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1.
Etiopathogenesis of the rheumatoid arthritis-like disease in MRL/l mice. I. The histomorphologic basis of joint destruction 总被引:4,自引:0,他引:4
MRL/l mice spontaneously develop a hindlimb arthropathy, as well as a number of immunologic abnormalities, including circulating rheumatoid factors. Although previous studies have suggested that this arthropathy is primarily an inflammatory process, we performed a comprehensive histomorphologic study which indicated that inflammation is a late manifestation of MRL/l arthritis. The pathologic changes that occur in the joints of these mice can be divided into 3 stages. The first stage develops between the ages of 7 and 13 weeks and consists of synovial cell proliferation in the joint recesses. The second stage is characterized by continued proliferation of synovial cells which take on an appearance similar to that of transformed mesenchymal cells. The earliest destructive changes occur in the second stage and include marginal erosions, followed soon after by progressive destruction of articular and meniscal cartilage. The final stage is characterized by a diminution of synovial cel proliferation, extensive cartilage destruction, formation of scar tissue and fibrocartilage, and a very moderate infiltration of the synovial stroma by mononuclear and polymorphonuclear inflammatory cells. Throughout the disease progression there is a striking dissociation between inflammatory cell infiltration or exudation and tissue destruction. The histomorphologic similarities between human rheumatoid synovitis and the arthritis of MRL/l mice, as well as the presence of rheumatoid factors, make this mouse strain an excellent model for studying human rheumatoid arthritis. 相似文献
2.
Frank X. O'sullivan Hans-Georg Fassbender Steffen Gay William J. Koopman 《Arthritis \u0026amp; Rheumatology》1985,28(5):529-536
MRL/1 mice spontaneously develop a hindlimb arthropathy, as well as a number of immunologic abnormalities, including circulating rheumatoid factors. Although previous studies have suggested that this arthropathy is primarily an inflammatory process, we performed a comprehensive histomorphologic study which indicated that inflammation is a late manifestation of MRL/1 arthritis. The pathologic changes that occur in the joints of these mice can be divided into 3 stages. The first stage develops between the ages of 7 and 13 weeks and consists of synovial cell proliferation in the joint recesses. The second stage is characterized by continued proliferation of synovial cells which take on an appearance similar to that of transformed mesenchymal cells. The earliest destructive changes occur in the second stage and include marginal erosions, followed soon after by progressive destruction of articular and meniscal cartilage. The final stage is characterized by a diminution of synovial cell proliferation, extensive cartilage destruction, formation of scar tissue and fibrocartilage, and a very moderate infiltration of the synovial stroma by mononuclear and polymorphonuclear inflammatory cells. Throughout the disease progression there is a striking dissociation between inflammatory cell infiltration or exudation and tissue destruction. The histomorphologic similarities between human rheumatoid synovitis and the arthritis of MRL/1 mice, as well as the presence of rheumatoid factors, make this mouse strain an excellent model for studying human rheumatoid arthritis. 相似文献
3.
Tak PP 《Best Practice & Research: Clinical Rheumatology》2001,15(1):17-26
Thoughts on treatment for the early control of synovitis have stimulated research on pathobiological events at the site of inflammation in patients with early rheumatoid arthritis. Several studies have thus been conducted to examine synovial biopsy samples at various stages of the disease. The most important conclusion from these studies is that all features of chronic synovial inflammation can be observed in so-called early rheumatoid arthritis. This suggests that no arguments exist for the effect of therapeutic intervention on synovitis varying in different phases of rheumatoid arthritis. In end-stage rheumatoid arthritis, factors that are secondary to the disease may contribute to the perpetuation of synovial inflammation. Mutations in key regulatory genes could play a role in the autonomous progression of the disease. In addition, it is conceivable that the release of bone and cartilage fragments might elicit an inflammatory response in patients with destructive rheumatoid arthritis. 相似文献
4.
Update on synovitis 总被引:2,自引:0,他引:2
Rheumatoid arthritis (RA) is an inflammatory disorder associated with chronic synovitis, eventually leading to cartilage and
bone destruction in the joints. Synovitis is associated with the activation of various cells in the synovium including synovial
lining cells, interstitial macrophages, endothelial cells, lymphocytes, and fibroblasts. The key mechanisms underlying synovitis
include inflammatory cell adhesion and activation, the production of mediators (such as cytokines, chemokines, and growth
factors), angiogenesis, joint destruction, fibrosis, and bone resorption. These important events, as well as the role of inflammatory
cells, cell surface molecules, and soluble mediators are updated and discussed in this review. Some aspects and strategies
of current or future immunotherapy are also discussed because these animal and human trials provide information on the pathogenesis
of inflammatory synovitis. 相似文献
5.
