a nationwide cohort study. Ann Rheum Dis. 2014;73(10):1774–1780. PubMed PMID: 23926057.
  • Yu KH, See LC, Kuo CF, et al. Prevalence and incidence in patients with autoimmune rheumatic diseases: a nationwide population-based study in Taiwan. Arthritis Care Res. 2013;65(2):244–250. PubMed PMID: 22899470.
  • Neovius M, Simard JF, Askling J. Nationwide prevalence of rheumatoid arthritis and penetration of disease-modifying drugs in Sweden. Ann Rheum Dis. 2011;70(4):624–629. PubMed PMID: 21149495.
  • Cross M, Smith E, Hoy D, et al. The global burden of rheumatoid arthritis: estimates from the global burden of disease 2010 study. Ann Rheum Dis. 2014;73(7):1316–1322. PubMed PMID: 24550173.
  • Smolen JS, Aletaha D, McInnes IB. Rheumatoid arthritis. Lancet. 2016;388(10055):2023–2038. PubMed PMID: 27156434.
  • Viatte S, Plant D, Raychaudhuri S. Genetics and epigenetics of rheumatoid arthritis. Nat Rev Rheumatol. 2013;9(3):141–153. PubMed PMID: 23381558; PubMed Central PMCID: PMC3694322.
  • Jiang X, Frisell T, Askling J, et al. To what extent is the familial risk of rheumatoid arthritis explained by established rheumatoid arthritis risk factors? Arthritis Rheumatol. 2015;67(2):352–362. PubMed PMID: 25418518.
  • Frisell T, Hellgren K, Alfredsson L, et al. Familial aggregation of arthritis-related diseases in seropositive and seronegative rheumatoid arthritis: a register-based case-control study in Sweden. Ann Rheum Dis. 2016;75(1):183–189. PubMed PMID: 25498119; PubMed Central PMCID: PMC4465879.
  • MacGregor AJ, Snieder H, Rigby AS, et al. Characterizing the quantitative genetic contribution to rheumatoid arthritis using data from twins. Arthritis Rheum. 2000;43(1):30–37. PubMed PMID: 10643697.
  • Okada Y, Wu D, Trynka G, et al. Genetics of rheumatoid arthritis contributes to biology and drug discovery. Nature. 2014;506(7488):376–381. PubMed PMID: 24390342; PubMed Central PMCID: PMC3944098.
  • Parkes M, Cortes A, van Heel DA, et al. Genetic insights into common pathways and complex relationships among immune-mediated diseases. Nat Rev Genet. 2013;14(9):661–673. PubMed PMID: 23917628.
  • Raychaudhuri S, Sandor C, Stahl EA, et al. Five amino acids in three HLA proteins explain most of the association between MHC and seropositive rheumatoid arthritis. Nat Genet. 2012;44(3):291–296. PubMed PMID: 22286218; PubMed Central PMCID: PMC3288335.
  • Viatte S, Plant D, Han B, et al. Association of HLA-DRB1 haplotypes with rheumatoid arthritis severity, mortality, and treatment response. JAMA. 2015;313(16):1645–1656. PubMed PMID: 25919528; PubMed Central PMCID: PMC4928097.
  • Vang T, Liu WH, Delacroix L, et al. LYP inhibits T-cell activation when dissociated from CSK. Nat Chem Biol. 2012;8(5):437–446. PubMed PMID: 22426112; PubMed Central PMCID: PMC3329573.
  • He RJ, Yu ZH, Zhang RY, et al. Protein tyrosine phosphatases as potential therapeutic targets. Acta Pharmacol Sin. 2014;35(10):1227–1246. PubMed PMID: 25220640; PubMed Central PMCID: PMC4186993.
  • Bottini N, Musumeci L, Alonso A, et al. A functional variant of lymphoid tyrosine phosphatase is associated with type I diabetes. Nat Genet. 2004;36(4):337–338. PubMed PMID: 15004560.
  • Vang T, Congia M, Maci S MD, et al. Autoimmune-associated lymphoid tyrosine phosphatase is a gain-of-function variant. Nat Genet. 2005;37(12):1317–1319. PubMed PMID: 16273109.
