Biomarkers predicting a need for intensive treatment in patients with early arthritis

Current Pharmaceutical Design

Volumn 21, Issue 2, 2015, Pages 170-181

  Gonzalez Alvaro I ^a   Ortiz, A Ma ^a   Seoane, I V ^b   Garcia Vicuna R ^a   Martinez C ^b   Gomariz, R P ^b  

^a HOSPITAL UNIVERSITARIO DE LA PRINCESA   (Spain)

^b UNIVERSIDAD COMPLUTENSE DE MADRID   (Spain)

Author keywords

Biomarker; Early arthritis; IL 15; VIP

Indexed keywords

BIOLOGICAL MARKER; CYCLIC CITRULLINATED PEPTIDE ANTIBODY; DISEASE MODIFYING ANTIRHEUMATIC DRUG; HLA DRB1 ANTIGEN; INTERLEUKIN 15; NON RECEPTOR PROTEIN TYROSINE PHOSPHATASE 22; OSTEOCLAST DIFFERENTIATION FACTOR; OSTEOPROTEGERIN; RHEUMATOID FACTOR; STAT4 PROTEIN; VASOACTIVE INTESTINAL POLYPEPTIDE;

ALLELE; ANTIBODY DETECTION; ARTICLE; DAS28; DISEASE ACTIVITY; DISEASE ACTIVITY SCORE; EDUCATIONAL STATUS; GENDER BIAS; HEALTH ASSESSMENT QUESTIONNAIRE; HEALTH STATUS INDICATOR; HOSPITAL UNIVERSITARIO LA PRINCESA INDEX; HUMAN; INTENSIVE CARE; MARRIAGE; ONSET AGE; PRIORITY JOURNAL; PROGNOSIS; PROTEIN BLOOD LEVEL; RHEUMATOID ARTHRITIS; SEX DIFFERENCE; SINGLE NUCLEOTIDE POLYMORPHISM; SMOKING; METABOLISM; PATHOLOGY; SEVERITY OF ILLNESS INDEX;

ARTHRITIS, RHEUMATOID; BIOMARKERS; HUMANS; SEVERITY OF ILLNESS INDEX;

EID: 84925868080     PISSN: 13816128     EISSN: 18734286     Source Type: Journal    
DOI: 10.2174/1381612820666140825123104     Document Type: Article

References (106)