Immune features of seronegative and seropositive arthritis in early synovitis studies 总被引:2,自引:0,他引:2
Synovitis of recent onset is a challenging problem, both from a diagnostic and a mechanistic point of view. The role of the immune system in mediating the systemic and synovial inflammatory response remains an area of active investigation. Studies in early synovitis cohorts have confirmed the relatively specific association of rheumatoid factor positive polyarthritis with a number of autoantibodies, particularly anticyclical citrullinated peptide (CCP) antibodies, antifilaggarin antibodies (AFA), and anti-Sa antibodies. Immunopathologic studies of synovial tissue samples from patients with early synovitis have generally suggested quantitative rather than qualitative differences between various forms of synovitis. In particular, Th1 cytokines appear to predominate in rheumatoid arthritis and psoriatic synovitis, while Th2 cytokines are more often detectable in the synovium of reactive arthritis patients. This latter observation is consistent with an immune response profile that favors persistence of intracellular organisms. 相似文献
6.
A complex of clinical radiation and MRI studies of the joint was conducted in 45 patients with tuberculous arthritis. Two major forms of tuberculous lesion of the joint were identified: primary osseous tuberculous arthritis (79.6%) and tuberculous allergic synovitis (20.4%). In patients with tuberculous allergic synovitis, MRI revealed a nonspecific exudative proliferative response of the synovial membrane and edema of the bone marrow and periarticular tissues. In primary osseous tuberculous arthritis, MRI showed tuberculous inflammation foci in the epiphysis of the bone; proliferative changes in the synovial membrane, destruction of cartilaginous, fibrous, and osseous structures, as well as periarticular abscesses. 相似文献
7.
Antifibrotic action of interleukin-1 receptor antagonist in lapine monoarticular arthritis.
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J Lewthwaite S Blake R C Thompson T E Hardingham B Henderson 《Annals of the rheumatic diseases》1995,54(7):591-596
OBJECTIVE--To determine if the administration of interleukin-1 receptor antagonist (IL-1ra) to animals with established antigen induced arthritis had any beneficial effects on the synovitis and cartilage destruction. METHODS--Antigen induced arthritis was induced in New Zealand White rabbits, and after two weeks IL-1ra was administered every six hours over a 72 hour period. Animals were then killed and joint tissues examined for the degree of synovitis, synovial fibrosis, and cartilage damage. RESULTS--The response of the arthritis to the treatment was minor in terms of joint swelling, leucocyte accumulation, or cartilage proteoglycan loss. However, the synovial fibrosis was not only halted by administration of IL-1ra, but reversed. The inflamed synovial linings of IL-1ra treated animals showed a significant loss of synovial collagen content and a reappearance of the synovial fat spaces which are prominent in the normal synovial lining. CONCLUSION--This study shows that IL-1ra has potent antifibrotic activity and suggests the use of this agent for the reversal of the fibroproliferative process which is so important in the pathology of rheumatoid arthritis. 相似文献
8.
《Best Practice & Research: Clinical Rheumatology》2014,28(4):565-576
Biological therapies for the management of immune mediated inflammatory diseases such as rheumatoid arthritis have proven to be extremely successful in recent years. Despite these successes, even the most effective of therapies do not lead to cure. Why chronic inflammation persists indefinitely within the rheumatoid synovium despite an absence of continuous stimulation, and why some patients with early synovitis progress to persistent disease whilst others do not, has remained unexplained. In contrast to the paradigm that stromal cells are biochemically active but immunologically passive, there is now growing evidence that stromal components from the rheumatoid synovium play a crucial part in the immunopathology of rheumatoid arthritis. Stromal cells play a central role in the transformation of an acute, resolving to a chronic inflammatory process, and to the persistence of synovial inflammation and joint destruction through a variety of immune mechanisms. Therapeutic manipulation of the stroma is a largely unexplored, yet potentially vital area of research. Targeting pathogenic stromal cells has the potential to provide a cure for chronic inflammatory disorders such as rheumatoid arthritis. 相似文献
9.
