Abstract
Background: Overexpression and functional mutations of p53 have been found in the synovial tissue (ST) of patients with rheumatoid arthritis (RA), but their clinical significance remains unclear.
Objective: To analyse p53 expression in the ST of patients with RA and psoriatic arthritis (PsA) and its association with joint damage.
Methods: Synovial biopsy specimens were obtained by arthroscopy in 45 patients (27 RA, 18 PsA). Radiographs of hands, feet, and the joint undergoing arthroscopy were obtained to evaluate the presence of erosive disease. Synovial cell populations were analysed using CD4, CD8, CD138, CD20, and CD68 monoclonal antibodies (mAbs). The p53 protein was determined by immunohistology using DO7 mAb in 34 patients (18 RA, 16 PsA). In 11 patients with early RA, the association between p53 and 1 year progression of radiographic damage was analysed using the Larsen-Scott method.
Results: The p53 protein was detected in 16/18 (89%) patients with RA and in 9/16 (56%) patients with PsA, but its expression in RA was significantly higher than in PsA. In RA, p53 expression was significantly associated with erosive disease, and its scores were higher in patients with radiological progression. CD68 expression was also associated with erosions and radiological progression in RA. No association was found between either p53 or CD68 and erosive disease in PsA.
Conclusions: These results suggest that p53 ST overexpression and association with joint damage is characteristic of RA rather than PsA, and that p53 ST expression might be a prognostic marker of joint damage in RA.
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Figure 1.
Immunofluorescence (A) and immunohistochemical (B) staining for p53 in ST of the same patient with RA. Technique with tyramide enhancement (see text). Original magnification x600 (A and B).
Figure 2.
Immunostaining for p53 tissue in ST from patients with RA (A and B) and PsA (C and D). Original magnification x400 (A); x600 (B); x400 (C), and x1000 (D).
Selected References
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- Bruynesteyn K., van der Heijde D., Boers M., Lassere M., Boonen A., Edmonds J., Houben H., Paulus H., Peloso P., Saudan A. Minimal clinically important difference in radiological progression of joint damage over 1 year in rheumatoid arthritis: preliminary results of a validation study with clinical experts. J Rheumatol. 2001 Apr;28(4):904–910. [PubMed] [Google Scholar]
- Cañete Juan D., Pablos José L., Sanmartí Raimon, Mallofré Carmen, Marsal Sara, Maymó Joan, Gratacós Jordi, Mezquita Jovita, Mezquita Cristobal, Cid Maria C. Antiangiogenic effects of anti-tumor necrosis factor alpha therapy with infliximab in psoriatic arthritis. Arthritis Rheum. 2004 May;50(5):1636–1641. doi: 10.1002/art.20181. [DOI] [PubMed] [Google Scholar]
- Cañete Juan D., Rodríguez José R., Salvador Georgina, Gómez-Centeno Antonio, Muñoz-Gómez J., Sanmartí Raimón. Diagnostic usefulness of synovial vascular morphology in chronic arthritis. A systematic survey of 100 cases. Semin Arthritis Rheum. 2003 Jun;32(6):378–387. doi: 10.1053/sarh.2002.50004. [DOI] [PubMed] [Google Scholar]
- Chu C. Q., Field M., Feldmann M., Maini R. N. Localization of tumor necrosis factor alpha in synovial tissues and at the cartilage-pannus junction in patients with rheumatoid arthritis. Arthritis Rheum. 1991 Sep;34(9):1125–1132. doi: 10.1002/art.1780340908. [DOI] [PubMed] [Google Scholar]