  • Begovich AB, Carlton VE, Honigberg LA, et al. A missense single-nucleotide polymorphism in a gene encoding a protein tyrosine phosphatase (PTPN22) is associated with rheumatoid arthritis. Am J Hum Genet. 2004;75(2):330–337. PubMed PMID: 15208781; PubMed Central PMCID: PMC1216068.
  • Kyogoku C, Langefeld CD, Ortmann WA, et al. Genetic association of the R620W polymorphism of protein tyrosine phosphatase PTPN22 with human SLE. Am J Hum Genet. 2004;75(3):504–507. PubMed PMID: 15273934; PubMed Central PMCID: PMC1182029.
  • Bowes J, Loehr S, Budu-Aggrey A, et al. PTPN22 is associated with susceptibility to psoriatic arthritis but not psoriasis: evidence for a further PsA-specific risk locus. Ann Rheum Dis. 2015;74(10):1882–1885. PubMed PMID: 25923216; PubMed Central PMCID: PMC4602265.
  • Canton I, Akhtar S, Gavalas NG, et al. A single-nucleotide polymorphism in the gene encoding lymphoid protein tyrosine phosphatase (PTPN22) confers susceptibility to generalised vitiligo. Genes Immun. 2005;6(7):584–587. PubMed PMID: 16015369.
  • Criswell LA, Pfeiffer KA, Lum RF, et al. Analysis of families in the multiple autoimmune disease genetics consortium (MADGC) collection: the PTPN22 620W allele associates with multiple autoimmune phenotypes. Am J Hum Genet. 2005;76(4):561–571. PubMed PMID: 15719322; PubMed Central PMCID: PMC1199294.
  • Diaz-Gallo LM, Gourh P, Broen J, et al. Analysis of the influence of PTPN22 gene polymorphisms in systemic sclerosis. Ann Rheum Dis. 2011;70(3):454–462. PubMed PMID: 21131644; PubMed Central PMCID: PMC3170726.
  • D’Silva KJ, Zamora MB, Gerlach J, et al. Increased representation of the PTPN22 mutation in patients with immune thrombocytopenia. J Thromb Haemost. 2010;8(9):2076–2078. PubMed PMID: 20553389.
  • Kemp EH, McDonagh AJ, Wengraf DA, et al. The non-synonymous C1858T substitution in the PTPN22 gene is associated with susceptibility to the severe forms of alopecia areata. Hum Immunol. 2006;67(7):535–539. PubMed PMID: 16829308.
  • Martorana D, Maritati F, Malerba G, et al. PTPN22 R620W polymorphism in the ANCA-associated vasculitides. Rheumatology (Oxford). 2012;51(5):805–812. PubMed PMID: 22237046.
  • Skinningsrud B, Husebye ES, Gervin K, et al. Mutation screening of PTPN22: association of the 1858T-allele with Addison’s disease. Eur J Hum Genet. 2008;16(8):977–982. PubMed PMID: 18301444.
  • Vandiedonck C, Capdevielle C, Giraud M, et al. Association of the PTPN22*R620W polymorphism with autoimmune myasthenia gravis. Ann Neurol. 2006;59(2):404–407. PubMed PMID: 16437561.
  • Velaga MR, Wilson V, Jennings CE, et al. The codon 620 tryptophan allele of the lymphoid tyrosine phosphatase (LYP) gene is a major determinant of Graves’ disease. J Clin Endocrinol Metab. 2004;89(11):5862–5865. PubMed PMID: 15531553.
  • Viken MK, Amundsen SS, Kvien TK, et al. Association analysis of the 1858C>T polymorphism in the PTPN22 gene in juvenile idiopathic arthritis and other autoimmune diseases. Genes Immun. 2005;6(3):271–273. PubMed PMID: 15759012.
  • Serrano A, Marquez A, Mackie SL, et al. Identification of the PTPN22 functional variant R620W as susceptibility genetic factor for giant cell arteritis. Ann Rheum Dis. 2013;72(11):1882–1886. PubMed PMID: 23946333; PubMed Central PMCID: PMC4053592.
  • Rueda B, Nunez C, Orozco G, et al. C1858T functional variant of PTPN22 gene is not associated with celiac disease genetic predisposition. Hum Immunol. 2005;66(7):848–852. PubMed PMID: 16112033.
  • Matesanz F, Rueda B, Orozco G, et al. Protein tyrosine phosphatase gene (PTPN22) polymorphism in multiple sclerosis. J Neurol. 2005;252(8):994–995. PubMed PMID: 15765267.
