Top

Published in:

01-06-2010 | Review

Bacterial and human peptidylarginine deiminases: targets for inhibiting the autoimmune response in rheumatoid arthritis?

Authors: Pamela Mangat, Natalia Wegner, Patrick J Venables, Jan Potempa

Published in: Arthritis Research & Therapy | Issue 3/2010

Abstract

Peptidylarginine deiminases (PADs) convert arginine within a peptide (peptidylarginine) into peptidylcitrulline. Citrullination by human PADs is important in normal physiology and inflammation. Porphyromonas gingivalis, a major pathogen in periodontitis, is the only prokaryote described to possess PAD. P. gingivalis infection may generate citrullinated peptides, which trigger anti-citrullinated peptide antibodies. In susceptible individuals, host protein citrullination by human PADs in the joint probably perpetuates antibody formation, paving the way for the development of chronic arthritis. Blockades of bacterial and human PADs may act as powerful novel therapies by inhibiting the generation of the antigens that trigger and sustain autoimmunity in rheumatoid arthritis.

Available only for authorised users

Wegner N, Lundberg K, Kinloch A, Fisher B, Malmström V, Feldmann M, Venables PJ: Autoimmunity to specific citrullinated proteins gives the first clues to the etiology of rheumatoid arthritis. Immunol Rev. 2010, 233: 34-54. 10.1111/j.0105-2896.2009.00850.x.CrossRefPubMed

Schellekens GA, Visser H, de Jong BA, Hoogen van den FH, Hazes JM, Breedveld FC, van Venrooij WJ: The diagnostic properties of rheumatoid arthritis antibodies recognizing a cyclic citrullinated peptide. Arthritis Rheum. 2000, 43: 155-163. 10.1002/1529-0131(200001)43:1<155::AID-ANR20>3.0.CO;2-3.CrossRefPubMed

Chavanas S, Mechin MC, Takahara H, Kawada A, Nachat R, Serre G, Simon M: Comparative analysis of the mouse and human peptidylarginine deiminase gene clusters reveals highly conserved non-coding segments and a new human gene, PADI6. Gene. 2004, 330: 19-27. 10.1016/j.gene.2003.12.038.CrossRefPubMed

McGraw WT, Potempa J, Farley D, Travis J: Purification, characterization, and sequence analysis of a potential virulence factor from Porphyromonas gingivalis, peptidylarginine deiminase. Infect Immun. 1999, 67: 3248-3256.PubMedCentralPubMed

Vossenaar ER, Smeets TJ, Kraan MC, Raats JM, van Venrooij WJ, Tak PP: The presence of citrullinated proteins is not specific for rheumatoid synovial tissue. Arthritis Rheum. 2004, 50: 3485-3494. 10.1002/art.20584.CrossRefPubMed

Nielen MM, van Schaardenburg D, Reesink HW, Stadt van de RJ, Horst-Bruinsma van der IE, de Koning MH, Habibuw MR, Vandenbroucke JP, Dijkmans BA: Specific autoantibodies precede the symptoms of rheumatoid arthritis: a study of serial measurements in blood donors. Arthritis Rheum. 2004, 50: 380-386. 10.1002/art.20018.CrossRefPubMed

Rosenstein ED, Greenwald RA, Kushner LJ, Weissmann G: Hypothesis: the humoral immune response to oral bacteria provides a stimulus for the development of rheumatoid arthritis. Inflammation. 2004, 28: 311-318. 10.1007/s10753-004-6641-z.CrossRefPubMed

Lundberg K, Kinloch A, Fisher BA, Wegner N, Wait R, Charles P, Mikuls TR, Venables PJ: Antibodies to citrullinated alpha-enolase peptide 1 are specific for rheumatoid arthritis and cross-react with bacterial enolase. Arthritis Rheum. 2008, 58: 3009-3019. 10.1002/art.23936.CrossRefPubMed

de Pablo P, Chapple IL, Buckley CD, Dietrich T: Periodontitis in systemic rheumatic diseases. Nat Rev Rheumatol. 2009, 5: 218-224. 10.1038/nrrheum.2009.28.CrossRefPubMed

10.

Borrell LN, Burt BA, Taylor GW: Prevalence and trends in periodontitis in the USA: the [corrected] NHANES, 1988 to 2000. J Dent Res. 2005, 84: 924-930. 10.1177/154405910508401010.CrossRefPubMed

11.

de Pablo P, Dietrich T, McAlindon TE: Association of periodontal disease and tooth loss with rheumatoid arthritis in the US population. J Rheumatol. 2008, 35: 70-76.PubMed

12.