- Danning C. L., Illei G. G., Hitchon C., Greer M. R., Boumpas D. T., McInnes I. B. Macrophage-derived cytokine and nuclear factor kappaB p65 expression in synovial membrane and skin of patients with psoriatic arthritis. Arthritis Rheum. 2000 Jun;43(6):1244–1256. doi: 10.1002/1529-0131(200006)43:6<1244::AID-ANR7>3.0.CO;2-2. [DOI] [PubMed] [Google Scholar]
- Fearon Ursula, Griosios Konstantina, Fraser Alexander, Reece Richard, Emery Paul, Jones Pamela F., Veale Douglas J. Angiopoietins, growth factors, and vascular morphology in early arthritis. J Rheumatol. 2003 Feb;30(2):260–268. [PubMed] [Google Scholar]
- Firestein G. S., Echeverri F., Yeo M., Zvaifler N. J., Green D. R. Somatic mutations in the p53 tumor suppressor gene in rheumatoid arthritis synovium. Proc Natl Acad Sci U S A. 1997 Sep 30;94(20):10895–10900. doi: 10.1073/pnas.94.20.10895. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Firestein G. S., Nguyen K., Aupperle K. R., Yeo M., Boyle D. L., Zvaifler N. J. Apoptosis in rheumatoid arthritis: p53 overexpression in rheumatoid arthritis synovium. Am J Pathol. 1996 Dec;149(6):2143–2151. [PMC free article] [PubMed] [Google Scholar]
- Gladman D. D., Stafford-Brady F., Chang C. H., Lewandowski K., Russell M. L. Longitudinal study of clinical and radiological progression in psoriatic arthritis. J Rheumatol. 1990 Jun;17(6):809–812. [PubMed] [Google Scholar]
- Gladman Dafna D. Current concepts in psoriatic arthritis. Curr Opin Rheumatol. 2002 Jul;14(4):361–366. doi: 10.1097/00002281-200207000-00005. [DOI] [PubMed] [Google Scholar]
- Hannuksela-Svahn A., Päkkö P., Autio P., Reunala T., Karvonen J., Vähäkangas K. Expression of p53 protein before and after PUVA treatment in psoriasis. Acta Derm Venereol. 1999 May;79(3):195–199. doi: 10.1080/000155599750010959. [DOI] [PubMed] [Google Scholar]
- Kane David, Jensen Liselotte E., Grehan Sharon, Whitehead Alexander S., Bresnihan Barry, Fitzgerald Oliver. Quantitation of metalloproteinase gene expression in rheumatoid and psoriatic arthritis synovial tissue distal and proximal to the cartilage-pannus junction. J Rheumatol. 2004 Jul;31(7):1274–1280. [PubMed] [Google Scholar]
- Kullmann F., Judex M., Neudecker I., Lechner S., Jüsten H. P., Green D. R., Wessinghage D., Firestein G. S., Gay S., Schölmerich J. Analysis of the p53 tumor suppressor gene in rheumatoid arthritis synovial fibroblasts. Arthritis Rheum. 1999 Aug;42(8):1594–1600. doi: 10.1002/1529-0131(199908)42:8<1594::AID-ANR5>3.0.CO;2-#. [DOI] [PubMed] [Google Scholar]
- Lee C. S., Portek I., Edmonds J., Kirkham B. Synovial membrane p53 protein immunoreactivity in rheumatoid arthritis patients. Ann Rheum Dis. 2000 Feb;59(2):143–145. doi: 10.1136/ard.59.2.143. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Maestro Miguel A., Boj Sylvia F., Luco Reini F., Pierreux Christophe E., Cabedo Judit, Servitja Joan M., German Michael S., Rousseau Guy G., Lemaigre Frederic P., Ferrer Jorge. Hnf6 and Tcf2 (MODY5) are linked in a gene network operating in a precursor cell domain of the embryonic pancreas. Hum Mol Genet. 2003 Oct 21;12(24):3307–3314. doi: 10.1093/hmg/ddg355. [DOI] [PubMed] [Google Scholar]
- McGonagle D., Conaghan P. G., Emery P. Psoriatic arthritis: a unified concept twenty years on. Arthritis Rheum. 1999 Jun;42(6):1080–1086. doi: 10.1002/1529-0131(199906)42:6<1080::AID-ANR2>3.0.CO;2-7. [DOI] [PubMed] [Google Scholar]
- Mulherin D., Fitzgerald O., Bresnihan B. Synovial tissue macrophage populations and articular damage in rheumatoid arthritis. Arthritis Rheum. 1996 Jan;39(1):115–124. doi: 10.1002/art.1780390116. [DOI] [PubMed] [Google Scholar]