  • Martin MC, Oliver J, Urcelay E, et al. The functional genetic variation in the PTPN22 gene has a negligible effect on the susceptibility to develop inflammatory bowel disease. Tissue Antigens. 2005;66(4):314–317. PubMed PMID: 16185327.
  • Ortiz-Fernandez L, Montes-Cano MA, Garcia-Lozano JR, et al. PTPN22 is not associated with Behcet’s disease. Study spanning the complete gene region in the Spanish population and meta-analysis of the functional variant R620W. Clin Exp Rheumatol. 2016;34(6 Suppl 102):S41–S45. PubMed PMID: 27050764.
  • Cenit MC, Marquez A, Cordero-Coma M, et al. Lack of association between the protein tyrosine phosphatase non-receptor type 22 R263Q and R620W functional genetic variants and endogenous non-anterior uveitis. Mol Vis. 2013;19:638–643. PubMed PMID: 23559857; PubMed Central PMCID: PMC3611931.
  • Lopez-Mejias R, Genre F, Remuzgo-Martinez S, et al. Role of PTPN22 and CSK gene polymorphisms as predictors of susceptibility and clinical heterogeneity in patients with Henoch-Schonlein purpura (IgA vasculitis). Arthritis Res Ther. 2015;17:286. 10.1186/s13075-015-0796-x. PubMed PMID: 26458874; PubMed Central PMCID: PMC4603645.
  • Boechat AL, Ogusku MM, Sadahiro A, et al. Association between the PTPN22 1858C/T gene polymorphism and tuberculosis resistance. Infect Genet Evol. 2013;16:310–313. PubMed PMID: 23499775.
  • Stanford SM, Bottini N. PTPN22: the archetypal non-HLA autoimmunity gene. Nat Rev Rheumatol. 2014;10(10):602–611. PubMed PMID: 25003765; PubMed Central PMCID: PMC4375551.
  • Lamsyah H, Rueda B, Baassi L, et al. Association of PTPN22 gene functional variants with development of pulmonary tuberculosis in Moroccan population. Tissue Antigens. 2009;74(3):228–232. PubMed PMID: 19563523.
  • WTCC Consortium. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature. 2007;447(7145):661–678. PubMed PMID: 17554300; PubMed Central PMCID: PMC2719288.
  • Gregersen PK, Amos CI, Lee AT, et al. 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(7):820–823. PubMed PMID: 19503088; PubMed Central PMCID: PMC2705058.
  • Stahl EA, Raychaudhuri S, Remmers EF, et al. Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci. Nat Genet. 2010;42(6):508–514. PubMed PMID: 20453842; PubMed Central PMCID: PMC4243840.
  • Orozco G, Viatte S, Bowes J, et al. Novel rheumatoid arthritis susceptibility locus at 22q12 identified in an extended UK genome-wide association study. Arthritis Rheumatol. 2014;66(1):24–30. PubMed PMID: 24449572; PubMed Central PMCID: PMC4285161.
  • Kim K, Bang SY, Lee HS, et al. High-density genotyping of immune loci in Koreans and Europeans identifies eight new rheumatoid arthritis risk loci. Ann Rheum Dis. 2015;74(3):e13. PubMed PMID: 24532676; PubMed Central PMCID: PMC4467986.
  • Eyre S, Bowes J, Diogo D, et al. High-density genetic mapping identifies new susceptibility loci for rheumatoid arthritis. Nat Genet. 2012;44(12):1336–1340. PubMed PMID: 23143596; PubMed Central PMCID: PMC3605761.
  • Torres-Carrillo NM, Ruiz-Noa Y, Martinez-Bonilla GE, et al. The +1858C/T PTPN22 gene polymorphism confers genetic susceptibility to rheumatoid arthritis in Mexican population from the Western Mexico. Immunol Lett. 2012;147:41–46. PubMed PMID: 22743847.
  • Kallberg H, Padyukov L, Plenge RM, et al. Gene-gene and gene-environment interactions involving HLA-DRB1, PTPN22, and smoking in two subsets of rheumatoid arthritis. Am J Hum Genet. 2007;80(5):867–875. PubMed PMID: 17436241; PubMed Central PMCID: PMC1852748.