Mercado F, Marshall RI, Klestov AC, Bartold PM: Is there a relationship between rheumatoid arthritis and periodontal disease?. J Clin Periodontol. 2000, 27: 267-272. 10.1034/j.1600-051x.2000.027004267.x.CrossRefPubMed

13.

Socransky SS, Haffajee AD: Periodontal microbial ecology. Periodontol 2000. 2005, 38: 135-187. 10.1111/j.1600-0757.2005.00107.x.CrossRefPubMed

14.

Tatakis DN, Kumar PS: Etiology and pathogenesis of periodontal diseases. Dent Clin North Am. 2005, 49: 491-516. 10.1016/j.cden.2005.03.001.CrossRefPubMed

15.

Mikuls TR, Payne JB, Reinhardt RA, Thiele GM, Maziarz E, Cannella AC, Holers VM, Kuhn KA, O'Dell JR: Antibody responses to Porphyromonas gingivalis (P. gingivalis) in subjects with rheumatoid arthritis and periodontitis. Int Immunopharmacol. 2009, 9: 38-42. 10.1016/j.intimp.2008.09.008.PubMedCentralCrossRefPubMed

16.

Moen K, Brun JG, Madland TM, Tynning T, Jonsson R: Immunoglobulin G and A antibody responses to Bacteroides forsythus and Prevotella intermedia in sera and synovial fluids of arthritis patients. Clin Diagn Lab Immunol. 2003, 10: 1043-1050.PubMedCentralPubMed

17.

Moen K, Brun JG, Valen M, Skartveit L, Eribe EK, Olsen I, Jonsson R: Synovial inflammation in active rheumatoid arthritis and psoriatic arthritis facilitates trapping of a variety of oral bacterial DNAs. Clin Exp Rheumatol. 2006, 24: 656-663.PubMed

18.

Ogrendik M, Kokino S, Ozdemir F, Bird PS, Hamlet S: Serum antibodies to oral anaerobic bacteria in patients with rheumatoid arthritis. MedGenMed. 2005, 7: 2-PubMedCentralPubMed

19.

Martinez-Martinez RE, Abud-Mendoza C, Patino-Marin N, Rizo-Rodriguez JC, Little JW, Loyola-Rodriguez JP: Detection of periodontal bacterial DNA in serum and synovial fluid in refractory rheumatoid arthritis patients. J Clin Periodontol. 2009, 36: 1004-1010. 10.1111/j.1600-051X.2009.01496.x.CrossRefPubMed

20.

Ogrendik M: Treatment of rheumatoid arthritis with ornidazole: a randomized, double-blind, placebo-controlled study. Rheumatol Int. 2006, 26: 1132-1137. 10.1007/s00296-006-0145-0.CrossRefPubMed

21.

Ogrendik M: Levofloxacin treatment in patients with rheumatoid arthritis receiving methotrexate. South Med J. 2007, 100: 135-139.CrossRefPubMed

22.

Ogrendik M: Effects of clarithromycin in patients with active rheumatoid arthritis. Curr Med Res Opin. 2007, 23: 515-522. 10.1185/030079906X167642.CrossRefPubMed

23.

O'Dell JR, Haire CE, Palmer W, Drymalski W, Wees S, Blakely K, Churchill M, Eckhoff PJ, Weaver A, Doud D, Erikson N, Dietz F, Olson R, Maloley P, Klassen LW, Moore GF: Treatment of early rheumatoid arthritis with minocycline or placebo: results of a randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 1997, 40: 842-848. 10.1002/art.1780400510.CrossRefPubMed

24.

Kloppenburg M, Breedveld FC, Terwiel JP, Mallee C, Dijkmans BA: Minocycline in active rheumatoid arthritis. A double-blind, placebo-controlled trial. Arthritis Rheum. 1994, 37: 629-636. 10.1002/art.1780370505.CrossRefPubMed

25.

Amin AR, Attur MG, Thakker GD, Patel PD, Vyas PR, Patel RN, Patel IR, Abramson SB: A novel mechanism of action of tetracyclines: effects on nitric oxide synthases. Proc Natl Acad Sci USA. 1996, 93: 14014-14019. 10.1073/pnas.93.24.14014.PubMedCentralCrossRefPubMed

26.

Greenwald RA, Golub LM, Lavietes B, Ramamurthy NS, Gruber B, Laskin RS, McNamara TF: Tetracyclines inhibit human synovial collagenase in vivo and in vitro. J Rheumatol. 1987, 14: 28-32.PubMed

27.

