Fine-structural changes of the synovial membrane in arthrosis deformans

Summary The known light microscopic findings in the inner part of joint capsules in arthrosis have largely been verified and in part supplemented by scanning and transmission electron microscopic examinations. Whereas in arthrosis of the hip joint sclerosis of the synovial membrane predominates with atrophy of the layer of lining cells, in arthrosis of the knee joint more polymorphic structures of the surface occur with variable but moderate hyperplasia and hypertrophy of the synovial cells. Inflammatory cell proliferations and infiltrates of the same degree as in non-specific arthritis and rheumatoid arthritis were not observed. Thus, the absence both of characteristic changes of the individual synovial cells and of more extensive inflammatory infiltrates in association with atrophy and sclerosis of the synovial folds may be regarded as an indirect indication of the synovial reaction in arthrosis deformans.

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Zusammenfassung Durch raster- und transmissionselektronenmikroskopische Untersuchungen ausgedehnten Synovektomie-Materials wurden die bekannten lichtmikroskopischen Befunde an der inneren Gelenkkapsel weitgehend bestätigt und teilweise ergänzt. Während bei chronischer Coxarthrose die Sklerose der Synovialmembran mit Atrophie der inneren gelenkauskleidenden Zellschicht im Vordergrund steht, kommen bei Gonarthrose polymorphere Oberflächenstrukturen mit wechselnder, im ganzen aber mäßiger Hyperplasie und Hypertrophie der Synovialzellschicht vor. Entzündlich-hyperplastische überschießende Zellproliferationen und Infiltrate wie bei unspezifischer Arthritis und rheumatoider Arthritis werden bei Arthrosis deformans nicht beobachtet. Das Fehlen charakteristischer Veränderungen der einzelnen Synovialzellen und das Fehlen eindeutiger entzündlicher Infiltrate werden zusammen mit der Sklerose und Atrophie der Synovialfalten als indirekter Hinweis auf eine synoviale Reaktion auf arthrotische Gelenkveränderungen gewertet.

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Herrn Prof. Dotzauer zum 60. Geburtstag.     

Antikeratin antibodies in synovial fluid in rheumatoid arthritis

Serum and synovial fluid of 20 patients with classical or definite rheumatoid arthritis (RA) were tested for antikeratin antibodies (AKA) by indirect immunofluorescence using rat esophagus as antigen. AKA were found in 80% of the RA patients, in serum as well as in synovial fluid. None of the 54 serum control patients were AKA positive in serum. None of the 17 synovial fluid control patients were AKA positive in synovial fluid. F(ab)'2 fragments prepared from AKA positive RA serum retained antibody activity. AKA belonged to the IgG class of immunoglobulins. Corrected for the lower IgG content in synovial fluid, AKA constituted a higher percentage of the IgG in synovial fluid than in serum. This could imply a possibility of local production of AKA in the joint.     

A study of opioid peptides in synovial fluid and synovial tissue in patients with rheumatoid arthritis]

Authors have often experienced that psychological stress influences rheumatoid arthritis (RA). In addition, recent reports show a modulatory role for neuropeptide such as substance P in arthritis. These findings prompted us to study endogenous opioid peptides in RA, which are found mainly in the brain and have an effect on the central nervous system. We examined methionine-enkephalin (Met-enk), leucine-enkephalin (Leu-enk) and beta-endorphin (beta-end) in opioid peptides. We measured these peptides in plasma and synovial fluid samples obtained from 28 knees of 24 RA patients and the quantity in the synovial tissue of 13 knees. We also measured plasma and synovial fluid samples from patients with osteoarthritis of the knee and plasma samples from healthy candidates. Leu-enk and beta-end levels in synovial fluid were significantly higher than plasma levels only in RA. Larger quantity of Leu-end and beta-end were contained apparently in the synovial tissue than Met-enk. The synovial tissue with proliferative change tends to contain larger quantity of opioid peptides. These results indicate that the synovial tissue produces or secretes Leu-enk and beta-end and that opioid peptides are related to the degree of inflammation in RA.     

GSDMD-N和p-MLKL蛋白在类风湿关节炎滑膜组织中上调

目的 探索类风湿关节炎(RA)患者膝关节滑膜组织中细胞焦亡标志性蛋白GSDMD-N和程序性坏死标志性蛋白p-MLKL的表达水平和意义.方法 记录入组患者临床资料,包括性别、年龄、红细胞沉降率(ESR)和超敏C反应蛋白(hsCRP).对RA和骨关节炎(OA)滑膜HE染色,用Krenn评分评估病理滑膜炎程度.提取RA和OA...     