Choy E 《Current rheumatology reports》2008,10(5):413-417
Interleukin (IL)-6 is the most abundant proinflammatory cytokine in the circulation and synovial joints of patients with active
rheumatoid arthritis. It has pivotal roles in the immune response and inflammation. In rheumatoid arthritis, it causes synovitis,
joint destruction, and many systemic manifestations. Clinical trials of tocilizumab, a humanized anti-IL-6 receptor monoclonal
antibody that blocks IL-6 signaling, have demonstrated therapeutic benefit. It heralds a new era of anticytokine therapy in
rheumatoid arthritis. 相似文献
10.
OBJECTIVE. Tenascin is an extracellular matrix glycoprotein with effects on cell adhesion, cell migration, and lymphocyte activation. We proposed to identify the expression of human tenascin messenger RNA (mRNA) and protein in inflammatory synovitis and in normal synovium, and to identify potential regulatory cytokines. METHODS. Immunohistochemistry and in situ hybridization were used to identify the expression of tenascin in synovium. Northern blot analysis of RNA and both immunoblot analysis and enzyme-linked immunosorbent assay of proteins were used to identify tenascin in synovial cell cultures. RESULTS. Tenascin was found along the synovial lining layer and in perivascular areas of normal synovium. In inflammatory synovitis, tenascin protein and mRNA expression were shown to be increased in the synovial lining layer, in perivascular areas, in lymphoid aggregates, and in areas of fibrosis. Interleukin-1, a major mediator of tissue injury in inflammatory synovitis, induced tenascin expression and deposition in primary synovial fibroblast cultures. CONCLUSION. Tenascin mRNA and protein are increased in inflammatory synovitis, and interleukin-1 is an inducer of tenascin in synovial fibroblasts. This identifies a new pathway by which interleukin-1 alters the extracellular matrix composition in synovitis. Since tenascin has effects on lymphocyte activation and cell adhesion, the induction of tenascin in inflammatory synovitis may play a role in the pathophysiology of arthritis. 相似文献
11.
Angiogenesis inhibition, long studied in the treatment of malignancies, has begun to emerge as a potential therapeutic approach in managing inflammatory arthritis, particularly rheumatoid arthritis. The growth of new vessels is required for the development of the rheumatoid pannus, which then leads to extensive synovial inflammation and joint destruction. Vascular endothelial growth factor is the best studied mediator of angiogenesis, and several therapies have been developed that specifically target this molecule. Several other angiogenesis mediators, such as the angiopoietin-TIE system, hypoxia inducible factor and integrin alpha(V)beta(3), as well as naturally occurring inhibitors of angiogenesis, are also being investigated as potential therapeutic targets. Additionally, there are a number of drugs, including paclitaxel, 2-methoxyestradiol and fumagillin analogs, that might have a role in inhibiting angiogenesis and, thus, in treating proliferative synovitis. 相似文献
12.
Psoriatic arthritis (PsA) is a chronic inflammatory arthropathy associated with psoriasis that affects the peripheral joints,
spine, and entheses. Most patients with PsA present with peripheral synovitis of the oligoarticular or polyarticular subtype.
As one of the targets of this disease, studies on the synovium may provide insight into the mechanisms involved in this condition.
Key findings from the available studies comparing synovial tissue of PsA and rheumatoid arthritis patients are discussed in
this review. Also, changes in the synovial infiltrate, expression of proinflammatory cytokines and adhesion molecules, and
vascularity in synovial tissue after treatment with various medications are addressed. Finally, a model for proof-of-principle
study design using serial synovial biopsies is described, which could be used to predict clinical (in)efficacy in early clinical
trial design in PsA. 相似文献
13.
Arthritis associated with adjuvant mycobacterial treatment for carcinoma of the bladder. 总被引:3,自引:0,他引:3
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A patient who developed an inflammatory polyarthritis following intravesical administration of bacillus Calmette-Guérin (BCG) used in the treatment of bladder cancer is described. An inflammatory synovitis comprising predominantly T lymphocytes was demonstrated on synovial biopsy. The synovitis resolved spontaneously within 14 days in this 'human model' of adjuvant arthritis. 相似文献
14.