Chen M, Ona VO, Li M, Ferrante RJ, Fink KB, Zhu S, Bian J, Guo L, Farrell LA, Hersch SM, Hobbs W, Vonsattel JP, Cha JH, Friedlander RM: Minocycline inhibits caspase-1 and caspase-3 expression and delays mortality in a transgenic mouse model of Huntington disease. Nat Med. 2000, 6: 797-801. 10.1038/80538.CrossRefPubMed

28.

Knuckley B, Luo Y, Thompson PR: Profiling Protein Arginine Deiminase 4 (PAD4): a novel screen to identify PAD4 inhibitors. Bioorg Med Chem. 2008, 16: 739-745. 10.1016/j.bmc.2007.10.021.PubMedCentralCrossRefPubMed

29.

Imamura T, Matsushita K, Travis J, Potempa J: Inhibition of trypsin-like cysteine proteinases (gingipains) from Porphyromonas gingivalis by tetracycline and its analogues. Antimicrob Agents Chemother. 2001, 45: 2871-2876. 10.1128/AAC.45.10.2871-2876.2001.PubMedCentralCrossRefPubMed

30.

Jang B, Kim E, Choi JK, Jin JK, Kim JI, Ishigami A, Maruyama N, Carp RI, Kim YS, Choi EK: Accumulation of citrullinated proteins by up-regulated peptidylarginine deiminase 2 in brains of scrapie-infected mice: a possible role in pathogenesis. Am J Pathol. 2008, 173: 1129-1142. 10.2353/ajpath.2008.080388.PubMedCentralCrossRefPubMed

31.

Gyorgy B, Toth E, Tarcsa E, Falus A, Buzas EI: Citrullination: a posttranslational modification in health and disease. Int J Biochem Cell Biol. 2006, 38: 1662-1677. 10.1016/j.biocel.2006.03.008.CrossRefPubMed

32.

Young DS, Meersman F, Oxley D, Webster J, Gill AC, Bronstein I, Lowe CR, Dear DV: Effect of enzymatic deimination on the conformation of recombinant prion protein. Biochim Biophys Acta. 2009, 1794: 1123-1133.CrossRefPubMed

33.

Neeli I, Dwivedi N, Khan S, Radic M: Regulation of extracellular chromatin release from neutrophils. J Innate Immun. 2009, 1: 194-201. 10.1159/000206974.CrossRefPubMed

34.

Wang Y, Li M, Stadler S, Correll S, Li P, Wang D, Hayama R, Leonelli L, Han H, Grigoryev SA, Allis CD, Coonrod SA: Histone hypercitrullination mediates chromatin decondensation and neutrophil extracellular trap formation. J Cell Biol. 2009, 184: 205-213. 10.1083/jcb.200806072.PubMedCentralCrossRefPubMed

35.

Tanikawa C, Ueda K, Nakagawa H, Yoshida N, Nakamura Y, Matsuda K: Regulation of protein Citrullination through p53/PADI4 network in DNA damage response. Cancer Res. 2009, 69: 8761-8769. 10.1158/0008-5472.CAN-09-2280.CrossRefPubMed

36.

Neeli I, Khan SN, Radic M: Histone deimination as a response to inflammatory stimuli in neutrophils. J Immunol. 2008, 180: 1895-1902.CrossRefPubMed

37.

Proost P, Loos T, Mortier A, Schutyser E, Gouwy M, Noppen S, Dillen C, Ronsse I, Conings R, Struyf S, Opdenakker G, Maudgal PC, Van Damme J: Citrullination of CXCL8 by peptidylarginine deiminase alters receptor usage, prevents proteolysis, and dampens tissue inflammation. J Exp Med. 2008, 205: 2085-2097. 10.1084/jem.20080305.PubMedCentralCrossRefPubMed

38.

Loos T, Mortier A, Gouwy M, Ronsse I, Put W, Lenaerts JP, Van Damme J, Proost P: Citrullination of CXCL10 and CXCL11 by peptidylarginine deiminase: a naturally occurring posttranslational modification of chemokines and new dimension of immunoregulation. Blood. 2008, 112: 2648-2656. 10.1182/blood-2008-04-149039.CrossRefPubMed

39.

Okumura N, Haneishi A, Terasawa F: Citrullinated fibrinogen shows defects in FPA and FPB release and fibrin polymerization catalyzed by thrombin. Clin Chim Acta. 2009, 401: 119-123. 10.1016/j.cca.2008.12.002.CrossRefPubMed

40.

