Signaling and effector pathways

Current Opinion in Rheumatology

Volumn 11, Issue 3, 1999, Pages 194-201

  Müller Ladner, Ulf ^a,b   Gay, Renate E ^b   Gay, Steffen ^b  

^a UNIVERSITY OF REGENSBURG   (Germany)

^b UNIVERSITY HOSPITAL ZURICH   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

JOINT DESTRUCTION; PATHOPHYSIOLOGY; PRIORITY JOURNAL; REVIEW; RHEUMATOID ARTHRITIS; SYNOVIUM;

ARTHRITIS, RHEUMATOID; CELL ADHESION; CELL COMMUNICATION; HUMANS; SIGNAL TRANSDUCTION; SYNOVIAL MEMBRANE;

EID: 0345085507     PISSN: 10408711     EISSN: None     Source Type: Journal    
DOI: 10.1097/00002281-199905000-00008     Document Type: Review

References (97)

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2. 2 Klimiuk PA, Goronzy JJ, Bǰornsson J, Beckenbaugh RD, Weyand CM: Tissue cytokine patterns distinguish variants of rheumatoid synovitis. Am J Pathol 1997, 151:1311-1319.
3. 3 Alonzi T, Fattori E, Lazzaro D, Costa P, Probert L, Kollias G, et al.: Interleukin 6 is required for the development of collagen-induced arthritis. J Exp Med 1998, 4:461-468.
4. 4 Hermann JA, Hall MA, Maini RN, Feldmann M, Brennan FM: Important immunoregulatory role of interieukin-11 in the inflammatory process in rheumatoid arthritis. Arthritis Rheum 1998, 41:1388-1397.
5. 5 Müller-Ladner U, Roberts CR, Franklin BN, Gay RE, Robbins PD, Evans C, Gay S: Human IL-1 Ra gene transfer into human synovial fibroblasts is chondroprotective. J Immunol 1997, 158:3492-3498.
6. 6 Ma Y, Thornton S, Boivin GP, Hirsh D, Hirsch R, Hirsch E: Altered susceptibility to collagen-induced arthritis in transgenic mice with aberrant expression of interleukin-1 receptor antagonist. Arthritis Rheum 1998, 41:1798-1805.
7. 7 Van Meurs JBJ, van Lent PLEM, Singer II, Bayne EK, van de Loo FAJ, van den Berg WB: Interleukin-1 receptor antagonist prevents expression of the metalloproteinase-generated neoepitope VDIPEN in antigen-induced arthritis. Arthritis Rheum 1998, 41:647-656.
8. 8 Funk JL, Cordaro LA, Wei H, Benjamin JB, Yocum DE: Synovium as a source of increased amino-terminal parathyroid hormone-related protein expression in rheumatoid arthritis. J Clin Invest 1998, 101:1362-1371.
9. 9 Fowler MJ Jr, Neff MS, Borghaei RC, Pease EA, Mochan E, Thornton RD: Induction of bone morphogenetic protein-2 by interleukin-1 in human fibroblasts. Biochem Biophys Res Commun 1998, 248:450-453.
10. 10 Mattey DL, Dawes PT, Nixon NB, Slater H: Transforming growth factor β1 and interleukin 4 induced α smooth muscle actin expression and myofibroblast-like differentiation in human synovial fibroblasts in vitro: modulation by basic fibrofalast growth factor. Ann Rheum Dis 1997, 56:426-431.
11. 11 Langdon C, Leith J, Smith F, Richards CD: Oncostatin M stimulates monocyte chemoattractant protein-1-and interleukin-1-induced matrix metalloproteinase-1 production by human synovial fibroblasts in vitro. Arthritis Rheum 1997, 40:2139-2136.
12. 12 Cawston TE, Curry VA, Summers CA, Clark IM, Riley GP, Life PF, et al.: The role of oncostatin M in animal and human connective tissue collagen turnover and its localization within the rheumatoid joint. Arthritis Rheum 1998, 41:1760-1771.
13. The authors present interesting data on the regulation of the interleukin-6-like molecule oncostatin M and its effect on matrix metalloproteinase production.
14. 13 Barnes DA, Tse J, Kaufhold M, Owen M, Hesselgesser J, Strieter R, et al.: Polyclonal antibody directed against human RANTES ameliorates disease in the Lewis rat adjuvant-induced arthritis model. J Clin Invest 1998, 101:2910-2919.