Polyamine oxidase activity in rheumatoid arthritis synovial fluid.

Oxidation of polyamides by polyamine oxidases (PAO) leads to the generation of highly reactive aminoaldehydes which have been shown to have a variety of effects, including killing of pathogenic microorganisms and regulation of leucocyte functions. Data presented here show that PAO are present in synovial fluid from patients with rheumatoid arthritis. This finding may have important implications in the various properties attributed to synovial fluid which includes anti-inflammatory activity.     

T cell receptor gene in synovial tissues of rheumatoid arthritis

Rheumatoid arthritis is a chronic and destructive autoimmune joint disease characterized by inflammation of synovial tissue of unknown aetiology. Studies on TCR genes expressed by infiltrating T cells in synovial tissues have attempted to identify mechanism and specificity of the recruitment. T cell infiltrate in rheumatoid arthritis appears to be an association of a polyclonal non specific infiltrate with dominant clones or clonotypes. T cell repertoire in synovial tissue is biased compared to peripheral blood but no TCR V gene can be identified as commonly over-used. Comparison of motifs found in the CDR3 region of dominant clones from different studies has currently failed to identified a commonly motif. The fact that a number of dominant clones or clonotypes is present in different joints and at different times of the disease suggests a selective expansion of T lymphocytes in rheumatoid arthritis synovial membrane. Further investigations are needed to characterize the specificity of these dominant clonotypes.     

Production of PAF-acether by synovial fluid neutrophils in rheumatoid arthritis

PAF-acether (PAF) is a pro-inflammatory phospholipid molecule potentially involved in the pathogenesis of arthritis. PAF and related metabolites have been isolated in the synovial fluid from patients with arthritis.The aim of this study was to determine PAF production by neutrophils isolated from synovial fluid and blood in patients with rheumatoid arthritis. Blood neutrophils from normal donors were also studied for their capacity to form PAF. Neutrophils were stimulated with the calcium ionophore A23187 (2µM) for 1 to 60min. PAF released in the medium and PAF associated to cells were measured.In synovial fluid neutrophils, PAF production began as soon as 1 min of stimulation (16.1 ± 6.3 pmol per 1 × 10⁶ cells) and reached a maximum at 20min: 29.2 ± 2.8 pmol per 1 × 10⁶ cells (mean ± SEM, n = 5). The amount of PAF released in the supernatant increased with the length of stimulation and was maximal after 30min (33.5%, percentage of released over total PAF, n = 5). After A23187 stimulation, similar amounts of PAF were produced by blood neutrophils from RA and control patients. However, neutrophils isolated from the joint had a lower capacity to produce PAF than blood neutrophils from the same patients.The present results demonstrate the synthesis and release of PAF by synovial fluid neutrophils. They suggest that neutrophils may be the source of PAF locally present in the joint. Newly synthetised PAF could participate in the amplification of the local inflammatory reaction.     

Electrophoretic behaviour of blood and synovial fluid lymphocytes in rheumatoid arthritis.

Probit analysis of the electrophoretic mobilities of human blood lymphocytes identifies at least three main subpopulations. According to their rate of movement in an electrical field, the subpopulations are referred to as the fast, intermediate and slow cell distributions. Lymphocytes of the fast and intermediate populations appear to be T cells, while the slow cell population includes cells with B cell characteristics. Compared with normal subjects, lymphocytes of intermediate mobility are significantly increased in the blood of rheumatoid patients and comprise a major fraction of the lymphocyte exudate in rheumatoid synovial fluid.     

B和T淋巴细胞衰减因子(BTLA)在类风湿关节炎滑膜组织的表达

目的:探讨CD28家族共抑制分子B和T淋巴细胞衰减因子在类风湿关节炎(RA)患者滑膜组织内的表达。方法:免疫组化法检测RA患者滑膜组织BTLA的表达;并使用免疫荧光法检测BTLA的细胞定位及分布。结果:免疫组化结果证实,RA患者滑膜组织中有大量的BTLA阳性细胞,形态观察提示这些阳性的细胞主要是淋巴结处的淋巴细胞及巨噬细胞;免疫荧光分析进一步表明这些BTLA+细胞主要为CD3+T细胞及CD68+巨噬细胞,少数CD31+内皮细胞也表达BTLA。此外,对比其他B7家族共刺激分子在滑膜组织中的分布,免疫荧光发现BTLA共表达于B7-H1+,B7-H4+及HVEM+细胞,但不表达于B7-DC+及B7-H3+细胞。结论:关节炎滑膜组织内有大量BTLA阳性细胞,提示BTLA有可能参与并调节了关节炎的病理进程。     