Chang X, Yamada R, Sawada T, Suzuki A, Kochi Y, Yamamoto K: The inhibition of antithrombin by peptidylarginine deiminase 4 may contribute to pathogenesis of rheumatoid arthritis. Rheumatology (Oxford). 2005, 44: 293-298. 10.1093/rheumatology/keh473.CrossRef

41.

Chapuy-Regaud S, Sebbag M, Baeten D, Clavel C, Foulquier C, De Keyser F, Serre G: Fibrin deimination in synovial tissue is not specific for rheumatoid arthritis but commonly occurs during synovitides. J Immunol. 2005, 174: 5057-5064.CrossRefPubMed

42.

Suzuki A, Yamada R, Yamamoto K: Citrullination by peptidylarginine deiminase in rheumatoid arthritis. Ann N Y Acad Sci. 2007, 1108: 323-339. 10.1196/annals.1422.034.CrossRefPubMed

43.

Suzuki A, Yamada R, Chang X, Tokuhiro S, Sawada T, Suzuki M, Nagasaki M, Nakayama-Hamada M, Kawaida R, Ono M, Ohtsuki M, Furukawa H, Yoshino S, Yukioka M, Tohma S, Matsubara T, Wakitani S, Teshima R, Nishioka Y, Sekine A, Iida A, Takahashi A, Tsunoda T, Nakamura Y, Yamamoto K: Functional haplotypes of PADI4, encoding citrullinating enzyme peptidylarginine deiminase 4, are associated with rheumatoid arthritis. Nat Genet. 2003, 34: 395-402. 10.1038/ng1206.CrossRefPubMed

44.

Foulquier C, Sebbag M, Clavel C, Chapuy-Regaud S, Al Badine R, Méchin MC, Vincent C, Nachat R, Yamada M, Takahara H, Simon M, Guerrin M, Serre G: Peptidyl arginine deiminase type 2 (PAD-2) and PAD-4 but not PAD-1, PAD-3, and PAD-6 are expressed in rheumatoid arthritis synovium in close association with tissue inflammation. Arthritis Rheum. 2007, 56: 3541-3553. 10.1002/art.22983.CrossRefPubMed

45.

Vossenaar ER, Radstake TR, Heijden van der A, van Mansum MA, Dieteren C, de Rooij DJ, Barrera P, Zendman AJ, van Venrooij WJ: Expression and activity of citrullinating peptidylarginine deiminase enzymes in monocytes and macrophages. Ann Rheum Dis. 2004, 63: 373-381. 10.1136/ard.2003.012211.PubMedCentralCrossRefPubMed

46.

Kinloch A, Lundberg K, Wait R, Wegner N, Lim NH, Zendman AJ, Saxne T, Malmstrom V, Venables PJ: Synovial fluid is a site of citrullination of autoantigens in inflammatory arthritis. Arthritis Rheum. 2008, 58: 2287-2295. 10.1002/art.23618.CrossRefPubMed

47.

Mastronardi FG, Wood DD, Mei J, Raijmakers R, Tseveleki V, Dosch HM, Probert L, Casaccia-Bonnefil P, Moscarello MA: Increased citrullination of histone H3 in multiple sclerosis brain and animal models of demyelination: a role for tumor necrosis factor-induced peptidylarginine deiminase 4 translocation. J Neurosci. 2006, 26: 11387-11396. 10.1523/JNEUROSCI.3349-06.2006.CrossRefPubMed

48.

Makrygiannakis D, af Klint E, Lundberg IE, Lofberg R, Ulfgren AK, Klareskog L, Catrina AI: Citrullination is an inflammation-dependent process. Ann Rheum Dis. 2006, 65: 1219-1222. 10.1136/ard.2005.049403.PubMedCentralCrossRefPubMed

49.

Galkin A, Kulakova L, Sarikaya E, Lim K, Howard A, Herzberg O: Structural insight into arginine degradation by arginine deiminase, an antibacterial and parasite drug target. J Biol Chem. 2004, 279: 14001-14008. 10.1074/jbc.M313410200.CrossRefPubMed

50.

Shirai H, Mokrab Y, Mizuguchi K: The guanidino-group modifying enzymes: structural basis for their diversity and commonality. Proteins. 2006, 64: 1010-1023. 10.1002/prot.20863.CrossRefPubMed

51.