B. Taillan M.D. J. F. Leyge J. G. Fuzibet F. Nectoux G. Ziegler P. Dujardin 《Clinical rheumatology》1991,10(1):76-77
Summary We report one case of leukemic synovitis in a patient with a 40-year history of rheumatoid arthritis. The synovial fluid sample and synovial biopsy specimen showed myeloblastic cells. So, leukemic synovitis can be suspected in a patient with inflammatory rheumatism and adequate diagnostic procedures should be carried out. 相似文献
15.
Objective. Tenascin is an extracellular matrix glycoprotein with effects on cell adhesion, cell migration, and lymphocyte activation. We proposed to identify the expression of human tenascin messenger RNA (mRNA) and protein in inflammatory synovitis and in normal synovium, and to identify potential regulatory cytokines. Methods. Immunohistochemistry and in situ hybridization were used to identify the expression of tenascin in synovium. Northern blot analysis of RNA and both immunoblot analysis and enzyme-linked immunosorbent assay of proteins were used to identify tenascin in synovial cell cultures. Results. Tenascin was found along the synovial lining layer and in perivascular areas of normal synovium. In inflammatory synovitis, tenascin protein and mRNA expression were shown to be increased in the synovial lining layer, in perivascular areas, in lymphoid aggregates, and in areas of fibrosis. Interleukin-1, a major mediator of tissue injury in inflammatory synovitis, induced tenascin expression and deposition in primary synovial fibroblast cultures. Conclusion. Tenascin mRNA and protein are increased in inflammatory synovitis, and interleukin-1 is an inducer of tenascin in synovial fibroblasts. This identifies a new pathway by which interleukin-1 alters the extracellular matrix composition in synovitis. Since tenascin has effects on lymphocyte activation and cell adhesion, the induction of tenascin in inflammatory synovitis may play a role in the pathophysiology of arthritis. 相似文献
16.
Jakobs M Morawietz L Rothschenk H Hopf T Weiner S Schausten H Krukemeyer MG Krenn V 《Zeitschrift für Rheumatologie》2007,66(8):706-712
Histopathological assessment of synovial biopsies has an established value. The value for inflammatory joint diseases without standardized rating mechanisms was, however, unknown until recently. The exemplary use of the synovitis score in four cases all including recurrent bruises of the knee joint portrays its value for diagnosis and therapy.Usage of the score includes assessing the enlargement of the lining layer, cellular density of synovial stroma and leucocyte infiltration by giving each a score of 0-3 points and adding them. Presence of high-grade synovitis (>or=4 points) in all cases displayed the reason for the joint bruises within a primarily inflammatory, rheumatoid circle.In this report we show the broad variety of uses for the synovitis score dealing with cases of Lyme arthritis, rheumatoid arthritis, seronegative monarthritis and HLA-B27-positive peripheral arthritis. 相似文献
17.
Immunohistologic analysis of the distribution of cell adhesion molecules within the inflammatory synovial microenvironment 总被引:18,自引:0,他引:18
L P Hale M E Martin D E McCollum J A Nunley T A Springer K H Singer B F Haynes 《Arthritis and rheumatism》1989,32(1):22-30
Antigen-independent binding of T lymphocytes to a variety of cell types has been shown to be mediated by receptor-ligand pairs of adhesion molecules. In forms of inflammatory synovitis (including rheumatoid arthritis), T cells home to synovium, become activated, and participate in the generation of chronic synovitis. Using indirect immunofluorescence assays on synovial frozen tissue sections and on synovial fibroblast cell lines, we studied the distribution of cell adhesion molecules on components of the synovial microenvironment in inflammatory synovitis. We reasoned that analysis of the cell types within synovium that express adhesion molecules might provide clues to lymphocyte-stromal interactions that occur in inflammatory synovitis. We found that antibodies against the lymphocyte function-associated antigen 3 (LFA-3) molecule and the intercellular adhesion molecule 1 (ICAM-1) both reacted with macrophage-like type A synovial cells and synovial fibroblasts, as well as with tissue macrophages and vessel endothelium. Using flow cytometry, we found that anti-LFA-3 and anti-ICAM-1 (but not antibodies against their ligands CD2 and LFA-1) reacted with synovial fibroblast cells cultured in vitro. Thus, these data demonstrate that the ligands for lymphocyte LFA-1 molecules (ICAM-1) and for T cell CD2 molecules (LFA-3) are widely distributed among cell types of the synovial microenvironment and provide numerous cell types with which lymphocytes can interact via these 2 adhesion pathways during the course of inflammatory synovitis. 相似文献
18.