1. Carmona L, Cross M, Williams B, Lassere M, March L. Rheumatoid arthritis. Best Pract Res Clin Rheumatol 2010; 24: 733-45.
2. Scott DL, Wolfe F, Huizinga TW. Rheumatoid arthritis. Lancet 2010; 376: 1094-108.
3. Welsing PM, van Gestel AM, Swinkels HL, Kiemeney LA, van Riel PL. The relationship between disease activity, joint destruction, and functional capacity over the course of rheumatoid arthritis. Arthritis Rheum 2001; 44: 2009-17.
4. Bansback N, Marra CA, Finckh A, Anis A. The economics of treatment in early rheumatoid arthritis. Best Pract Res Clin Rheumatol 2009; 23: 83-92.
5. Lajas C, Abasolo L, Bellajdel B, et al. Costs and predictors of costs in rheumatoid arthritis: a prevalence-based study. Arthritis Rheum 2003; 49: 64-70.
6. Yelin E, Wanke LA. An assessment of the annual and long-term direct costs of rheumatoid arthritis: the impact of poor function and functional decline. Arthritis Rheum 1999; 42: 1209-18.
7. Lundkvist J, Kastang F, Kobelt G. The burden of rheumatoid arthritis and access to treatment: health burden and costs. Eur J Health Econ 2008; 8 Suppl 2: S49-60.
8. Alamanos Y, Drosos AA. Epidemiology of adult rheumatoid arthritis. Autoimmun Rev 2005; 4: 130-6.
9. Navarro-Cano G, Del Rincon I, Pogosian S, Roldan JF, Escalante A. Association of mortality with disease severity in rheumatoid arthritis, independent of comorbidity. Arthritis Rheum 2003; 48: 2425-33.
10. Pincus T, Callahan LF, Sale WG, Brooks AL, Payne LE, Vaughn WK. Severe functional declines, work disability, and increased mortality in seventy-five rheumatoid arthritis patients studied over nine years. Arthritis Rheum 1984; 27: 864-72.
11. Sokka T, Abelson B, Pincus T. Mortality in rheumatoid arthritis: 2008 update. Clin Exp Rheumatol 2008; 26(5 Suppl 51): S35-61.
12. Bergstrom U, Book C, Lindroth Y, Marsal L, Saxne T, Jacobsson L. Lower disease activity and disability in Swedish patients with rheumatoid arthritis in 1995 compared with 1978. Scand J Rheumatol 1999; 28: 160-5.
13. Pincus T, Brooks RH, Callahan LF. Prediction of long-term mortality in patients with rheumatoid arthritis according to simple questionnaire and joint count measures. Ann Intern Med 1994; 120: 26-34.
14. Healey LA, Wilske KR. Reforming the pyramid. A plan for treating rheumatoid arthritis in the 1990s. Rheum Dis Clin North Am 1989; 15: 615-9.
15. Wilske KR, Healey LA. Remodeling the pyramid--a concept whose time has come. J Rheumatol 1989; 16: 565-7.
16. Hess EV, Luggen ME. Remodeling the pyramid--a concept whose time has not yet come. J Rheumatol 1989; 16: 1175-6.
17. McCarty DJ. Suppress rheumatoid inflammation early and leave the pyramid to the Egyptians. J Rheumatol 1990; 17: 1115-8.
18. O'Dell JR. Treating rheumatoid arthritis early: a window of opportunity? Arthritis Rheum 2002; 46: 283-5.
19. Anderson JJ, Wells G, Verhoeven AC, Felson DT. Factors predicting response to treatment in rheumatoid arthritis: the importance of disease duration. Arthritis Rheum 2000; 43: 22-9.
20. Nell VP, Machold KP, Eberl G, Stamm TA, Uffmann M, Smolen JS. Benefit of very early referral and very early therapy with disease-modifying anti-rheumatic drugs in patients with early rheumatoid arthritis. Rheumatology (Oxford) 2004; 43: 906-14.
21. Gremese E, Salaffi F, Bosello SL, et al. Very early rheumatoid arthritis as a predictor of remission: a multicentre real life prospective study. Ann Rheum Dis 2013; 72: 858-62.
22. Aletaha D, Breedveld FC, Smolen JS. The need for new classification criteria for rheumatoid arthritis. Arthritis Rheum 2005; 52: 3333-6.
23. Aletaha D, Neogi T, Silman AJ, et al. 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Ann Rheum Dis 2010; 69: 1580-8.
24. Verstappen SM, McCoy MJ, Roberts C, Dale NE, Hassell AB, Symmons DP. Beneficial effects of a 3-week course of intramuscular glucocorticoid injections in patients with very early inflammatory polyarthritis: results of the STIVEA trial. Ann Rheum Dis 2010; 69: 503-9.
25. Emery P, Durez P, Dougados M, et al. Impact of T-cell costimulation modulation in patients with undifferentiated inflammatory arthritis or very early rheumatoid arthritis: a clinical and imaging study of abatacept (the ADJUST trial). Ann Rheum Dis 2010; 69: 510-6.