Arita K, Hashimoto H, Shimizu T, Nakashima K, Yamada M, Sato M: Structural basis for Ca(2+)-induced activation of human PAD4. Nat Struct Mol Biol. 2004, 11: 777-783. 10.1038/nsmb799.CrossRefPubMed

52.

Rodriguez SB, Stitt BL, Ash DE: Expression of peptidylarginine deiminase from Porphyromonas gingivalis in Escherichia coli: enzyme purification and characterization. Arch Biochem Biophys. 2009, 488: 14-22. 10.1016/j.abb.2009.06.010.PubMedCentralCrossRefPubMed

53.

Lourbakos A, Chinni C, Thompson P, Potempa J, Travis J, Mackie EJ, Pike RN: Cleavage and activation of proteinase-activated receptor-2 on human neutrophils by gingipain-R from Porphyromonas gingivalis. FEBS Lett. 1998, 435: 45-48. 10.1016/S0014-5793(98)01036-9.CrossRefPubMed

54.

Niederman R, Brunkhorst B, Smith S, Weinreb RN, Ryder MI: Ammonia as a potential mediator of adult human periodontal infection: inhibition of neutrophil function. Arch Oral Biol. 1990, 35 (Suppl): 205S-209S. 10.1016/0003-9969(90)90159-8.CrossRefPubMed

55.

Belotti D, Rieppi M, Nicoletti MI, Casazza AM, Fojo T, Taraboletti G, Giavazzi R: Paclitaxel (Taxol(R)) inhibits motility of paclitaxel-resistant human ovarian carcinoma cells. Clin Cancer Res. 1996, 2: 1725-1730.PubMed

56.

Pritzker LB, Moscarello MA: A novel microtubule independent effect of paclitaxel: the inhibition of peptidylarginine deiminase from bovine brain. Biochim Biophys Acta. 1998, 1388: 154-160.CrossRefPubMed

57.

Brahn E, Tang C, Banquerigo ML: Regression of collagen-induced arthritis with taxol, a microtubule stabilizer. Arthritis Rheum. 1994, 37: 839-845. 10.1002/art.1780370611.CrossRefPubMed

58.

ClinicalTrials.gov: search of: paclitaxel AND rheumatoid: a study using intravenous paxceed to treat patients with rheumatoid arthritis. [http://clinicaltrials.gov/ct2/results?term=paclitaxel+AND+rheumatoid]

59.

Luo Y, Arita K, Bhatia M, Knuckley B, Lee YH, Stallcup MR, Sato M, Thompson PR: Inhibitors and inactivators of protein arginine deiminase 4: functional and structural characterization. Biochemistry. 2006, 45: 11727-11736. 10.1021/bi061180d.PubMedCentralCrossRefPubMed

60.

Luo Y, Knuckley B, Lee YH, Stallcup MR, Thompson PR: A fluoroacetamidinebased inactivator of protein arginine deiminase 4: design, synthesis, and in vitro and in vivo evaluation. J Am Chem Soc. 2006, 128: 1092-1093. 10.1021/ja0576233.PubMedCentralCrossRefPubMed

61.

Stone EM, Schaller TH, Bianchi H, Person MD, Fast W: Inactivation of two diverse enzymes in the amidinotransferase superfamily by 2-chloroacetamidine: dimethylargininase and peptidylarginine deiminase. Biochemistry. 2005, 44: 13744-13752. 10.1021/bi051341y.CrossRefPubMed

62.

Willis V, Gizinski A, Knuckley B, Banda N, Cordova K, Luo Y, Causey C: Treatment with Cl-amidine, a peptidyl arginine deiminase (PAD) inhibitor significantly reduces collagen-induced arthritis (CIA) [abstract]. Arthritis Rheum. 2009, 60 (suppl 10): 665-

63.

Bhattacharya SK, Bhat MB, Takahara H: Modulation of peptidyl arginine deiminase 2 and implication for neurodegeneration. Curr Eye Res. 2006, 31: 1063-1071. 10.1080/02713680600991437.CrossRefPubMed

64.

Li L, Li Z, Chen D, Lu X, Feng X, Wright EC, Solberg NO, Dunaway-Mariano D, Mariano PS, Galkin A, Kulakova L, Herzberg O, Green-Church KB, Zhang L: Inactivation of microbial arginine deiminases by L-canavanine. J Am Chem Soc. 2008, 130: 1918-10.1021/ja0760877.CrossRefPubMed

65.