OBJECTIVE. Synovial fluid lymphocytes from patients with rheumatoid arthritis and with other forms of inflammatory synovitis demonstrate enhanced proliferative responses to Mycobacterium tuberculosis antigens, in particular, the 65-kd heat-shock protein. There is a high degree of homology between the human and the mycobacterial 60-kd family of heat-shock proteins. These studies were performed to determine if the enhanced response to the mycobacterial 65-kd heat-shock protein was due to cross-reactivity of an immune response generated against the human homolog. METHODS. These studies were performed by in vitro culture of isolated synovial fluid mononuclear cells with crude and purified antigens. RESULTS. The synovial fluid lymphocytes of a majority of patients with rheumatoid arthritis recognized the mycobacterial 65-kd heat-shock protein, as evidenced by T cell proliferation. In contrast, only 18% of all samples tested responded to a highly purified recombinant human 60-kd heat-shock protein. With only one exception, proliferative responses to the mycobacterial antigen were stronger than those to the human homolog. The proliferative responses generated against mycobacterial 65-kd heat-shock proteins from different sources were highly correlated. CONCLUSION. The findings suggest that the enhanced proliferative response to the mycobacterial 65-kd heat-shock protein noted in most patients with rheumatoid arthritis and other forms of inflammatory synovitis is not due to cross-reactivity of an immune response directed against the human heat-shock protein. 相似文献
19.
A. König V. Krenn R. Gillitzer J. Glöckner E. Janßen F. Gohlke J. Eulert H. K. Müller-Hermelink 《Rheumatology international》1997,17(4):159-168
Psoriatic arthritis is an inflammatory arthropathy that ultimately can lead to joint destruction. In this study, we investigated
the immunophenotype of the inflammatory cells and the expression of interleukin-8 (IL-8), which is the hallmark chemoattractant
cytokine of psoriasis in synovial membranes from patients exhibiting active psoriatic synovitis (n=9). The tissue samples were examined by immunohistochemistry, Western blot analysis and in situ hybridisation. The inflammatory
infiltrate consisted predominantly of CD3+ T lymphocytes, with a higher proportion of CD4+ than CD8+ T lymphocytes in six cases. CD3+ T lymphocytes were focally distributed near small blood vessels and the enlarged synovial intima. CD1+ interdigitating reticulum cells were not detected. CD22+ B lymphocytes and plasma cells were found in small aggregates without KiM4+ follicular dendritic cells. KiM8+ macrophages were located in the synovial intima and were distributed in a diffuse pattern near the synovial lining cells.
CD15+ neutrophil granulocytes were detected in four cases. They were preferentially located in the vicinity of blood vessels and
the synovial intima. IL-8 was found at a high level in the synovial lining cells and to a lesser extent in cells located in
the perivascular areas. Immunofluorescence double staining showed IL-8 to be expressed in KiM8+ multinucleated giant cells, KiM8+ macrophages and CD3+ T lymphocytes. IL-8 receptor A was demonstrated in the synovial lining and in macrophages and lymphocytes. IL-8 was detected
by immunoblot analysis of the synovial tissue at 8.4 kD. Employing in situ hybridisation, IL-8 mRNA was strongly and preferentially
expressed in the synovial intima, as well as in macrophages and lymphocytes. The immunophenotype of the psoriatic arthritis
inflammatory cells shows great similarity to the inflammatory infiltrate found in the synovial tissue of patients with rheumatoid
arthritis. The preferential expression of IL-8 and IL-8 mRNA in the enlarged synovial intima and in lymphocytes and macrophages
suggests that IL-8 exerts its action through activated mononuclear cells and T lymphocytes. It seems to play a role in regulating
leucocyte traffic into the enlarged synovial intima and may contribute to the aggressive synovitis of patients with psoriatic
arthritis.
Received: 14 August 1997 / Accepted: 25 August 1997 相似文献
20.
Daniel Cejka Silvia Hayer Birgit Niederreiter Wolfgang Sieghart Thorsten Fuereder Jochen Zwerina Georg Schett 《Arthritis \u0026amp; Rheumatology》2010,62(8):2294-2302