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The swollen joint, the thickened artery, and the smoking gun: tobacco exposure, citrullination and rheumatoid arthritis

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Abstract

Autoimmune diseases result from an interplay between susceptibility genes and environmental factors. These interacting etiopathogenetic components converge in a critical step preceding disease, the loss of tolerance to self. In this review, we examine the evidences linking tobacco smoking with the initiation and perpetuation of inflammation affecting both the synovial membrane and the endothelial lining in patients with rheumatoid arthritis. This disease is a compelling argument for the decisive role of environment in the triggering of a human autoimmune disease in genetically prone individuals.

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References

  1. Rioux JD, Abbas AK (2005) Paths to understanding the genetic basis of autoimmune disease. Nature 435:584–589

    Article  PubMed  CAS  Google Scholar 

  2. Klareskog L, Catrina AI, Paget S (2009) Rheumatoid arthritis. Lancet 373:659–672

    Article  PubMed  CAS  Google Scholar 

  3. Wallberg-Jonsson S, Johansson H, Ohman ML, Rantapaa-Dahlqvist S (1999) Extent of inflammation predicts cardiovascular disease and overall mortality in seropositive rheumatoid arthritis. A retrospective cohort study from disease onset. J Rheumatol 26:2562–2571

    PubMed  CAS  Google Scholar 

  4. Turesson C, O’Fallon WM, Crowson CS, Gabriel SE, Matteson EL (2002) Occurrence of extraarticular disease manifestations is associated with excess mortality in a community based cohort of patients with rheumatoid arthritis. J Rheumatol 29:62–67

    PubMed  Google Scholar 

  5. Solomon DH, Karlson EW, Rimm EB, Cannuscio CC, Mandl LA, Manson JE, Stampfer MJ, Curhan GC (2003) Cardiovascular morbidity and mortality in women diagnosed with rheumatoid arthritis. Circulation 107:1303–1307

    Article  PubMed  Google Scholar 

  6. Wolfe F, Freundlich B, Straus WL (2003) Increase in cardiovascular and cerebrovascular disease prevalence in rheumatoid arthritis. J Rheumatol 30:36–40

    PubMed  Google Scholar 

  7. Park YB, Ahn CW, Choi HK, Lee SH, In BH, Lee HC, Nam CM, Lee SK (2002) Atherosclerosis in rheumatoid arthritis: morphologic evidence obtained by carotid ultrasound. Arthritis Rheum 46:1714–1719

    Article  PubMed  Google Scholar 

  8. Jonsson SW, Backman C, Johnson O, Karp K, Lundstrom E, Sundqvist KG, Dahlqvist SR (2001) Increased prevalence of atherosclerosis in patients with medium term rheumatoid arthritis. J Rheumatol 28:2597–2602

    PubMed  CAS  Google Scholar 

  9. Goodson NJ, Wiles NJ, Lunt M, Barrett EM, Silman AJ, Symmons DP (2002) Mortality in early inflammatory polyarthritis: cardiovascular mortality is increased in seropositive patients. Arthritis Rheum 46:2010–2019

    Article  PubMed  Google Scholar 

  10. Hart JE, Laden F, Puett RF, Costenbader KH, Karlson EW (2009) Exposure to traffic pollution and increased risk of rheumatoid arthritis. Environ Health Perspect 117:1065–1069

    Article  PubMed  CAS  Google Scholar 

  11. Frostegård J (2002) Autoimmunity, oxidized LDL and cardiovascular disease. Autoimmun Rev 1:233–237

    Article  PubMed  Google Scholar 

  12. Elkan AC, Sjöberg B, Kolsrud B, Ringertz B, Hafström I, Frostegård J (2008) Gluten-free vegan diet induces decreased LDL and oxidized LDL levels and raised atheroprotective natural antibodies against phosphorylcholine in patients with rheumatoid arthritis: a randomized study. Arthritis Res Ther 10:R34

    Article  PubMed  Google Scholar 

  13. Situnayake RD, Kitas G (1997) Dyslipidemia and rheumatoid arthritis. Ann Rheum Dis 56:341–342

    Article  PubMed  CAS  Google Scholar 

  14. Symmons DP, Bankhead CR, Harrison BJ, Brennan P, Barrett EM, Scott DG et al (1997) Blood transfusion, smoking, and obesity as risk factors for the development of rheumatoid arthritis: results from a primary care-based incident case-control study in Norfolk, England. Arthritis Rheum 40:1955–1961