  • Morgan AW, Thomson W, Martin SG, et al. Reevaluation of the interaction between HLA-DRB1 shared epitope alleles, PTPN22, and smoking in determining susceptibility to autoantibody-positive and autoantibody-negative rheumatoid arthritis in a large UK Caucasian population. Arthritis Rheum. 2009;60(9):2565–2576. PubMed PMID: 19714585.
  • Padyukov L, Seielstad M, Ong RT, et al. A genome-wide association study suggests contrasting associations in ACPA-positive versus ACPA-negative rheumatoid arthritis. Ann Rheum Dis. 2011;70(2):259–265. PubMed PMID: 21156761; PubMed Central PMCID: PMC3015094.
  • Bossini-Castillo L, de Kovel C, Kallberg H, et al. A genome-wide association study of rheumatoid arthritis without antibodies against citrullinated peptides. Ann Rheum Dis. 2015;74(3):e15. PubMed PMID: 24532677.
  • Terao C, Ohmura K, Kochi Y, et al. Anti-citrullinated peptide/protein antibody (ACPA)-negative RA shares a large proportion of susceptibility loci with ACPA-positive RA: a meta-analysis of genome-wide association study in a Japanese population. Arthritis Res Ther. 2015;17:104. 10.1186/s13075-015-0623-4. PubMed PMID: 25927497; PubMed Central PMCID: PMC4431175.
  • Jiang L, Yin J, Ye L, et al. Novel risk loci for rheumatoid arthritis in Han Chinese and congruence with risk variants in Europeans. Arthritis Rheumatol. 2014;66(5):1121–1132. PubMed PMID: 24782177.
  • Munoz-Valle JF, Padilla-Gutierrez JR, Hernandez-Bello J, et al. PTPN22-1123G>C polymorphism and anti-cyclic citrullinated protein antibodies in rheumatoid arthritis. Med Clin (Barc). 2017;149:95–100. PubMed PMID: 28291534.
  • Frisell T, Holmqvist M, Kallberg H, et al. Familial risks and heritability of rheumatoid arthritis: role of rheumatoid factor/anti-citrullinated protein antibody status, number and type of affected relatives, sex, and age. Arthritis Rheum. 2013;65(11):2773–2782. PubMed PMID: 23897126.
  • Kurreeman F, Liao K, Chibnik L, et al. Genetic basis of autoantibody positive and negative rheumatoid arthritis risk in a multi-ethnic cohort derived from electronic health records. Am J Hum Genet. 2011;88(1):57–69. PubMed PMID: 21211616; PubMed Central PMCID: PMC3014362.
  • Carmona FD, Mackie SL, Martin JE, et al. A large-scale genetic analysis reveals a strong contribution of the HLA class II region to giant cell arteritis susceptibility. Am J Hum Genet. 2015;96(4):565–580. PubMed PMID: 25817017; PubMed Central PMCID: PMC4385191.
  • Totaro MC, Tolusso B, Napolioni V, et al. PTPN22 1858C>T polymorphism distribution in Europe and association with rheumatoid arthritis: case-control study and meta-analysis. PLoS One. 2011;6(9):e24292. PubMed PMID: 21949702; PubMed Central PMCID: PMC3174938.
  • Burn GL, Svensson L, Sanchez-Blanco C, et al. Why is PTPN22 a good candidate susceptibility gene for autoimmune disease? FEBS Lett. 2011;585(23):3689–3698. PubMed PMID: 21515266.
  • Rodriguez-Rodriguez L, Taib WR, Topless R, et al. The PTPN22 R263Q polymorphism is a risk factor for rheumatoid arthritis in Caucasian case-control samples. Arthritis Rheum. 2011;63(2):365–372. PubMed PMID: 21279993.
  • Lopez-Cano DJ, Cadena-Sandoval D, Beltran-Ramirez O, et al. The PTPN22 R263Q polymorphism confers protection against systemic lupus erythematosus and rheumatoid arthritis, while PTPN22 R620W confers susceptibility to Graves’ disease in a Mexican population. Inflamm Res. 2017;66(9):775–781. 10.1007/s00011-017-1056-0. PubMed PMID: 28500376.
  • Orru V, Tsai SJ, Rueda B, et al. A loss-of-function variant of PTPN22 is associated with reduced risk of systemic lupus erythematosus. Hum Mol Genet. 2009;18(3):569–579. PubMed PMID: 18981062; PubMed Central PMCID: PMC2722189.
