Aging of the human synovium: an in vivo and ex vivo morphological study.

Age-associated changes of the human synovium have been investigated by microarthroscopy, optical and electron microscopy, immunohistochemistry, and cytochemistry. The knee joints of nineteen 15- to 56-year-old subjects, classified as normal by inspection, were carefully examined by microarthroscopy; small synovial tissue biopsy specimens from both the suprapatellar pouch and the medial tibiofemoral gutter were taken. Microarthroscopy showed that the villi were more numerous and the vascular network and cell distribution and profiles less regular in aged individuals. These data were confirmed by scanning electron microscopy, which also showed large areas of the synovial surface devoid of cells and collagen bundles in contact with the joint cavity in aged subjects. Light and transmission electron microscopy confirmed these data and allowed evaluation of the number, distribution, shape, and internal organization of cells as well as the distribution of vessels and the organization of the extracellular matrix in the full thickness of the synovium (down to 2 mm). Particular attention was paid to synovial lining cells, among which three main phenotypes could be recognized: synthetic type (present at all ages and hypertrophied in aged subjects), macrophagelike (increasing with age), and fibroblastlike. Collagen increased with age. Further studies are needed for comprehensive understanding of age-associated changes in the human synovium.

[Long term study on the efficacy and safety of lornoxicam in rheumatoid arthritis]. / Studio a lungo termine su efficacia e sicurezza terapeutica di lornoxicam nell'artrite reumatoide.

BACKGROUND: To assess the long term safety and therapeutic action of lornoxicam, a new non steroidal anti-inflammatory agent, in rheumatoid arthritis. METHODS: Open trial was carried out on different dosage schedules of lornoxicam (4 or 8 mg bid and 4mg tid) administered for six to twelve months. Patients of both sexes were enrolled, with classical or definite rheumatoid arthritis according to the A.R.A. criteria. RESULTS: Thirty-four patients (28 F, 6 M) were admitted, mean age (+/- SD) 53.9+/-14.2 years, mean duration of illness 9.2+/-10.7 years. Lornoxicam 8-16 mg/day showed good safety and therapeutic activity in long term treatment. Clinical improvement was limited, but progression of the disease was controlled. No adverse events were complained. CONCLUSIONS: Lornoxicam presented a worth-while therapeutic action and a good tolerability in rheumatoid arthritis long term treatment.

Microarthroscopic study of the morphologic features of normal and pathological synovial membrane.

The complex symptoms occurring in several internal knee diseases are usually related to changes in the synovial membrane, causing diagnostic and therapeutic problems. The conventional arthroscope, useful in establishing the diagnosis of internal derangement, is of questionable value in the differential diagnosis and evaluation of the stages of arthritis. With magnifying arthroscopy, it is possible to better show various forms of synovitis. Between 1983 and 1989, 3,000 knee joints were studied with conventional arthroscopy. In 400 of these joints, magnifying arthroscopic examination (microarthroscopy) was performed: 34 were normal, 57 had meniscal and ligamentous lesions, 220 had osteoarthritis, and 89 had inflammatory synovitis. We used two types of arthroscopes, Hamou-Storz and Microview-Wolf, adapted from a microhysteroscope, which provided a x 150 magnification of the conventional field. Referring to established microarthroscopic aspects of the synovial membrane in normal and pathological conditions, we have suggested microarthroscopic criteria for the differential diagnosis of synovitis in various pathological disorders. We believe that there are new applications for microarthroscopy because the instruments appear to have great potential value for both research and diagnosis.

T cell receptor beta chain gene usage in rheumatoid arthritis.

We evaluated the T cell receptor (TCR) V beta chain family expression in the peripheral blood lymphocytes from patients with rheumatoid arthritis, psoriatic arthritis and post traumatic synovitis. We used commercially available monoclonal antibodies and flow cytometry. No significant changes were observed in the percentages of the various TCR families when patients were compared to normal control. We also evaluated TCR families in paired samples from peripheral blood and synovial fluid of 6 patients. No synovial specific changes were documented. We conclude that by means of the available monoclonal antibodies, no mono, oligo-clonal T cell expansion can be detected in rheumatoid arthritis.

Circulating tumor necrosis factor alpha in rheumatoid arthritis.

Tumor Necrosis Factor alpha is an important mediator of immunity and inflammation, and because of its biologic activities (activation of neutrophils, release of arachidonic acid metabolites from synovial cells, induction of cartilage resorption and inhibition of proteoglycan release in cartilage) is one of the potential mediators of the chronic inflammation in rheumatoid arthritis. A commercially available ELISA was used to evaluate serum levels of Tumor Necrosis Factor alpha (TNF alpha) in patients with rheumatic diseases. We tested sera from patients with rheumatoid arthritis, seronegative arthritis, osteoarthritis, post-traumatic arthritis, systemic lupus erythematosus, progressive systemic sclerosis and normal healthy subjects as controls. Furthermore, we statistically analysed data to investigate whether a correlation exists between serum levels of TNF alpha and some humoral indexes of disease activity. The results show strikingly higher TNF alpha levels in Rheumatoid Arthritis patients when compared both to normal controls and arthritis or connective tissue disease controls. TNF alpha was also found to correlate positively with levels of the rheumatoid factor as measured either by means of the latex agglutination test (LAT) or by nephelometry. These results support the suggestion that TNF alpha plays a central role in the pathogenesis of rheumatoid arthritis.