    Article  PubMed  CAS  Google Scholar 

  15. Voigt LF, Koepsell TD, Nelson JL, Dugowson CE, Daling JR (1994) Smoking, obesity, alcohol consumption, and the risk of rheumatoid arthritis. Epidemiology 5(5):525–532

    PubMed  CAS  Google Scholar 

  16. Georgiadis AN, Papavasiliou EC, Lourida ES, Alamanos Y, Kostara C, Tselepis AD, Drosos AA (2006) Atherogenic lipid profile is a feature characteristic of patients with early rheumatoid arthritis: effect of early treatment—a prospective, controlled study. Arthritis Res Ther 8:R82

    Article  PubMed  Google Scholar 

  17. Pemberton PW, Ahmad Y, Bodill H, Lokko D et al (2009) Biomarkers of oxidant stress, insulin sensitivity and endothelial activation in rheumatoid arthritis: a cross-sectional study of their association with accelerated atherosclerosis. BMC Res Notes 2:83

    Article  PubMed  Google Scholar 

  18. Hannawi S, Haluska B, Marwick TH, Thomas R (2007) Atherosclerotic disease is increased in recent-onset rheumatoid arthritis: a critical role for inflammation. Arthritis Res Ther 9:R116

    Article  PubMed  Google Scholar 

  19. Del Rincon I, O’Leary DH, Freeman GL, Escalante A (2007) Acceleration of atherosclerosis during the course of rheumatoid arthritis. Atherosclerosis 195:354–360

    Article  PubMed  CAS  Google Scholar 

  20. Del Rincon I, Williams K, Stern MP, Freeman GL, O’Leary DH, Escalante A (2003) Association between carotid atherosclerosis and markers of inflammation in rheumatoid arthritis patients and healthy subjects. Arthritis Rheum 48:1833–1840

    Article  PubMed  Google Scholar 

  21. Chung CP, Oeser A, Raggi P, Gebretsadik T, Shintani AK, Sokka T, Pincus T, Avalos I, Stein CM (2005) Increased coronary-artery atherosclerosis in rheumatoid arthritis: relationship to disease duration and cardiovascular risk factors. Arthritis Rheum 52:3045–3053

    Article  PubMed  Google Scholar 

  22. Turesson C, Jacobsson L, Bergström U (1999) Extra-articular rheumatoid arthritis: prevalence and mortality. Rheumatology (Oxford) 38:668–674

    Article  CAS  Google Scholar 

  23. Frostegård J (2005) Atherosclerosis in patients with autoimmune disorders. Arterioscler Thromb Vasc Biol 25:1776–1785

    Article  PubMed  Google Scholar 

  24. Klockars M, Koskela RS, Järvinen E, Kolari PJ, Rossi A (1987) Silica exposure and rheumatoid arthritis: a follow-up study of granite workers 1940–81. Br Med J 294:997–1000

    Article  CAS  Google Scholar 

  25. Caplan A (1959) Rheumatoid disease and pneumoconiosis. Proc R Soc Med 52:1111–1113

    PubMed  CAS  Google Scholar 

  26. Olsson AR, Skogh T, Wingren G (2001) Comorbidity and lifestyle, reproductive factors, and environmental exposures associated with rheumatoid arthritis. Ann Rheum Dis 60:934–939

    Article  Google Scholar 

  27. Pikwer M, Bergström U, Nilsson JÅ, Jacobsson L, Berglund G, Turesson C (2009) Breast feeding, but not use of oral contraceptives, is associated with reduced risk for rheumatoid arthritis. Ann Rheum Dis 68:526–530

    Article  PubMed  CAS  Google Scholar 

  28. Brun JG, Nilssen S, Kvale G (1995) Breast feeding, other reproductive factors and rheumatoid arthritis. A prospective study. Br J Rheumatol 34:542–546

    Article  PubMed  CAS  Google Scholar 

  29. Brennan P, Bankhead C, Silman A, Symmons D (1997) Oral contraceptives and rheumatoid arthritis: results from a primary care based incident case–control study. Semin Arthritis Rheum 26:817–823

    Article  PubMed  CAS  Google Scholar 

  30. Hazes JM, Dijkmans BA, Vanderbroucke JP, de Vries RR, Cats A (1990) Life style and the risk for rheumatoid arthritis: cigarette smoking and alcohol consumption. Ann Rheum Dis 49:980–982