Frey C, Narayanan K, McMillan K, Spack L, Gross SS, Masters BS, Griffith OW: L-thiocitrulline. A stereospecific, heme-binding inhibitor of nitric-oxide synthases. J Biol Chem. 1994, 269: 26083-26091.PubMed

66.

Nachat R, Mechin MC, Takahara H, Chavanas S, Charveron M, Serre G, Simon M: Peptidylarginine deiminase isoforms 1-3 are expressed in the epidermis and involved in the deimination of K1 and filaggrin. J Invest Dermatol. 2005, 124: 384-393. 10.1111/j.0022-202X.2004.23568.x.CrossRefPubMed

67.

Nachat R, Mechin MC, Charveron M, Serre G, Constans J, Simon M: Peptidylarginine deiminase isoforms are differentially expressed in the anagen hair follicles and other human skin appendages. J Invest Dermatol. 2005, 125: 34-41. 10.1111/j.0022-202X.2005.23763.x.CrossRefPubMed

68.

Mechin MC, Enji M, Nachat R, Chavanas S, Charveron M, Ishida-Yamamoto A, Serre G, Takahara H, Simon M: The peptidylarginine deiminases expressed in human epidermis differ in their substrate specificities and subcellular locations. Cell Mol Life Sci. 2005, 62: 1984-1995. 10.1007/s00018-005-5196-y.CrossRefPubMed

69.

Sambandam T, Belousova M, Accaviti-Loper MA, Blanquicett C, Guercello V, Raijmakers R, Nicholas AP: Increased peptidylarginine deiminase type II in hypoxic astrocytes. Biochem Biophys Res Commun. 2004, 325: 1324-1329. 10.1016/j.bbrc.2004.10.173.CrossRefPubMed

70.

Ishigami A, Ohsawa T, Hiratsuka M, Taguchi H, Kobayashi S, Saito Y, Murayama S, Asaga H, Toda T, Kimura N, Maruyama N: Abnormal accumulation of citrullinated proteins catalyzed by peptidylarginine deiminase in hippocampal extracts from patients with Alzheimer's disease. J Neurosci Res. 2005, 80: 120-128. 10.1002/jnr.20431.CrossRefPubMed

71.

Urano Y, Watanabe K, Sakaki A, Arase S, Watanabe Y, Shigemi F, Takeda K, Akiyama K, Senshu T: Immunohistochemical demonstration of peptidylarginine deiminase in human sweat glands. Am J Dermatopathol. 1990, 12: 249-255. 10.1097/00000372-199006000-00005.CrossRefPubMed

72.

Ishigami A, Ohsawa T, Asaga H, Akiyama K, Kuramoto M, Maruyama N: Human peptidylarginine deiminase type II: molecular cloning, gene organization, and expression in human skin. Arch Biochem Biophys. 2002, 407: 25-31. 10.1016/S0003-9861(02)00516-7.CrossRefPubMed

73.

Vossenaar ER, Zendman AJ, van Venrooij WJ, Pruijn GJ: PAD, a growing family of citrullinating enzymes: genes, features and involvement in disease. Bioessays. 2003, 25: 1106-1118. 10.1002/bies.10357.CrossRefPubMed

74.

Hagiwara T, Nakashima K, Hirano H, Senshu T, Yamada M: Deimination of arginine residues in nucleophosmin/B23 and histones in HL-60 granulocytes. Biochem Biophys Res Commun. 2002, 290: 979-983. 10.1006/bbrc.2001.6303.CrossRefPubMed

Title: Bacterial and human peptidylarginine deiminases: targets for inhibiting the autoimmune response in rheumatoid arthritis?
Authors: Pamela Mangat
Natalia Wegner
Patrick J Venables
Jan Potempa
Publication date: 01-06-2010
Publisher: BioMed Central
Published in: Arthritis Research & Therapy / Issue 3/2010
Electronic ISSN: 1478-6362
DOI: https://doi.org/10.1186/ar3000

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 3/2010

Cell culture and passaging alters gene expression pattern and proliferation rate in rheumatoid arthritis synovial fibroblasts

Biomechanical modulation of collagen fragment-induced anabolic and catabolic activities in chondrocyte/agarose constructs

Treatment with apolipoprotein A-1 mimetic peptide reduces lupus-like manifestations in a murine lupus model of accelerated atherosclerosis

Plasma and synovial fluid microRNAs as potential biomarkers of rheumatoid arthritis and osteoarthritis

Transcriptional profiling of the nucleus pulposus: say yes to notochord

Obesity affects the chondrocyte responsiveness to leptin in patients with osteoarthritis

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

At a glance: The STEP trials