26. Saleem B, Mackie S, Quinn M, et al. Does the use of tumour necrosis factor antagonist therapy in poor prognosis, undifferentiated arthritis prevent progression to rheumatoid arthritis? Ann Rheum Dis 2008; 67: 1178-80.
27. Quinn MA, Green MJ, Marzo-Ortega H, et al. Prognostic factors in a large cohort of patients with early undifferentiated inflammatory arthritis after application of a structured management protocol. Arthritis Rheum 2003; 48: 3039-45.
28. Raza K, Filer A. Predicting the development of RA in patients with early undifferentiated arthritis. Best Pract Res Clin Rheumatol 2009; 23: 25-36.
29. van der Helm-van Mil AH, le Cessie S, van Dongen H, Breedveld FC, Toes RE, Huizinga TW. A prediction rule for disease outcome in patients with recent-onset undifferentiated arthritis: how to guide individual treatment decisions. Arthritis Rheum 2007; 56: 433-40.
30. Verpoort KN, van Dongen H, Allaart CF, Toes RE, Breedveld FC, Huizinga TW. Undifferentiated arthritis--disease course assessed in several inception cohorts. Clin Exp Rheumatol 2004; 22(5 Suppl 35): S12-7.
31. Hernandez-Garcia C, Vargas E, Abasolo L, et al. Lag time between onset of symptoms and access to rheumatology care and DMARD therapy in a cohort of patients with rheumatoid arthritis. J Rheumatol 2000; 27: 2323-8.
32. Gonzalez-Alvaro I, Hernandez-Garcia C. El estudio emAR. Variabilidad en el uso de recursos terapéuticos. emAR Estudio sobre el manejo de la Artritis Reumatoide. Barcelona: TINGS Servicios de Comunicación 2001; 92-128.
33. Villaverde V, Descalzo MA, Carmona L, Bascones M, Carbonell J. Characteristics of early arthritis units that may be associated with better referral efficiency: survey of SERAP units. Reumatol Clin 2011; 7: 236-40.
34. Descalzo MA, Carbonell J, Gonzalez-Alvaro I, et al. Effectiveness of a clinical practice intervention in early rheumatoid arthritis. Arthritis Care Res 2012; 64: 321-30.
35. Grigor C, Capell H, Stirling A, et al. Effect of a treatment strategy of tight control for rheumatoid arthritis (the TICORA study): a single-blind randomised controlled trial. Lancet 2004; 364: 263-9.
36. Allaart CF, Breedveld FC, Dijkmans BA. Treatment of recentonset rheumatoid arthritis: lessons from the BeSt study. J Rheumatol Suppl 2007; 80: 25-33.
37. Mottonen T, Hannonen P, Leirisalo-Repo M, et al. Comparison of combination therapy with single-drug therapy in early rheumatoid arthritis: a randomised trial. FIN-RACo trial group. Lancet 1999; 353: 1568-73.
38. Verstappen SM, Jacobs JW, van der Veen MJ, et al. Intensive treatment with methotrexate in early rheumatoid arthritis: aiming for remission. Computer Assisted Management in Early Rheumatoid Arthritis (CAMERA, an open-label strategy trial). Ann Rheum Dis 2007; 66: 1443-9.
39. Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Allaart CF, et al. Clinical and radiographic outcomes of four different treatment strategies in patients with early rheumatoid arthritis (the BeSt study): a randomized, controlled trial. Arthritis Rheum 2005; 52: 3381-90.
40. Gonzalez-Alvaro I, Hernandez-Garcia C, Villaverde Garcia V, Vargas E, Ortiz AM. Variations in the drug treatment of rheumatoid arthritis in Spain. Med Clin (Barc) 2002; 118: 771-6.
41. Zink A, Listing J, Ziemer S, Zeidler H. Practice variation in the treatment of rheumatoid arthritis among German rheumatologists. J Rheumatol 2001; 28: 2201-8.
42. Sokka T, Envalds M, Pincus T. Treatment of rheumatoid arthritis: a global perspective on the use of antirheumatic drugs. Mod Rheumatol 2008; 18: 228-39.
43. Smolen JS, Aletaha D, Bijlsma JW, et al. Treating rheumatoid arthritis to target: recommendations of an international task force. Ann Rheum Dis 2010; 69: 631-7.
44. Huizinga TW, van der Helm-van Mil A. A quantitative approach to early rheumatoid arthritis. Bull Hosp Jt Dis 2011; 69: 116-21.
45. Boers M. Understanding the window of opportunity concept in early rheumatoid arthritis. Arthritis Rheum 2003; 48: 1771-4.
46. Schellekens GA, de Jong BA, van den Hoogen FH, van de Putte LB, van Venrooij WJ. Citrulline is an essential constituent of antigenic determinants recognized by rheumatoid arthritis-specific autoantibodies. J Clin Invest 1998; 101: 273-81.