  • Diaz-Gallo LM, Espino-Paisan L, Fransen K, et al. Differential association of two PTPN22 coding variants with Crohn’s disease and ulcerative colitis. Inflamm Bowel Dis. 2011;17(11):2287–2294. PubMed PMID: 21287672.
  • Carlton VE, Hu X, Chokkalingam AP, et al. PTPN22 genetic variation: evidence for multiple variants associated with rheumatoid arthritis. Am J Hum Genet. 2005;77(4):567–581. PubMed PMID: 16175503; PubMed Central PMCID: PMC1275606.
  • Martin JE, Alizadeh BZ, Gonzalez-Gay MA, et al. Evidence for PTPN22 R620W polymorphism as the sole common risk variant for rheumatoid arthritis in the 1p13.2 region. J Rheumatol. 2011;38(11):2290–2296. PubMed PMID: 21965649.
  • Wan Taib WR, Smyth DJ, Merriman ME, et al. The PTPN22 locus and rheumatoid arthritis: no evidence for an effect on risk independent of Arg620Trp. PLoS One. 2010;5(10):e13544. PubMed PMID: 20975833; PubMed Central PMCID: PMC2958827.
  • Ruiz-Noa Y, Padilla-Gutierrez JR, Hernandez-Bello J, et al. Association of PTPN22 Haplotypes (−1123G>C/+1858C>T) with rheumatoid arthritis in Western Mexican population. Int J Genomics. 2017;2017:8753498. PubMed PMID: 28210620; PubMed Central PMCID: PMC5292183.
  • Stanford SM, Rapini N, Bottini N. Regulation of TCR signalling by tyrosine phosphatases: from immune homeostasis to autoimmunity. Immunology. 2012;137(1):1–19. PubMed PMID: 22862552; PubMed Central PMCID: PMC3449242.
  • Davis SJ, van der Merwe PA. The kinetic-segregation model: TCR triggering and beyond. Nat Immunol. 2006;7(8):803–809. PubMed PMID: 16855606.
  • Diaz-Gallo LM, Martin J. PTPN22 splice forms: a new role in rheumatoid arthritis. Genome Med. 2012;4(2):13. PubMed PMID: 22364193; PubMed Central PMCID: PMC3392759.
  • Cohen S, Dadi H, Shaoul E, et al. Cloning and characterization of a lymphoid-specific, inducible human protein tyrosine phosphatase, Lyp. Blood. 1999;93(6):2013–2024. PubMed PMID: 10068674.
  • Ronninger M, Guo Y, Shchetynsky K, et al. The balance of expression of PTPN22 splice forms is significantly different in rheumatoid arthritis patients compared with controls. Genome Med. 2012;4(1):2. PubMed PMID: 22264340; PubMed Central PMCID: PMC3334550.
  • Rieck M, Arechiga A, Onengut-Gumuscu S, et al. Genetic variation in PTPN22 corresponds to altered function of T and B lymphocytes. J Immunol. 2007;179(7):4704–4710. PubMed PMID: 17878369.
  • Bottini N, Peterson EJ. Tyrosine phosphatase PTPN22: multifunctional regulator of immune signaling, development, and disease. Annu Rev Immunol. 2014;32:83–119. PubMed PMID: 24364806.
  • Rawlings DJ, Dai X, Buckner JH. The role of PTPN22 risk variant in the development of autoimmunity: finding common ground between mouse and human. J Immunol. 2015;194(7):2977–2984. PubMed PMID: 25795788; PubMed Central PMCID: PMC4369788.
  • Zhang J, N Z, Jiang Q, 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(9):902–907. PubMed PMID: 21841778.
  • Salmond RJ, Brownlie RJ, Morrison VL, et al. The tyrosine phosphatase PTPN22 discriminates weak self peptides from strong agonist TCR signals. Nat Immunol. 2014;15(9):875–883. PubMed PMID: 25108421; PubMed Central PMCID: PMC4148831.
  • Remuzgo-Martinez S, Genre F, Castaneda S, et al. Protein tyrosine phosphatase non-receptor 22 and C-Src tyrosine kinase genes are down-regulated in patients with rheumatoid arthritis. Sci Rep. 2017;7(1):10525. 10.1038/s41598-017-10915-9. PubMed PMID: 28874816; PubMed Central PMCID: PMC5585411.