    Article  PubMed  CAS  Google Scholar 

  31. Albano SA, Santana-Sahagun E, Weisman MH (2001) Cigarette smoking and rheumatoid arthritis. Semin Arthritis Rheum 31:146–159

    Article  PubMed  CAS  Google Scholar 

  32. Criswell LA, Merlino LA, Cerhan JR, Mikuls TR, Mudano AS, Burma M et al (2002) Cigarette smoking and the risk of rheumatoid arthritis among postmenopausal women: results from the Iowa Women’s Health Study. Am J Med 112:465–471

    Article  PubMed  Google Scholar 

  33. Tuomi T, Heliovaara M, Palosuo T, Aho K (1990) Smoking, lung function, and rheumatoid factors. Ann Rheum Dis 49:753–756

    Article  PubMed  CAS  Google Scholar 

  34. Vessey MP, Villard-Mackintosh L, Yeates D (1987) Oral contraceptives, cigarette smoking and other factors in relation to arthritis. Contraception 35:457–464

    Article  PubMed  CAS  Google Scholar 

  35. Uhlig T, Hagen KB, Kvien TK (1999) Current tobacco smoking, formal education, and the risk of rheumatoid arthritis. J Rheumatol 26:47–54

    PubMed  CAS  Google Scholar 

  36. Padyukov L, Silva C, Stolt P, Alfredsson L, Klareskog L (2004) A gene-environment interaction between smoking and shared epitope genes in HLA-DR provides a high risk of seropositive rheumatoid arthritis. Arthritis Rheum 50:3085–3092

    Article  PubMed  CAS  Google Scholar 

  37. Klareskog L, Stolt P, Lundberg K, Kallberg H, Bengtsson C, Grunewald J, et al., and the Epidemiological Investigation of Rheumatoid Arthritis Study Group (2006) A new model for an etiology of rheumatoid arthritis: smoking may trigger HLA–DR (shared epitope)–restricted immune reactions to autoantigens modified by citrullination. Arthritis Rheum 54:38–46

    Google Scholar 

  38. Hill JA, Southwood S, Sette A, Jevnikar AM, Bell DA, Cairns E (2003) Cutting edge: the conversion of arginine to citrulline allows for a high-affinity peptide interaction with the rheumatoid arthritis associated HLA-DRB1*0401 MHC class II molecule. J Immunol 171:538–541

    PubMed  CAS  Google Scholar 

  39. Pedersen M, Jacobsen S, Garred P et al (2007) Strong combined gene-environment effects in anti-cyclic citrullinated peptide-positive rheumatoid arthritis. A nation-wide case-control study in Denmark. Arthritis Rheum 56:1446–1453

    Article  PubMed  Google Scholar 

  40. Morgan AW, Thomson W, Martin SG et al (2009) 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 60:2565–2576

    Article  PubMed  Google Scholar 

  41. Michou L, Texeira VH, Pierlot C, Lasbleiz S, Bardin T, Dieudé P, Prum B, Comélis F, Petit-Texeira E (2008) Associations between genetic factors, tobacco smoking and autoantibodies in familial and sporadic rheumatoid arthritis. Ann Rheum Dis 67:466–470

    Article  PubMed  CAS  Google Scholar 

  42. Linn-Rasker SP, n Mil AH, van Gaalen FA, Kloppenburg M, de Vries RR, le Cessie S et al (2006) Smoking is a risk factor for anti-CCP antibodies only in rheumatoid arthritis patients who carry HLA-DRB1 shared epitope alleles. Ann Rheum Dis 65:366–371

    Article  PubMed  CAS  Google Scholar 

  43. Oliveira RD, Junta CM, Oliveira FR, Donadi EA, Louzada-Junior P (2008) Shared epitope, citrullinated cyclic peptide antibodies and smoking in Brazilian rheumatoid arthritis patients. Clin Rev Allergy Immunol 34:32–35

    Article  PubMed  Google Scholar 

  44. Mikuls TR, Hughes LB, Westfall AO et al (2008) Cigarette smoking, disease severity, and autoantibody expression in African Americans with recent-onset rheumatoid arthritis. Ann Rheum Dis 67:1529–1534