Differential expression of IL-1 and TNF receptors in inflammatory arthritis and osteoarthritis.

Pathological joint events in both inflammatory arthritis and degenerative arthritis are perpetuated by complex cytokine interactions. Two cytokines, IL-1 and TNF alpha, appear to be the major culprits in the pathogenesis of synovitis and in cartilage damage in these joint diseases. To analyze the expression of IL-1 and TNF alpha and their receptors on synovial and cartilage tissue, we performed an immunohistochemical study on knee biopsies from patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and osteoarthritis (OA). Results identified a prevalent positivity to cytokines and their receptors of synovial cells from RA and PsA with respect to OA patients. In cartilage specimens, most RA and PsA patients showed no expression of the studied receptors, whereas the majority of OA biopsies were positive for all types of examined receptors except IL-1R2. Our study suggests that the cartilage is the main target of these cytokines in OA, while in IA IL-1 and TNF alpha exert their action in synovial tissue. In all the studied pathologies (RA, PsA, OA) the synovial tissue and the cartilage were differentially involved, indicating the importance of investigating both structures in joint disease studies.

Leukocyte infiltration in synovial tissue from the shoulder of patients with polymyalgia rheumatica. Quantitative analysis and influence of corticosteroid treatment.

OBJECTIVE: To investigate the immunologic features of synovitis in patients with polymyalgia rheumatica (PMR) and to assess the modifications induced by corticosteroids. METHODS: Arthroscopic biopsies of shoulder synovium were obtained from 12 patients with untreated PMR and from 7 patients with PMR that had been treated. Immunohistochemistry was performed on frozen sections utilizing a panel of monoclonal antibodies and computerized image analysis. RESULTS: Synovitis was present in 10 of 12 (83%) untreated patients and in only 2 of 7 (29%) treated patients. The synovitis was characterized by vascular proliferation and leukocyte infiltration. Infiltrating cells consisted predominantly of macrophages and T Lymphocytes. Almost all T lymphocytes were CD45RO positive. A few neutrophils, but no B cells, natural killer cells, or gamma/delta T cells were found. Intense expression of HLA class II antigens (DR moreso than DP moreso than DQ) was found in the lining layer cells as well as in macrophages and lymphocytes. DR, but not DP or DQ, was expressed by the endothelium of a few vessels. Class II antigen expression correlated with the number of macrophages and lymphocytes. Macrophage infiltration of arteriole walls was observed in 1 untreated patient without giant cell arteritis (GCA). In untreated patients, there was a positive correlation between the percentage of infiltrating T cells and the duration of disease. Steroid therapy was associated with a significant reduction in the number of blood vessels and of HLA class II expression. One treated patient who no longer had symptoms of PMR still had active synovitis: a relapse occurred 4 months after the biopsy. CONCLUSION: Our findings support the hypothesis that synovitis is a major cause of the musculoskeletal symptoms of PMR. There are immunologic similarities with the vascular inflammation observed in GCA. Corticosteroids act on both the vascular and cellular components of synovitis.

Synovial expression of cell adhesion molecules in polymyalgia rheumatica.

Polymyalgia rheumatica (PMR) is a common disorder of the elderly: the pathogenesis of the syndrome is still debated, though active synovitis of the shoulder has recently been confirmed. To investigate the pathogenesis of this synovitis we evaluated cell adhesion molecule (CAM) expression in shoulder synovial tissue from patients with PMR, correlated synovial expression with the serum levels of soluble forms, and assessed the changes associated with corticosteroid treatment. Arthroscopic synovial biopsies were obtained from 12 untreated and seven corticosteroid (CS)-treated cases. CAM expression was evaluated by MoAb staining on frozen sections and computerized image analysis. Soluble CAM were quantified by ELISA. Endothelial cells expressed intercellular adhesion molecule-1 (ICAM-1), E- and P-selectins. Infiltrating cells were ICAM-1 and beta1-integrin-positive, while L-selectin expression was limited to intravascular leucocytes. Synovial lining cells strongly expressed vascular cell adhesion molecule-1 (VCAM-1), and less intensely ICAM-1. Only the soluble form of ICAM-1 (sICAM-1) was elevated in untreated patients. CS treatment was associated with a decrease in ICAM-1, VCAM-1 and E- and P-selectin expression. sICAM-1 levels were in the normal range in treated patients. VLA-5 and 6 expression was widely distributed among cell types, and was not CS-sensitive. Active shoulder synovitis is associated with different CAM expression in PMR. ICAM-1 expression is widely distributed and correlates with elevated levels of the soluble form; it is significantly lower in CS-treated asymptomatic cases.