15. 14 Volin MV, Shah MR, Tokuhira M, Haines GK III, Woods JM, Koch AE: RANTES expression and contribution to monocyte chemotaxis in arthritis. Clin Immunol Immunopathol 1998, 89:44-53.
16. 15 Leech M, Metz C, Santos L, Peng T, Holdsworth SR, Bucala R, Morand EF: Involvement macrophage migration inhibitory factor in the evolution of rat adjuvant arthritis. Arthritis Rheum 1998, 41:910-917.
17. 16 Recklies AD, Baillargeon L, White C: Regulation of cartilage oligomeric matrix protein synthesis in human synovial cells and articular chondrocytes. Arthritis Rheum 1998, 41:997-1006.
18. 17 Hummel KM, Neidhart M, Vilim V, Hauser N, Aicher WK, Gay RE, et al.: Analysis of cartilage oligomeric matrix protein (COMP) in synovial fibroblasts and synovial fluids. Br J Rheumatol 1998, 37:721-728.
19. 18 Glansbeek HL, van Beuningen HM, Vitters EL, van der Kraan PM, van den Berg WB: Stimulation of articular cartilage repair in established arthritis by local administration of transforming growth factor-beta into murine knee joints. Lab Invest 1998, 78:133-142.
20. 19 Sarkissian M, Lafyatis R: Transforming growth factor-β and platelet-derived growth factor regulation of fibrillar fibronectin matrix formation by synovila fibroblasts. J Rheumatol 1998, 25:613-622.
21. 20 Sánchez-Pernaute O, López-Armada MJ, Hernández P, Palacios I, Navarro F, Martinez J, et al.: Antifibroproliferative effect of tenidap in chronic antigen-induced arthritis. Arthritis Rheum 1997, 40:2147-2156.
22. 21 Paleolog EM, Young S, Stark AC, McCloskey RV, Feldmann M, Maini RN: Modulation of angiogentc vascular endothelial growth factor by tumor necrosis factor α and interleukin-1 in rheumatoid arthritis. Arthritis Rheum 1998, 41:1258-1265.
23. Important contribution in the field of neoangiogenesis in rheumatoid synovium underlining the effect of proinflammatory cytokines on angiogenic growth factors.
24. 22 Loredo GA, Benton HP: ATP and UTP activate calcium-mobilizing P2U-like receptors and act synergistically with interleukin-1 to stimulate prostaglandin E2 release from human rheumatoid synovial cells. Arthritis Rheum 1998, 41:246-255.
25. The authors present a novel mechanism of regulation of prostaglandin synthesis triggered by nucleotide-associated receptors and augmented by interleukin-1.
26. 23 Chen V, Croft D, Purkis P, Kramer IM: Co-culture of synovial fibroblasts and differentiated U937 cells is sufficient for high interleukin-6 but not interleukin-1β or tumour necrosis factor-alpha release. Br J Rheumatol 1998, 37:148-156.
27. 24 Sekine C, Yagita H, Miyasaka N, Okumura K: Expression and function of CD40 in rheumatoid synovium. J Rheumatol 1998, 25:1048-1053.
28. Interesting report on the potential proinflammatory role of CD40-CD40 ligand binding resulting in TNF-α. synthesis.
29. 25 Kiener HP, Baghestanian M, Dominkus M, Walschshofer S, Ghannadan M, Willheim M, et al.: Expression of the C5a receptor (CD88) on synovial mast cells of patients with rheumatoid arthritis. Arthritis Rheum 1998, 41:233-245.
30. 26 Rinaldi N, Barth TFE, Weis D, Schwarz-Eywill M, Pezzutto A, Lukoschek M, et al.: Loss of laminin and of the laminin receptor integrin subunit α6 in situ correlates with cytokine induced down regulation of α6 on fibroblast-like synoviocytes from rheumatoid arthritis. Ann Rheum Dis 1998, 57:559-565.
31. 27 Burger D, Rezzonico R, Li J-M, Modoux C, Pierce RA, Welgus HG, Dayer J-M: Imbalance between interstitial collagenase and tissue inhibitor of metalloproteinases 1 in synoviocytes and fibroblasts upon direct contact with stimulated T lymphocytes: involvement of membrane-associated cytokines. Arthritis Rheum 1998, 41:1748-1759.