    Article  PubMed  CAS  Google Scholar 

  45. Lee HS, Irigoyen P, Kern M, Lee A, Batliwalla F, Khalli H et al (2007) Interaction between smoking, the shared epitope and anti-cyclic citrullinated peptide. A mixed picture in the three large North American Rheumatoid Arthritis cohorts. Arthritis Rheum 56:1745–1753

    Article  PubMed  CAS  Google Scholar 

  46. Silman AJ, Newman J, MacGregor A (1996) Cigarette smoking increases the risk for rheumatoid arthritis. Results from a nationwide study of disease-discordant twins. Arthritis Rheum 39:732–735

    Article  PubMed  CAS  Google Scholar 

  47. Másdóttir B, Jónsson T, Manfreosdóttir V et al (2000) Smoking, rheumatoid factor isotypes and severity of rheumatoid arthritis. Rheumatol 39:1202–1205

    Article  Google Scholar 

  48. Stolt P, Bengtsson C, Nordmark B, Lindbland S, Lundberg I, Klareskog L, Alfredsson L (2003) Quantification of the influence of cigarette smoking on rheumatoid arthritis: results from a population based case-control study, using incident cases. Ann Rheum Dis 62:835–841

    Article  PubMed  CAS  Google Scholar 

  49. Sverdrup B, Kallberg H, Bengtsson C, Lundberg I, Padyukov L, Alfredsson L et al (2005) Association between occupational exposure to mineral oil and rheumatoid arthritis: results from the Swedish EIRA case-control study. Arthritis Res Ther 7:R1296–R1303

    Article  PubMed  CAS  Google Scholar 

  50. Karlson EW, Chang S-C, Cui J et al (2010) Gene-environment interaction between smoking in predicting incident rheumatoid HLA-DRB1 shared epitope and heavy cigarette. Ann Rheum Dis 69:54–60

    Article  PubMed  CAS  Google Scholar 

  51. Sugiyama D, Nishimura K, Tamaki K, Tsuji G, Nakazawa T, Morinobu A, Kumagai S (2010) Impact of smoking as a risk factor for developing rheumatoid factor: a meta-analysis of observational studies. Ann Rheum Dis 69:70–81

    Article  PubMed  CAS  Google Scholar 

  52. Mattey DL, Hutchinson D, Dawes PT, Nixon NB, Clarke S, Fisher J, Brownfield A, Alldersea J, Fryer AA, Strange RC (2002) Smoking and disease severity in rheumatoid arthritis: association with polymorphism at the glutathione S-transferase M1 locus. Arthritis Rheum 46:640–646

    Article  PubMed  CAS  Google Scholar 

  53. Kim SJ, Kim MG, Kim KS, Song JS, Yim SB, Chung JH (2008) Impact of glutathione S-transferase M1 and T1 gene polymorphisms on the smoking-related coronary artery disease. J Korean Med Sci 23:365–372

    Article  PubMed  CAS  Google Scholar 

  54. Costenbader KH, Chang SC, De Vivo I, Plenge R, Karlson EW (2008) Genetic polymorphisms in PTPN22, PADI4, and CTLA4 and risk for rheumatoid arthritis. Arthritis Res Ther 10:R52

    Article  PubMed  Google Scholar 

  55. Mahdi H, Fisher BA, Källberg H, Plant D et al (2009) Specific interaction between genotype, smoking, and autoimmunity to citrullinated α-enolase in the etiology of rheumatoid arthritis. Nat Genet 41:1319–1324

    Article  PubMed  CAS  Google Scholar 

  56. Källberg H, Padyukov L, Plenge RM, Ronnelid J, Gregersen PK, n Mil AH et al (2007) Gene-gene and gene-environment interactions involving HLA-DRB1, PTPN22, and smoking in two subsets of rheumatoid arthritis. Am J Hum Genet 80:867–875

    Article  PubMed  Google Scholar 

  57. Plenge RM, Padyukov L, Remmers EF, Purcell S, Lee AT, Karlson EW, Wolfe F, Kastner DL, Alfredsson L, Altshuler D, Gregersen PK, Klareskog L, Rioux JD (2005) Replication of putative candidate-gene associations with rheumatoid arthritis in >4000 samples from North America and Sweden: association of susceptibility with PTPN22, CTLA4, and PADI4. Am J Hum Genet 77:1044–1060