47. Schellekens GA, Visser H, de Jong BA, et al. The diagnostic properties of rheumatoid arthritis antibodies recognizing a cyclic citrullinated peptide. Arthritis Rheum 2000; 43: 155-63.
48. Verstappen SM, Lunt M, Bunn DK, Scott DG, Symmons DP. In patients with early inflammatory polyarthritis, ACPA positivity, younger age and inefficacy of the first non-biological DMARD are predictors for receiving biological therapy: results from the Norfolk Arthritis Register. Ann Rheum Dis 2011; 70: 1428-32.
49. Gonzalez-Alvaro I, Ortiz AM, Alvaro-Gracia JM, et al. Interleukin 15 levels in serum may predict a severe disease course in patients with early arthritis. PLoS One 2011; 6: e29492.
50. Felson DT, Anderson JJ, Meenan RF. Use of short-term efficacy/toxicity tradeoffs to select second-line drugs in rheumatoid arthritis. A metaanalysis of published clinical trials. Arthritis Rheum 1992; 35: 1117-25.
51. Laan RF, van Riel PL, van de Putte LB. Leflunomide and methotrexate. Curr Opin Rheumatol 2001; 13: 159-63.
52. Alarcon GS. Epidemiology of rheumatoid arthritis. Rheum Dis Clin North Am 1995; 21: 589-604.
53. Leeb BF, Haindl PM, Maktari A, Nothnagl T, Rintelen B. Disease activity score-28 values differ considerably depending on patient's pain perception and sex. J Rheumatol 2007; 34: 2382-7.
54. Ahlmen M, Svensson B, Albertsson K, Forslind K, Hafstrom I. Influence of gender on assessments of disease activity and function in early rheumatoid arthritis in relation to radiographic joint damage. Ann Rheum Dis 2010; 69: 230-3.
55. Castrejon I, Carmona L, Ortiz AM, Belmonte MA, Martinez-Lopez JA, Gonzalez-Alvaro I. Development and validation of a new disease activity index as a numerical sum of four variables in patients with early arthritis. Arthritis Care Res 2013; 65: 518-25.
56. Pease CT, Bhakta BB, Devlin J, Emery P. Does the age of onset of rheumatoid arthritis influence phenotype?: a prospective study of outcome and prognostic factors. Rheumatology (Oxford) 1999; 38: 228-34.
57. Huscher D, Sengler C, Gromnica-Ihle E, et al. Clinical presentation, burden of disease and treatment in young-onset and late-onset rheumatoid arthritis: a matched-pairs analysis taking age and disease duration into account. Clin Exp Rheumatol 2013; 31: 256-62.
58. DeWitt EM, Lin L, Glick HA, Anstrom KJ, Schulman KA, Reed SD. Pattern and predictors of the initiation of biologic agents for the treatment of rheumatoid arthritis in the United States: an analysis using a large observational data bank. Clin Ther 2009; 31: 1871-80.
59. Dixon WG, Abrahamowicz M, Beauchamp ME, et al. Immediate and delayed impact of oral glucocorticoid therapy on risk of serious infection in older patients with rheumatoid arthritis: a nested casecontrol analysis. Ann Rheum Dis 2012; 71: 1128-33.
60. Listing J, Gerhold K, Zink A. The risk of infections associated with rheumatoid arthritis, with its comorbidity and treatment. Rheumatology (Oxford) 2013; 52: 53-61.
61. Winthrop KL. Infections and biologic therapy in rheumatoid arthritis: our changing understanding of risk and prevention. Rheum Dis Clin North Am 2012; 38: 727-45.
62. Visser H, le Cessie S, Vos K, Breedveld FC, Hazes JM. How to diagnose rheumatoid arthritis early: a prediction model for persistent (erosive) arthritis. Arthritis Rheum 2002; 46: 357-65.
63. Emery P, Dorner T. Optimising treatment in rheumatoid arthritis: a review of potential biological markers of response. Ann Rheum Dis 2011; 70: 2063-70.
64. Gonzalez-Alvaro I, Descalzo MA, Carmona L. Trends towards an improved disease state in rheumatoid arthritis over time: influence of new therapies and changes in management approach: analysis of the EMECAR cohort. Arthritis Res Ther 2008; 10: R138.
65. Michaud K, Wallenstein G, Wolfe F. Treatment and nontreatment predictors of health assessment questionnaire disability progression in rheumatoid arthritis: a longitudinal study of 18,485 patients. Arthritis Care Res 2011; 63: 366-72.