共刺激分子HVEM在类风湿关节炎滑膜组织内的表达及分布研究

目的探讨TNF家族共刺激分子HVEM(herpesvirus entry mediator)在类风湿关节炎(RA)患者滑膜组织内的表达及分布。方法使用免疫组化法检测RA患者滑膜组织HVEM的表达;并使用免疫荧光法检测HVEM的细胞定位及分布。结果免疫组化结果证实,RA患者滑膜组织中有大量的HVEM阳性细胞,形态观察提示这些阳性的细胞主要是毛细血管、滑膜细胞、局部淋巴结T细胞及巨噬细胞;免疫荧光分析进一步表明这些HVEM+细胞主要为CD3+T细胞,CD68+巨噬细胞,少数CD31+内皮细胞也表达HVEM,但其不表达于CK-18+上皮细胞。对比其他B7家族共刺激分子在滑膜组织中的分布,免疫荧光发现HVEM共表达于B7-H3+血管,但不表达于B7-H1+、B7-DC+、B7-H4+及Z39Ig+细胞。结论关节炎滑膜组织内有大量HVEM阳性细胞,提示HVEM有可能参与并调节了关节炎的病理进程。     

Distribution of activated B lymphocytes in the circulation and synovial fluid in rheumatoid arthritis

The circulating peripheral blood of 13/28 patients with definite or classical rheumatoid arthritis (RA) had increased numbers of spontaneous in vivo active immunoglobulin-producing B lymphocytes detected by a reverse hemolytic PFC assay (mean = 3000 (1310-7920) Ig PFC/10(6) B cells) compared to an age/sex-matched control population (mean = 550 (300-900) Ig PFC/10(6) B cells). Among the remaining 16 RA patients who had normal numbers (less than 900 Ig PFC/10(6)) of such circulating B cells, 5 patients had increased numbers of activated B cells in the synovial fluid and 6 patients had no increase. Extraarticular features (nodules and vasculitis) in 11/13 patients and advanced but relatively inactive synovitis characterized those RA patients with increased numbers of active circulating B cells. In contrast, extraarticular features were seldom observed (1/16) among the remaining patients with normal numbers of active circulating B cells. Among these patients, more active generalized synovitis characterized those patients with increased numbers of active synovial fluid B cells compared to those patients with normal numbers. These studies imply that in RA patients, whose disease is primarily articular, active Ig synthesis is limited to the synovial compartment, while in those with extraarticular features active Ig-producing B cells also appear in the circulation.     

Elevated expression of TAM receptor tyrosine kinase in synovial fluid and synovial tissue of rheumatoid arthritis

To investigate the expression and roles of TAM (Tyro3/Axl/Mer) receptor tyrosine kinases (TK) in synovial fluid and synovial tissue of patients with rheumatoid arthritis (RA). The expression of TAM TKs in the synovial fluid and synovial tissues of RA and osteoarthritis (OA) patients was measured by ELISA and immunohistochemistry. The relationships between soluble TAM TKs (sTAM TKs) levels and the clinical features, laboratory parameters and disease activity were analyzed in RA. The concentrations of sTAM TK in the synovial fluids of RA patients were increased in comparison to those of OA patients. Compared with OA patients, the expression of membrane Tyro3 TK (mTyro3 TK) and mMer TK in RA patient synovial tissue were significantly increased, which may partly explain the possible mechanism of elevated levels of sTAM TK in RA patient synovial fluid. sAxl TK levels were decreased in RA patients under sulfasalazine treatment and elevated in patients under Iguratimod treatment. Furthermore, sTyro3 TK levels were positively correlated with erythrocyte sedimentation rate (ESR) and negatively correlated with white blood cells (WBCs), red blood cells (RBCs), and hemoglobin (HB) in RA patients. The levels of sMer TK were positively associated with disease duration and rheumatoid factor (RF) and negatively correlated with HB, complement 3 (C3), and C4. Taken together, TAM TKs might be involved in RA synovial tissue inflammation.