  • Wang Y, Shaked I, Stanford SM, et al. The autoimmunity-associated gene PTPN22 potentiates toll-like receptor-driven, type 1 interferon-dependent immunity. Immunity. 2013;39(1):111–122. PubMed PMID: 23871208; PubMed Central PMCID: PMC3830738.
  • Chang HH, Dwivedi N, Nicholas AP, et al. The W620 polymorphism in PTPN22 disrupts its interaction with peptidylarginine deiminase type 4 and enhances citrullination and NETosis. Arthritis Rheumatol. 2015;67(9):2323–2334. PubMed PMID: 26019128.
  • Messemaker TC, Huizinga TW, Kurreeman F. Immunogenetics of rheumatoid arthritis: understanding functional implications. J Autoimmun. 2015;64:74–81. PubMed PMID: 26215034.
  • Du J, Qiao Y, Sun L, et al. Lymphoid-specific tyrosine phosphatase (Lyp): a potential drug target for treatment of autoimmune diseases. Curr Drug Targets. 2014;15(3):335–346. PubMed PMID: 24188455.
  • Hasegawa K, Martin F, Huang G, et al. PEST domain-enriched tyrosine phosphatase (PEP) regulation of effector/memory T cells. Science. 2004;303:685–689. PubMed PMID: 14752163.
  • Maine CJ, Hamilton-Williams EE, Cheung J, et al. PTPN22 alters the development of regulatory T cells in the thymus. J Immunol. 2012;188:5267–5275. PubMed PMID: 22539785; PubMed Central PMCID: PMC3358490.
  • Brownlie RJ, Miosge LA, Vassilakos D, et al. Lack of the phosphatase PTPN22 increases adhesion of murine regulatory T cells to improve their immunosuppressive function. Sci Signal. 2012;5:ra87. PubMed PMID: 23193160; PubMed Central PMCID: PMC5836999.
  • Maine CJ, Marquardt K, Cheung J, et al. PTPN22 controls the germinal center by influencing the numbers and activity of T follicular helper cells. J Immunol. 2014;192:1415–1424. PubMed PMID: 24453256; PubMed Central PMCID: PMC3933017.
  • Zikherman J, Hermiston M, Steiner D, et al. PTPN22 deficiency cooperates with the CD45 E613R allele to break tolerance on a non-autoimmune background. J Immunol. 2009;182:4093–4106. PubMed PMID: 19299707; PubMed Central PMCID: PMC2765978.
  • Zheng P, Kissler S. PTPN22 silencing in the NOD model indicates the type 1 diabetes-associated allele is not a loss-of-function variant. Diabetes. 2013;62:896–904. PubMed PMID: 23193190; PubMed Central PMCID: PMC3581188.
  • Yeh LT, Miaw SC, Lin MH, et al. Different modulation of Ptpn22 in effector and regulatory T cells leads to attenuation of autoimmune diabetes in transgenic nonobese diabetic mice. J Immunol. 2013;191:594–607. PubMed PMID: 23752610.
  • Dai X, James RG, Habib T, et al. A disease-associated PTPN22 variant promotes systemic autoimmunity in murine models. J Clin Invest. 2013;123:2024–2036. PubMed PMID: 23619366; PubMed Central PMCID: PMC3638909.
  • Wu DJ, Zhou W, Enouz S, et al. Autoimmunity-associated LYP-W620 does not impair thymic negative selection of autoreactive T cells. PLoS One. 2014;9:e86677. PubMed PMID: 24498279; PubMed Central PMCID: PMC3911918.
  • Sood S, Brownlie RJ, Garcia C, et al. Loss of the protein tyrosine phosphatase ptpn22 reduces mannan-induced autoimmune arthritis in SKG mice. J Immunol. 2016;197:429–440. PubMed PMID: 27288531; PubMed Central PMCID: PMC4932175.
  • Sakaguchi N, Takahashi T, Hata H, et al. Altered thymic T-cell selection due to a mutation of the ZAP-70 gene causes autoimmune arthritis in mice. Nature. 2003;426:454–460. PubMed PMID: 14647385.