32. Excellent presentation showing the impact of direct fibroblast-T cell interaction on collagenase production as well as insufficient collagenase inhibition by short-term upregulation of TIMP.
33. 28 Shang X-Z, Lang BJ, Issekutz AC: Adhesion molecule mechanisms mediating monocyte migration through synovial fibroblast and endothelium barriers: role for CD11/CD18, very late antigen-4 (CD49d/CD29), very late antigen-5 (CD49e/CD29), and vascular cell adhesion molecule-1 (CD106). J Immunol 1998, 160:467-474.
34. 29 Müller-Ladner U, Elices MJ, Kriegsmann JB, Strahl D, Gay RE, Firestein G, Gay S: Alternatively spliced CS-1 fibronectin isoform and its receptor VLA-4 in rheumatoid arthritis synovium. J Rheumatol 1997, 24:1873-1880.
35. 30 González-Alvaro I, Muñoz C, García-Vicũa R, Sabando P, Cabañas C, Sánchez-Madrid F, Diaz-González F: Interference of nonsteroidal drugs with very late activation antigen 4/vascular cell adhesion molecule-1-mediated lymphocyte-endothelial cell adhesion. Arthritis Rheum 1998, 41:1677-1688.
36. Reveals one of the potential pathways affected by nonsteroidal anti-inflammatory drugs, which decreased VCAM/VLA adhesion molecule interaction of peripheral blood lymphocytes.
37. 31 Sakai K, Matsuno H, Tsuji H, Tohyama M: Substance P receptor (NK1) gene expression in synovial tissue in rheumatoid arthritis and osteoarthritis. Scand J Rheumatol 1998, 27:135-141.
38. 32 Lambert N, Lescoulié PL, Yassine-Diab B, Enault G, Mazières B, De Préval C: Substance P enhances cytokine-induced vascular cell adhesion molecule-1 (VCAM-1) expression on cultured rheumatoid fibroblast-like synoviocytes. Clin Exp Immunol 1998, 113:269-275.
39. 33 Wahl C, Liptay S, Adler G, Schmid RM: Sulfasalazine: a potent and specific inhibitor of NFΚB. J Clin Invest 1998, 101:1163-1174.
40. 34 Grimbacher B, Aicher WK, Peter HH, Eibel H: TNF-α induces the transcription factor Egr-1, pro-inflammatory cytokines and cell proliferation in human skin fibroblasts and synovial lining cells. Rheumatol Int 1998, 17:185-192.
41. 35 Gerritsen ME, Shen C-P, Perry A: Synovial fibroblasts and the sphingomyelinase pathway: sphingomyelin turnover and ceramide generation are not signaling mechanisms for the actions of tumor necrosis factor-α. Am J Pathol 1998, 152:505-512.
42. Convincing data on the role of TNF-α in regulation of gene transcription molecules such as NFΚB and induction of the stress kinase pathway.
43. 36 Schett G, Redlich K, Xu Q, Bizan P, Gröger M, Tohidast-Akrad M, et al.: Enhanced expression of heat shock protein (hsp 70) and heat shock factor 1 (HSF 1) activation in rheumatoid arthritis synovial tissue. J Clin Invest 1998, 102:302-311.
44. Demonstration of the influence of numerous proinflammatory cytokines on heat-shock related pathways, including heat-shock transcription factor-1.
45. 37 Wakisaka S, Suzuki N, Takeno M, Takeba Y, Nagafuchi H, Saito N, et al.: Involvement of simultaneous multiple transcription factor expression, including cAMP responsive element binding protein and OCT-1, for synovial cell outgrowth in patients with rheumatoid arthritis. Ann Rheum Dis 1998, 57:487-494.
46. The authors present interesting data addressing the presence of different nuclear transcription factors in rheumatoid synovial fibroblasts and the stimulatory role of interieukin-1.
47. 38 Miyazawa K, Mori A, Yamamoto K, Okudaira H: Constitutive transcription of the human interleukin-6 gene by rheumatoid synoviocytes: spontaneous activation of NF-ΚB and CBF-1. Am J Pathol 1998, 152:793-803.
48. 39 Miyazawa K, Mori A, Yamamoto K, Okudaira H: Transcriptional roles of CCAAT/enhancer binding protein-β nuclear factor-ΚB, and C-promoter binding factor 1 in interleukin (IL)-1β-induced IL-6 synthesis by human rheumatoid fibroblast-like synoviocytes. J Biol Chem 1998, 273:7620-7627.