    Article  PubMed  CAS  Google Scholar 

  58. Wesoly J, van der Helm-van Mil AH, Toes RE, Chokkalingam AP, Carlton VE, Begovich AB, Huizinga TW (2005) Association of the PTPN22 C1858T single-nucleotide polymorphism with rheumatoid arthritis phenotypes in an inception cohort. Arthritis Rheum 52:2948–2950

    Article  PubMed  CAS  Google Scholar 

  59. Shukla A, Timblin C, BeruBe K, Gordon T, McKinney W, Driscoll K, Vacek P, Mossman BT (2000) Inhaled particulate matter causes expression of nuclear factor (NF)-kappaB-related genes and oxidant-dependent NF-kappaB activation in vitro. Am J Respir Cell Mol Biol 23:182–187

    PubMed  CAS  Google Scholar 

  60. Makarov SS (2001) NF-kappa B in rheumatoid arthritis: a pivotal regulator of inflammation, hyperplasia, and tissue destruction. Arthritis Res 3:200–206

    Article  PubMed  CAS  Google Scholar 

  61. Jimenez LA, Drost EM, Gilmour PS, Rahman I, Antonicelli F, Ritchie H, MacNee W, Donaldson K (2002) PM(10)-exposed macrophages stimulate a proinflammatory response in lung epithelial cells via TNF-alpha. Am J Physiol Lung Cell Mol Physiol 282:L237–L248

    PubMed  CAS  Google Scholar 

  62. Kobayashi S, Momohara S, Kamatani N, Okamoto H (2008) Molecular aspects of rheumatoid factor: role of environmental factors. FEBS J 275:4456–4462

    Article  PubMed  CAS  Google Scholar 

  63. Tsurutani J, Castillo SS, Brognard J, Granville CA, Zhang C, Gills JJ, Sayyah J, Dennis PA (2005) Tobacco components stimulate Akt-dependent proliferation and NFkB-dependent survival in lung cancer cells. Carcinogenesis 26:1182–1195

    Article  PubMed  CAS  Google Scholar 

  64. García S, Liz M, Gómez-ReinoJJ Conde C (2010) Akt activity protects rheumatoid synovial fibroblasts from Fas-induced apoptosis by inhibition of Bid cleavage. Arthritis Res Ther 12(1):R33

    Article  PubMed  Google Scholar 

  65. Larsson L, Szponar B, Ridha B, Pehrson C, Dutkiewicz J, Krysińska-Traczyk E, Sitkowska J (2008) Identification of bacterial and fungal components in tobacco and tobacco smoke. Tob Induc Dis 4:4

    Article  PubMed  Google Scholar 

  66. Lundberg K, Nijenhuis S, Voosenaar ER, Palmblad K, van Venrooij WJ, Klareskog L, Zendman AJ, Harris HE (2005) Citrullinated proteins have increased immunogenicity and arthritogenicity and their presence in arthritic joints correlates with disease severity. Arthritis Res Ther 7:R458–R467

    Article  PubMed  CAS  Google Scholar 

  67. Kuhn KA, Kulik L, Tomooka B, Braschler KJ, Arend WP, Robinson WH, Holers VM (2006) Antibodies against citrullinated proteins enhance tissue injury in experimental autoimmune arthritis. J Clin Invest 116:961–973

    Article  PubMed  CAS  Google Scholar 

  68. Vossenaar ER, Robinson WH (2005) Citrullination and autoimmune disease: 8th Bertine Koperberg Meeting. Ann Rheum Dis 64:1513–1515

    Article  PubMed  CAS  Google Scholar 

  69. Gorman JD (2006) Smoking and rheumatoid arthritis: another reason to just say no. Arthritis Rheum 54:10–13

    Article  PubMed  CAS  Google Scholar 

  70. Masson-Bessiere C, Sebbag M, Girbal-Neuhauser E, Nogueira L, Vincent C, Senshu T, Serre G (2001) The major synovial targets of the rheumatoid arthritis-specific antifilaggrin autoantibodies are deiminated forms of the α- and β chains of fibrin. J Immunol 166:4177–4184

    PubMed  CAS  Google Scholar 

  71. Bang H, Egerer K, Gauliard A, Lüthke K, Rudulph PE, Fredenhagen G, Berg W, Feist E, Burmester G-R (2007) Mutation and citrullination modifies vimentin to a novel autoantigen in rheumatoid arthritis. Arthritis Rheum 56:2503–2511