  • Sakaguchi S, Sakaguchi N, Yoshitomi H, et al. Spontaneous development of autoimmune arthritis due to genetic anomaly of T cell signal transduction: part 1. Semin Immunol. 2006;18:199–206. PubMed PMID: 16713715.
  • Wu HJ, Ivanov II, Darce J, et al. Gut-residing segmented filamentous bacteria drive autoimmune arthritis via T helper 17 cells. Immunity. 2010;32:815–827. PubMed PMID: 20620945; PubMed Central PMCID: PMC2904693.
  • Ditzel HJ. The K/BxN mouse: a model of human inflammatory arthritis. Trends Mol Med. 2004;10:40–45. PubMed PMID: 14720585.
  • Wu J, Katrekar A, Honigberg LA, et al. Identification of substrates of human protein-tyrosine phosphatase PTPN22. J Biol Chem. 2006;281:11002–11010. PubMed PMID: 16461343.
  • Yu X, Sun JP, He Y, et al. Structure, inhibitor, and regulatory mechanism of Lyp, a lymphoid-specific tyrosine phosphatase implicated in autoimmune diseases. Proc Natl Acad Sci U S A. 2007;104(50):19767–19772. PubMed PMID: 18056643; PubMed Central PMCID: PMC2148373.
  • Xie Y, Liu Y, Gong G, et al. Discovery of a novel submicromolar inhibitor of the lymphoid specific tyrosine phosphatase. Bioorg Med Chem Lett. 2008;18(9):2840–2844. PubMed PMID: 18434147; PubMed Central PMCID: PMC2701911.
  • Wu S, Bottini M, Rickert RC, et al. In silico screening for PTPN22 inhibitors: active hits from an inactive phosphatase conformation. ChemMedChem. 2009;4(3):440–444. PubMed PMID: 19177473; PubMed Central PMCID: PMC3102533.
  • Vang T, Xie Y, Liu WH, et al. Inhibition of lymphoid tyrosine phosphatase by benzofuran salicylic acids. J Med Chem. 2011;54(2):562–571. PubMed PMID: 21190368; PubMed Central PMCID: PMC3025750.
  • Stanford SM, Krishnamurthy D, Falk MD, et al. Discovery of a novel series of inhibitors of lymphoid tyrosine phosphatase with activity in human T cells. J Med Chem. 2011;54(6):1640–1654. PubMed PMID: 21341673; PubMed Central PMCID: PMC3086468.
  • He Y, Liu S, Menon A, et al. A potent and selective small-molecule inhibitor for the lymphoid-specific tyrosine phosphatase (LYP), a target associated with autoimmune diseases. J Med Chem. 2013;56(12):4990–5008. PubMed PMID: 23713581; PubMed Central PMCID: PMC3711248.
  • Obiri DD, Flink N, Maier JV, et al. PEST-domain-enriched tyrosine phosphatase and glucocorticoids as regulators of anaphylaxis in mice. Allergy. 2012;67:175–182. PubMed PMID: 21981059.
  • Hou X, Li R, Li K, et al. Fast identification of novel lymphoid tyrosine phosphatase inhibitors using target-ligand interaction-based virtual screening. J Med Chem. 2014;57(22):9309–9322. PubMed PMID: 25372368.
  • Hou X, Li K, Yu X, et al. Protein flexibility in docking-based virtual screening: discovery of novel lymphoid-specific tyrosine phosphatase inhibitors using multiple crystal structures. J Chem Inf Model. 2015;55(9):1973–1983. PubMed PMID: 26360643.
  • Zheng K, Zhao Z, Lin N, et al. Protective effect of pinitol against inflammatory mediators of rheumatoid arthritis via inhibition of protein tyrosine phosphatase non-receptor type 22 (PTPN22). Med Sci Monit. 2017;23:1923–1932. PubMed PMID: 28430763; PubMed Central PMCID: PMC5408901.
  • Majorczyk E, Pawlik A, Kusnierczyk P. PTPN22 1858C>T polymorphism is strongly associated with rheumatoid arthritis but not with a response to methotrexate therapy. Int Immunopharmacol. 2010;10(12):1626–1629. PubMed PMID: 20888443.
  • Daien CI, Fabre S, Rittore C, et al. TGF beta1 polymorphisms are candidate predictors of the clinical response to rituximab in rheumatoid arthritis. Joint Bone Spine. 2012;79(5):471–475. PubMed PMID: 22129793.