49. A most interesting set of experiments outlining the relationship between proinflammatory cytokines such as II-6 and the binding activity of nuclear transcription factors in rheumatoid synovial fibroblasts.
50. 40 Borghaei RC, Rawlings PL Jr, Mochan E: Interleukin-4 suppression of interleukin-1-induced transcription of collagenase (MMP-1) and stromelysin 1 (MMP-3) in human synovial fibroblasts. Arthritis Rheum 1998, 41:1398-1406.
51. Although interleukin-4 is thought to be one of the rather less important cytokines in RA pathophysiology, its effects on matrix metalloproteinase synthesis are quite impressive.
52. 41 Schroen DJ, Chen JD, Vincenti MP, Brinckerhoff CH: The nuclear receptor corepressor SMRT inhibits interstitial collagenase (MMP-1) transcription through an HRE-independent mechanism. Biochem Biophys Res Commun 1997, 237:52-58.
53. 42 Miyazawa K, Mori A, Miyata H, Akahane M, Ajisawa Y, Okudaira H: Regulation of interleukin-1β-induced interleukin-6 gene expression in human flbroblast-like synoviocytes by p38 mitogen-activated protein kinase. J Biol Chem 1998, 273:24832-24838.
54. One of the most important publications within the review period, presenting a subcellular molecular mechanism of MAP kinase-dependent interleukin-6 mRNA stabilization in synovial fibroblasts.
55. 43 Coakley G, Mok CC, Hajeer AH, Ollier WER, Turner D, Sinnott PJ, et al.: Interleukin-10 promoter polymorphisms in rheumatoid arthritis and Felty's syndrome. Br J Rheumatol 1998, 37:988-991.
56. 44 Hajeer AH, Lazarus M, Turner D, Mageed RA, Vencowsky J, Sinnott P, et al.: IL-10 gene promoter polymorphisms in rheumatoid arthritis. Scand J Rheumatol 1998, 27:142-145.
57. 45 Mousavi-Jazi M, Bostrǒm L, Lǒvmark C, Linde A, Brytting M, Sundqvist V-A: Infrequent detection of cytomegalovirus and Epstein-barr virus DNA in synovial memebrane of patients with rheumatoid arthritis. J Rheumatol 1998, 25:623-628.
58. 46 Takahashi Y, Murai C, Shibata S, Munakata Y, Ishii T, Ishii K, et al.: Human parvovirus B19 as a causative agent for rheumatoid arthritis. Proc Natl Acad Sci U S A 1998, 95:8227-8232.
59. 47 Grimbacher B, Aicher WK, Peter HH, Eibel H: Measurement of transcription factor c-fos and EGR-1 mRNA transcription levels in synovial tissue by quantitative RT-PCR. Rheumatol Int 1997, 17: 109-112.
60. 48 Morita Y, Kashihara N, Yamamura M, Okamoto H, Harada S, Kawashima M, Makino H: Antisense oligonucleotides targeting c-fos mRNA inhibit rheumatoid synovial fibroblast proliferation. Ann Rheum Dis 1998, 57:122-124.
61. 49 Wakisaka S, Suzuki N, Saito N, Ochi T, Sakane T: Possible correction of abnormal rheumatoid arthritis synovial cell function by jun D transfection in vivo. Arthritis Rheum 1998, 41:470-481.
62. Inhibition of proliferate pathways bears the potential of future therapeutic approaches, and the results of the authors contribute to the achievement of this goal.
63. 50 Aupperle KR, Boyle DL, Hendrix M, Seftor EA, Zvaifler NJ, Barbosa M, Firestein GS: Regulation of synoviocyte proliferation, apoptosis, and invasion by the p53 tumor suppressor gene. Am J Pathol 1998, 152:1091-1098.
64. The authors present an intriguing concept of continuous inflammation resulting in mutation accumulation in RA synovium.
65. 51 Lewis EJ, Bishop J, Bottomley KMK, Bradshaw D, Brewster M, Broadhurts MJ, et al.: Ro 32-3555, an orally active collagenase inhibitor, prevents cartilage breakdown in vitro and in vivo. Br J Pharmacol 1997, 121:540-546.
66. 52 Tetlow LC, Woolley DE: Comparative immunolocalization studies of collagenase 1 and collagenase 3 production in the rheumatoid lesion, and by human chondrocytes and synoviocytes in vitro. Br J Rheumatol 1998, 37:64-70.