66. Louie GH, Reveille JD, Ward MM. Challenges comparing functional limitations in rheumatoid arthritis and ankylosing spondylitis. Clin Exp Rheumatol 2009; 27(4 Suppl 55):S83-91.
67. Robinson WH, Lindstrom TM, Cheung RK, Sokolove J. Mechanistic biomarkers for clinical decision making in rheumatic diseases. Nat Rev Rheumatol 2013; 9: 267-76.
68. Gonzalez-Alvaro I, Ortiz AM, Tomero EG, et al. Baseline serum RANKL levels may serve to predict remission in rheumatoid arthritis patients treated with TNF antagonists. Ann Rheum Dis 2007; 66: 1675-8.
69. Ziolkowska M, Kurowska M, Radzikowska A, et al. High levels of osteoprotegerin and soluble receptor activator of nuclear factor kappa B ligand in serum of rheumatoid arthritis patients and their normalization after anti-tumor necrosis factor alpha treatment. Arthritis Rheum 2002; 46: 1744-53.
70. Crotti TN, Smith MD, Weedon H, et al. Receptor activator NFkappaB ligand (RANKL) expression in synovial tissue from patients with rheumatoid arthritis, spondyloarthropathy, osteoarthritis, and from normal patients: semiquantitative and quantitative analysis. Ann Rheum Dis 2002; 61: 1047-54.
71. Geusens PP, Landewe RB, Garnero P, et al. The ratio of circulating osteoprotegerin to RANKL in early rheumatoid arthritis predicts later joint destruction. Arthritis Rheum 2006; 54: 1772-7.
72. Cho ML, Ju JH, Kim KW, et al. Cyclosporine A inhibits IL-15- induced IL-17 production in CD4+ T cells via down-regulation of PI3K/Akt and NF-kappaB. Immunol Lett 2007; 108:88-96.
73. Gonzalez-Alvaro I, Ortiz Garcia AM, Dominguez-Jimenez C, et al. Inhibition of TNF and IL-17 production by leflunomide involves the JAK/STAT pathway. Ann Rheum Dis 2009; 68: 1644-50.
74. Yoshihara K, Yamada H, Hori A, Yajima T, Kubo C, Yoshikai Y. IL-15 exacerbates collagen-induced arthritis with an enhanced CD4+ T cell response to produce IL-17. Eur J Immunol 2007; 37: 2744-52.
75. Ziolkowska M, Koc A, Luszczykiewicz G, et al. High levels of IL- 17 in rheumatoid arthritis patients: IL-15 triggers in vitro IL-17 production via cyclosporin A-sensitive mechanism. J Immunol 2000; 164: 2832-8.
76. Gonzalez-Alvaro I, Dominguez-Jimenez C, Ortiz AM, et al. Interleukin-15 and interferon-gamma participate in the cross-talk between natural killer and monocytic cells required for tumour necrosis factor production. Arthritis Res Ther 2006; 8: R88.
77. McInnes IB, Leung BP, Sturrock RD, Field M, Liew FY. Interleukin-15 mediates T cell-dependent regulation of tumor necrosis factor-alpha production in rheumatoid arthritis [see comments]. Nat Med 1997; 3: 189-95.
78. Miranda-Carus ME, Balsa A, Benito-Miguel M, Perez de Ayala C, Martin-Mola E. IL-15 and the initiation of cell contact-dependent synovial fibroblast-T lymphocyte cross-talk in rheumatoid arthritis: effect of methotrexate. J Immunol 2004; 173: 1463-76.
79. Benito-Miguel M, Garcia-Carmona Y, Balsa A, et al. IL-15 Expression on RA Synovial Fibroblasts Promotes B Cell Survival. PLoS One 2012; 7:e40620.
80. Carroll HP, Paunovic V, Gadina M. Signalling, inflammation and arthritis: Crossed signals: the role of interleukin-15 and -18 in autoimmunity. Rheumatology (Oxford) 2008; 47: 1269-77.
81. Liu CC, Perussia B, Young JD. The emerging role of IL-15 in NKcell development. Immunol Today 2000; 21: 113-6.
82. Miranda-Carus ME, Benito-Miguel M, Balsa A, et al. Peripheral blood T lymphocytes from patients with early rheumatoid arthritis express RANKL and interleukin-15 on the cell surface and promote osteoclastogenesis in autologous monocytes. Arthritis Rheum 2006; 54: 1151-64.
83. Ogata Y, Kukita A, Kukita T, et al. A novel role of IL-15 in the development of osteoclasts: inability to replace its activity with IL- 2. J Immunol 1999; 162: 2754-60.
84. Schett G, Hayer S, Zwerina J, Redlich K, Smolen JS. Mechanisms of Disease: the link between RANKL and arthritic bone disease. Nat Clin Prac Rheumatol 2005; 1: 47-54.
85. Knevel R, Krabben A, Brouwer E, et al. Genetic variants in IL15 associate with progression of joint destruction in rheumatoid arthritis: a multicohort study. Ann Rheum Dis 2012; 71: 1651-7.
86. Ruchatz H, Leung BP, Wei XQ, McInnes IB, Liew FY. Soluble IL- 15 receptor alpha-chain administration prevents murine collageninduced arthritis: a role for IL-15 in development of antigeninduced immunopathology. J Immunol 1998; 160: 5654-60.