- Pap T., Aupperle K. R., Gay S., Firestein G. S., Gay R. E. Invasiveness of synovial fibroblasts is regulated by p53 in the SCID mouse in vivo model of cartilage invasion. Arthritis Rheum. 2001 Mar;44(3):676–681. doi: 10.1002/1529-0131(200103)44:3<676::AID-ANR117>3.0.CO;2-6. [DOI] [PubMed] [Google Scholar]
- Reece R. J., Canete J. D., Parsons W. J., Emery P., Veale D. J. Distinct vascular patterns of early synovitis in psoriatic, reactive, and rheumatoid arthritis. Arthritis Rheum. 1999 Jul;42(7):1481–1484. doi: 10.1002/1529-0131(199907)42:7<1481::AID-ANR23>3.0.CO;2-E. [DOI] [PubMed] [Google Scholar]
- Ritchlin C., Haas-Smith S. A., Hicks D., Cappuccio J., Osterland C. K., Looney R. J. Patterns of cytokine production in psoriatic synovium. J Rheumatol. 1998 Aug;25(8):1544–1552. [PubMed] [Google Scholar]
- Ritchlin Christopher T., Haas-Smith Sally A., Li Ping, Hicks David G., Schwarz Edward M. Mechanisms of TNF-alpha- and RANKL-mediated osteoclastogenesis and bone resorption in psoriatic arthritis. J Clin Invest. 2003 Mar;111(6):821–831. doi: 10.1172/JCI16069. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sanmarti R., Gomez A., Ercilla G., Gratacos J., Larrosa M., Suris X., Vinas O., Salvador G., Munoz-Gomez J., Canete J. D. Radiological progression in early rheumatoid arthritis after DMARDS: a one-year follow-up study in a clinical setting. Rheumatology (Oxford) 2003 Apr 16;42(9):1044–1049. doi: 10.1093/rheumatology/keg284. [DOI] [PubMed] [Google Scholar]
- Seemayer C. A., Kuchen S., Neidhart M., Kuenzler P., Rihosková V., Neumann E., Pruschy M., Aicher W. K., Müller-Ladner U., Gay R. E. p53 in rheumatoid arthritis synovial fibroblasts at sites of invasion. Ann Rheum Dis. 2003 Dec;62(12):1139–1144. doi: 10.1136/ard.2003.007401. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sun Yubo, Cheung Herman S. p53, proto-oncogene and rheumatoid arthritis. Semin Arthritis Rheum. 2002 Apr;31(5):299–310. doi: 10.1053/sarh.2002.31550. [DOI] [PubMed] [Google Scholar]
- Tak P. P., Klapwijk M. S., Broersen S. F., van de Geest D. A., Overbeek M., Firestein G. S. Apoptosis and p53 expression in rat adjuvant arthritis. Arthritis Res. 2000 Mar 1;2(3):229–235. doi: 10.1186/ar92. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tak P. P., Smeets T. J., Boyle D. L., Kraan M. C., Shi Y., Zhuang S., Zvaifler N. J., Breedveld F. C., Firestein G. S. p53 overexpression in synovial tissue from patients with early and longstanding rheumatoid arthritis compared with patients with reactive arthritis and osteoarthritis. Arthritis Rheum. 1999 May;42(5):948–953. doi: 10.1002/1529-0131(199905)42:5<948::AID-ANR13>3.0.CO;2-L. [DOI] [PubMed] [Google Scholar]
- Tak P. P., Zvaifler N. J., Green D. R., Firestein G. S. Rheumatoid arthritis and p53: how oxidative stress might alter the course of inflammatory diseases. Immunol Today. 2000 Feb;21(2):78–82. doi: 10.1016/s0167-5699(99)01552-2. [DOI] [PubMed] [Google Scholar]
- Yamanishi Yuji, Boyle David L., Pinkoski Michael J., Mahboubi Artin, Lin Tesu, Han Zuoning, Zvaifler Nathan J., Green Douglas R., Firestein Gary S. Regulation of joint destruction and inflammation by p53 in collagen-induced arthritis. Am J Pathol. 2002 Jan;160(1):123–130. doi: 10.1016/S0002-9440(10)64356-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yamanishi Yuji, Boyle David L., Rosengren Sanna, Green Douglas R., Zvaifler Nathan J., Firestein Gary S. Regional analysis of p53 mutations in rheumatoid arthritis synovium. Proc Natl Acad Sci U S A. 2002 Jul 15;99(15):10025–10030. doi: 10.1073/pnas.152333199. [DOI] [PMC free article] [PubMed] [Google Scholar]