67. 53 Hanemaaijer R, Sorsa T, Konttinen YT, Ding Y, Sutinen M, Visser H, et al.: Matrix metalloproteinase-8 is expressed in rheumatoid synovial fibroblasts and endothelial cells: regulation by tumor necrosis factor-α and doxycycline. J Biol Chem 1997, 272:31504-31509.
68. 54 Mudgett JS, Hutchinson NI, Chartrain NA, Forsyth AJ, McDonnell J, Singer II, et al.: Susceptibility of stromelysin 1-deficient mice to collagen-induced arthritis and cartilage destruction. Arthritis Rheum 1998, 41:110-121.
69. Outstanding study showing that deletion of a gene encoding a matrix metalloproteinase definitively involved in joint destruction does not necessarily result in reduction of joint destruction, which underlines the complexity of RA pathophysiology.
70. 55 Keyszer G, Redlich A, Häupl T, Zacher J, Sparmann M, Ungethüm U, et al.: Differential expression of cathepsins B and L compared with matrix metalloproteinases and their respective inhibitors in rheumatoid arthritis and osteoarthritis: a parallel investigation by semiquantitative reverse transcriptase-polymerase chain reaction and immunohistochemistry. Arthritis Rheum 1998, 41:1378-1387.
71. 56 Matucci Cerinic M, Generini S, Partsch G, Pignone A, Dini G, Konttinen YJ, Del Rosso M: Synoviocytes from osteoarthritis and rheumatoid arthritis produce plasminogen activators and plasminogen activator inhibitor-1 and display u-PA receptors on their surface. Life Sci 1998, 63:441-453.
72. Nice study on the potential role of a destructive pathway, which should be studied more intensively.
73. 57 Migita K, Kawabe Y, Tominaga M, Origuchi T, Aoyagi T, Eguchi K: Serum amyloid A protein induces production of matrix metalloproteinases by human synovial fibroblasts. Lab Invest 1998, 78:535-539.
74. 58 Hummel KM, Petrow PK, Franz JK, Müller-Ladner U, Aicher WK, Gay RE, et al.: Cysteine proteinase Cathepsin K mRNA is expressed in synovium of patients with rheumatoid arthritis and is detected at sites of synovial bone destruction. J Rheumatol 1998, 25:1887-1894.
75. Interesting presentation showing the presence and distribution of a novel cathepsin, which appears to be specifically involved in joint destruction at the sites of invasion.
76. 59 Pap T, Pap G, Sainsbury I, Franz JK, Hummel KM, Gay RE, et al.: In-situ expression of membrane type-matrix metalloproteinase 1 (MT1-MMP) in fibroblasts and osteoclasts at the bone-implant interface of aseptically loosened joint arthroplastles. Arthritis Rheum 1998, 41:S362.
77. 60 Takayanagi H, Oda H, Yamamoto S, Kawaguchi H, Tanaka S, Nisnikawa T, Koshihara Y: A new mechanism of bone destruction in rheumatoid arthritis: synovial fibroblasts induce osteoclastogenesis. Biochem Biophys Res Commun 1997, 240:279-286.
78. Fascinating data on the capabilities of synovial fibroblasts in stimulating the differentiation of macrophages into bone-degrading multinucleated cells.
79. + T lymphocytes in rheumatoid arthritis. Eur J Immunol 1998, 28:2661-2671.
80. Outstanding paper demonstrating the potential of synovial fibroblasts to chemoattract inflammatory cells into the synovium by synthesis and release of interleukin-16.
81. 62 McInnes IB, al-Mughales J, Field M, Leung BP, Huang FP, Dixon R, et al.: The role of interleukin-15 in T-cell migration and activation in rheumatoid arthritis. Nat Med 1996, 3:189-195.
82. 63 Chabaud M, Fossiez F, Taupin J-L, Miossec P: Enhancing effect of IL-17 on IL-1-induced IL-6 and leukemia inhibitory factor production by rheumatoid arthritis synoviocytes and its regulation by Th2 cytokines. J Immunol 1998, 161:409-414.
83. 64 Garred P, Madsen HO, Petersen J, Marquardt H, Haansen TM, Sørensen SR, et al.: CC chemokine receptor 5 polymorphism in rheumatoid arthritis. J Rheumatol 1998, 25:1462-1465. Interesting paper illustrating the potential of chemokine blockade for RA therapy.