87. Baslund B, Tvede N, Danneskiold-Samsoe B, et al. Targeting interleukin-15 in patients with rheumatoid arthritis: A proof-ofconcept study. Arthritis Rheum 2005; 52: 2686-92.
88. Lamana A, Ortiz AM, Alvaro-Gracia JM, et al. Characterization of serum interleukin-15 in healthy volunteers and patients with early arthritis to assess its potential use as a biomarker. Eur Cytokine Netw 2010; 21: 186-94.
89. Abad C, Gomariz RP, Waschek JA. Neuropeptide mimetics and antagonists in the treatment of inflammatory disease: focus on VIP and PACAP. Curr Top Med Chem 2006; 6: 151-63.
90. Gomariz RP, Juarranz Y, Abad C, Arranz A, Leceta J, Martinez C. VIP-PACAP system in immunity: new insights for multitarget therapy. Ann N Y Acad Sci 2006; 1070: 51-74.
91. Gonzalez-Rey E, Ganea D, Delgado M. Neuropeptides: keeping the balance between pathogen immunity and immune tolerance. Curr Opin Pharmacol 2010; 10: 473-81.
92. Gomariz RP, Gutierrez-Canas I, Arranz A, et al. Peptides targeting Toll-like receptor signalling pathways for novel immune therapeutics. Curr Pharm Des 2010; 16: 1063-80.
93. Delgado M, Abad C, Martinez C, Leceta J, Gomariz RP. Vasoactive intestinal peptide prevents experimental arthritis by downregulating both autoimmune and inflammatory components of the disease. Nat Med 2001; 7: 563-8.
94. Juarranz Y, Abad C, Martinez C, et al. Protective effect of vasoactive intestinal peptide on bone destruction in the collageninduced arthritis model of rheumatoid arthritis. Arthritis Res Ther 2005; 7: R1034-45.
95. Leceta J, Gomariz RP, Martinez C, Carrion M, Arranz A, Juarranz Y. Vasoactive intestinal peptide regulates Th17 function in autoimmune inflammation. Neuroimmunomodulation 2007; 14: 134-8.
96. Gutierrez-Canas I, Juarranz Y, Santiago B, et al. VIP downregulates TLR4 expression and TLR4-mediated chemokine production in human rheumatoid synovial fibroblasts. Rheumatology (Oxford) 2006; 45: 527-32.
97. Gutierrez-Canas I, Juarranz Y, Santiago B, et al. Immunoregulatory properties of vasoactive intestinal peptide in human T cell subsets: implications for rheumatoid arthritis. Brain Behav Immun 2008; 22: 312-7.
98. Carrion M, Juarranz Y, Perez-Garcia S, et al. RNA sensors in human osteoarthritis and rheumatoid arthritis synovial fibroblasts: immune regulation by vasoactive intestinal peptide. Arthritis Rheum 2011; 63: 1626-36.
99. Perez-Garcia S, Juarranz Y, Carrion M, et al. Mapping the CRFurocortins system in human osteoarthritic and rheumatoid synovial fibroblasts: effect of vasoactive intestinal peptide. J Cell Physiol 2011; 226: 3261-9.
100. Carrion M, Juarranz Y, Martinez C, et al. IL-22/IL-22R1 axis and S100A8/A9 alarmins in human osteoarthritic and rheumatoid arthritis synovial fibroblasts. Rheumatology (Oxford) 2013; 52: 2177-86.
101. Juarranz Y, Gutierrez-Canas I, Santiago B, Carrion M, Pablos JL, Gomariz RP. Differential expression of vasoactive intestinal peptide and its functional receptors in human osteoarthritic and rheumatoid synovial fibroblasts. Arthritis Rheum 2008; 58: 1086- 95.
102. Jiang W, Gao SG, Chen XG, et al. Expression of synovial fluid and articular cartilage VIP in human osteoarthritic knee: a new indicator of disease severity? Clin Biochem 2012; 45: 1607-12.
103. El-Sayed ZA, Mostafa GA, Aly GS, El-Shahed GS, El-Aziz MM, El-Emam SM. Cardiovascular autonomic function assessed by autonomic function tests and serum autonomic neuropeptides inEgyptian children and adolescents with rheumatic diseases. Rheumatology (Oxford) 2009; 48: 843-8.
104. Martinez C, Ortiz AM, Juarranz Y, et al. Serum levels of vasoactive intestinal Peptide as a prognostic marker in early arthritis. PLoS One 2014; 9: e85248.
105. Lamana A, Balsa A, Rueda B, et al. The TT Genotype of the STAT4 rs7574865 Polymorphism Is Associated with High DiseaseActivity and Disability in Patients with Early Arthritis. PLoS One 2012; 7: e43661.
106. Burn GL, Svensson L, Sanchez-Blanco C, Saini M, Cope AP. Why is PTPN22 a good candidate susceptibility gene for autoimmune disease? FEBS Lett 2011; 585: 3689-98.