    Article  PubMed  CAS  Google Scholar 

  72. Klareskog L, Rönnelid J, Lundberg K, Pdyukov L, Alfredsson L (2008) Immunity to citrullinated proteins in rheumatoid arthritis. Annu Rev Immunol 26:651–675

    Article  PubMed  CAS  Google Scholar 

  73. Takizawa Y, Suzuki A, Sawada T, Ohsaka TM, Inoue T, Yamada R, Yamamoto K (2006) Citrullinated fibrinogen detected as soluble citrullinated autoantigen in rheumatoid arthritis synovial fluids. Ann Rheum Dis 65:1013–1020

    Article  PubMed  CAS  Google Scholar 

  74. Shiozawa S, Hayashi S, Tsukamoto Y, Goko H, Kawasaki H, Wada T, Shimizu K, Yasuda N, Kamatani N, Takasugi K, Tanaka Y, Shiozawa K, Imura S (1998) Identification of the gene loci that predispose to rheumatoid arthritis. Int Immunol 10:1891–1895

    Article  PubMed  CAS  Google Scholar 

  75. Suzuki A, Yamada R, Chang X, Tokuhiro S, Sawada T, Suzuki M et al (2003) Functional haplotypes of PADI4, encoding citrullinating enzyme peptidylarginine deiminase 4, are associated with rheumatoid arthritis. Nat Genet 34:395–402

    Article  PubMed  CAS  Google Scholar 

  76. Makrygiannatis D, Hermansson M, Ulfgren AK, Nicholas AP, Zendman AJW, Eklund A, Grunewald J, Skold CM, Klareskog L, Catrina AI (2008) Smoking increases peptidylarginine deiminase 2 enzyme expression in human lungs and increases citrullination in BAL cells. Ann Rheum Dis 67:1488–1492

    Article  Google Scholar 

  77. Bongartz T, Cantaert T, Atkins SR, Harle P, Myers JL, Turesson C, Ryu JH, Baeten D, Matteson EL (2007) Citrullination in extra-articular manifestations of rheumatoid arthritis. Rheumatol 46:70–75

    Article  CAS  Google Scholar 

  78. Makrygiannatis D, Klint E, Lundberg IE, Löfberg R, Ulfgren AK, Klareskog L, Catrina AI (2006) Citrullination is an inflammation-dependent process. Ann Rheum Dis 65:1219–1222

    Article  Google Scholar 

  79. Tang WH, Wang Z, Cho L, Brennan DM, Hazen SL (2009) Diminished global arginine bioavailability and increased arginine catabolism as metabolic profile of increased cardiovascular risk. Am J Coll Cardiol 53:2061–2067

    Article  CAS  Google Scholar 

  80. Westhoff G, Rau R, Zink A (2008) Rheumatoid arthritis patients who smoke have a higher need for DMARDs and feel worse, but they do not have more joint damage than non-smokers of the same serological group. Rheumatol 47:849–854

    Article  CAS  Google Scholar 

  81. Mattey DL, Brownfield A, Dawes PT (2009) Relationship between pack-year history of smoking and response to tumor necrosis antagonists in patients with rheumatoid arthritis. J Rheumatol 36:1180–1187

    Article  PubMed  Google Scholar 

  82. Farragher TM, Goodson NJ, Naseem H, Silman AJ, Thomson W, Symmons D, Barton A (2008) Association of the HLA-DRB1 gene with premature death, particularly from cardiovascular disease, in patients with rheumatoid arthritis and inflammatory polyarthritis. Arthritis Rheum 58:359–369

    Article  PubMed  Google Scholar 

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Acknowledgments

We thank Jose R. Weisinger, M.D. for critical review of the manuscript.

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  1. Centro Nacional de Enfermedades Reumáticas, Division of Rheumatology, Hospital Universitario de Caracas, Apartado 4735, Caracas, 1010, Venezuela

    Natalí Serra-Bonett & Martín A. Rodríguez

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  1. Natalí Serra-Bonett
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Correspondence to Martín A. Rodríguez.

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Serra-Bonett, N., Rodríguez, M.A. The swollen joint, the thickened artery, and the smoking gun: tobacco exposure, citrullination and rheumatoid arthritis. Rheumatol Int 31, 567–572 (2011). https://doi.org/10.1007/s00296-010-1644-6

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