84. 65 Gay S, Kalden JR: Retroviruses and autoimmune rheumatic diseases. Clin Exp Immunol 994, 98:1-5.
85. 66 Aono H, Fujisawa K, Hsunuma T, Marriott SJ, Nishioka K: Extracellular human T cell leukemia virus type I tax protein stimulates the proliferation of human synovial cells. Arthritis Rheum 1998, 41:1995-2003. Very important report, which demonstrates for the first time that a retrovirus-related protein, and not bacterial antigens, is able to induce growth factors and proliferation in rheumatoid synovial fibroblasts.
86. 67 Imamura F, Aono H, Hasunuma T, Sumida T, Tateishi H, Maruo S, Nishioka K: Monoclonal expansion of synoviocytes in rheumatoid arthritis. Arthritis Rheum 1998, 41:1979-1986.
87. 68 Ermis A, Müller B, Hopf T, Hopf C, Remberger K, Jüsten HP, et al.: Invasion of human cartilage by cultured multicellular spheroids of rheumatoid synovial cells: a novel in vitro model system for rheumatoid arthritis. J Rheumatol 1998, 25:208-213.
88. 69 Van Lent PLEM, Holthuysen AEM, van Rooijen N, van de Loo FAJ, van de Putte LBA, van den Berg WB: Phagocytic synovial lining cells regulate acute and chronic joint inflammation after antigenic exacerbation of smouldering experimental murine arthritis. J Rheumatol 1998, 25:1135-1145.
89. 70 Van Lent PLEM, Holthuysen AEM, van Rooijen N, van de Putte LBA, van den Berg WB: Local removal of phagocytic synovial lining cells by clodronate-liposomes decreases cartilage destruction during collagen type II arthritis. Ann Rheum Dis 1998, 57:408-413. First report on the successful use of liposome-based delivery of inhibitory molecules in collagen-induced arthritis.
90. 71 Müller-Ladner U, Roberts CR, Franklin BN, Gay RE, Robbins PD, Evans C, Gay S: Human IL-1Ra gene transfer into human synovial fibroblasts is chondroprotective. J Immunol 1997, 158:3492-3498.
91. 72 Judex M, Müller-Ladner U, Jüsten H-P, Ballhorn W, Schǒlmerich J, Welsh J, et al.: RNA fingerprint-based detection of differentially regulated genes in different joints of a patient with rheumatoid arthritis. Arthritis Rheum 1998, 41:S319.
92. 73 Seki T, Selby J, Häupl T, Winchester R: Use of a differential subtraction method to identify genes that characterize the phenotype of cultured rheumatoid arthritis synoviocytes. Arthritis Rheum 1998, 41:1356-1364. Convincing experiments showing the impact of modern molecular biotechnology on the advance in knowledge in RA pathophysiology.
93. 74 Ma Y, Thornton S, Duwel LE, Boivin GP, Giannini EH, Leiden JM, et al.: Inhibition of collagen-induced arthritis by viral IL-10 gene transfer. J Immunol 1998, 161:1516-1524. This most fascinating study shows the importance of interleukin-10 as a key molecule in future novel therapeutic approaches for RA.
94. 75 Nguyen KHY, Boyle DL, McCormack JE, Chada S, Jolly DJ, Firestein GS: Direct synovial gene transfer with retroviral vectors in rat adjuvant arthritis. J Rheumatol 1998, 25:1118-1125.
95. 76 Foxwell B, Browne K, Bondeson J, Clarke C, de Martin R, Brennan F, Feldmann M: Efficient adenoviral infection with IΚBα reveals that macrophage tumor necrosis factor-α production in rheumatoid arthritis is NF-ΚB dependent. Proc Natl Acad Sci U S A 1998, 95:8211-8215.
96. 77 Evans CH, Whalen JD, Ghivizzani SC, Robbins PD: Gene therapy in autoimmune disease. Ann Rheum Dis 1998, 57:127-127. Excellent overview addressing numerous aspects of gene therapy in autoimmune diseases written by experts in the field.
97. 78 Jorgensen C, Gay S: Gene therapy in osteoarticular diseases: where are we? Immunol Today 1998, 9:387-391. This outstanding review not only reports the current knowledge on gene therapy in osteoarticular diseases but also presents numerous stimulating ideas for future projects in this area of rheumatology research.