  • Potter C, Hyrich KL, Tracey A, et al. Association of rheumatoid factor and anti-cyclic citrullinated peptide positivity, but not carriage of shared epitope or PTPN22 susceptibility variants, with anti-tumour necrosis factor response in rheumatoid arthritis. Ann Rheum Dis. 2009;68(1):69–74. PubMed PMID: 18375541; PubMed Central PMCID: PMC2596303.
  • Kokkonen H, Johansson M, Innala L, et al. The PTPN22 1858C/T polymorphism is associated with anti-cyclic citrullinated peptide antibody-positive early rheumatoid arthritis in northern Sweden. Arthritis Res Ther. 2007;9(3):R56. PubMed PMID: 17553139; PubMed Central PMCID: PMC2206338.
  • Kole R, Krainer AR, Altman S. RNA therapeutics: beyond RNA interference and antisense oligonucleotides. Nat Rev Drug Discov. 2012;11(2):125–140. PubMed PMID: 22262036; PubMed Central PMCID: PMC4743652.
  • Dermitzakis ET. From gene expression to disease risk. Nat Genet. 2008;40(5):492–493. PubMed PMID: 18443581.
  • Scherer LJ, Rossi JJ. Approaches for the sequence-specific knockdown of mRNA. Nat Biotechnol. 2003;21(12):1457–1465. PubMed PMID: 14647331.
  • Lam JK, Chow MY, Zhang Y, et al. siRNA versus miRNA as therapeutics for gene silencing. Mol Ther Nucleic Acids. 2015;4:e252. PubMed PMID: 26372022; PubMed Central PMCID: PMC4877448.
  • Watts JK, Corey DR. Silencing disease genes in the laboratory and the clinic. J Pathol. 2012;226(2):365–379. PubMed PMID: 22069063; PubMed Central PMCID: PMC3916955.
  • Lee SJ, Lee A, Hwang SR, et al. TNF-alpha gene silencing using polymerized siRNA/thiolated glycol chitosan nanoparticles for rheumatoid arthritis. Mol Ther. 2014;22(2):397–408. PubMed PMID: 24145554; PubMed Central PMCID: PMC3916041.
  • Delogu LG, Magrini A, Bergamaschi A, et al. Conjugation of antisense oligonucleotides to PEGylated carbon nanotubes enables efficient knockdown of PTPN22 in T lymphocytes. Bioconjug Chem. 2009;20(3):427–431. PubMed PMID: 19243140.
  • Ahmadi H, Ramezani M, Yazdian-Robati R, et al. Acute toxicity of functionalized single wall carbon nanotubes: A biochemical, histopathologic and proteomics approach. Chem Biol Interact. 2017;275:196–209. PubMed PMID: 28807745.
  • Perri V, Pellegrino M, Ceccacci F, et al. Use of short interfering RNA delivered by cationic liposomes to enable efficient down-regulation of PTPN22 gene in human T lymphocytes. PLoS One. 2017;12(4):e0175784. PubMed PMID: 28437437; PubMed Central PMCID: PMC5402975.
  • Barenholz Y. Doxil(R)–the first FDA-approved nano-drug: lessons learned. J Control Release. 2012;160(2):117–134. PubMed PMID: 22484195.
  • Wagner S, Peters O, Fels C, et al. Pegylated-liposomal doxorubicin and oral topotecan in eight children with relapsed high-grade malignant brain tumors. J Neurooncol. 2008;86(2):175–181. PubMed PMID: 17641821.
  • Cho JH, Feldman M. Heterogeneity of autoimmune diseases: pathophysiologic insights from genetics and implications for new therapies. Nat Med. 2015;21(7):730–738. PubMed PMID: 26121193; PubMed Central PMCID: PMC5716342.
  • Bosello S, Fedele AL, Peluso G, et al. Very early rheumatoid arthritis is the major predictor of major outcomes: clinical ACR remission and radiographic non-progression. Ann Rheum Dis. 2011;70(7):1292–1295. PubMed PMID: 21515600; PubMed Central PMCID: PMC3103665.
  • Senis YA, Barr AJ. Targeting receptor-type protein tyrosine phosphatases with biotherapeutics: is outside-in better than inside-out? Molecules. 2018;23:569. PubMed PMID: 29498714.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.