Journal Article•
In vivo synthesis of IgG by rheumatoid synovium.
01 Aug 1970-Journal of Laboratory and Clinical Medicine (J Lab Clin Med)-Vol. 76, Iss: 2, pp 304-310
About: This article is published in Journal of Laboratory and Clinical Medicine.The article was published on 1970-08-01 and is currently open access. It has received 91 citations till now. The article focuses on the topics: In vivo.
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TL;DR: In an infectious etiology of rheumatoid arthritis, it is pertinent to consider the manner in which a pathogen might gain access to the synovial membrane, as the joint seems to be uniquely predisposed to infection with some bacteria.
Abstract: Publisher Summary This chapter focuses on the pathogenesis of rheumatoid arthritis. In an infectious etiology of rheumatoid arthritis, it is pertinent to consider the manner in which a pathogen might gain access to the synovial membrane. The joint seems to be uniquely predisposed to infection with some bacteria. Rheumatoid synovitis is characterized by a constellation of histological changes, which are characteristic but not pathognomonic of this disease. In hypertrophy of the synovial lining surface, the synovium appears edematous and inflamed and protrudes into the joint space as slender villous projections. In hyperplasia and hypertrophy of the synovial lining cells, the lining cells are multilayered, reaching to a depth of six to ten cells, as compared to the normal synovial lining that is only one to three cell layers. Vascular derangement—focal or segmental vascular changes—are a regular feature of rheumatoid synovitis. Cellular infiltrates—the connective tissue stronia of the synovial villus is packed with mononuclear cells—are collected into aggregates or follicles, particularly around small blood vessels, but true germinal centers are rarely seen.
540 citations
TL;DR: A detailed morphologic and serologic analysis of this disease revealed a 75% incidence of synovial and periarticular inflammation in 5-6 mo-old females and a close correlation between presence of circulating IgM rheumatoid factor (RF) and demonstrable synovia and/or joint pathology.
Abstract: MRL/l mice spontaneously develop an arthritis very similar in many respects to human rheumatoid arthritis. A detailed morphologic and serologic analysis of this disease revealed the following: (a) a 75% incidence of synovial and periarticular inflammation, very similar to human rheumatoid arthritis, in 5-6 mo-old females, (b) close associations between presence of joint inflammation and subsynovial and/or periarticular vasculitis, and (c) a close correlation between presence of circulating IgM rheumatoid factor (RF) and demonstrable synovial and/or joint pathology, i.e., 95% of mice with significant levels of IgMRF had synovitis and/or arthritis.
313 citations
TL;DR: AFA‐secreting plasma cells are present in the synovial tissue of RA patients and AFA can represent a significant proportion of the IgG secreted within the rheumatoid pannus.
Abstract: IgG anti-filaggrin autoantibodies (AFA) are the most specific serological markers of rheumatoid arthritis (RA). They include the so-called 'anti-keratin antibodies' (AKA) and anti-perinuclear factor (APF), and recognize human epidermal filaggrin and other (pro)filaggrin-related proteins of various epithelial tissues. In this study we demonstrate that AFA are produced in rheumatoid synovial joints. In 31 RA patients, AFA levels were assayed at equal IgG concentrations in paired synovial fluids (SF) and sera. AFA titre-like values determined by indirect immunofluorescence and immunoblotting and AFA concentrations determined by ELISA were non-significantly different in serum and SF, clearly indicating that AFA are not concentrated in SF. In contrast, we demonstrated that AFA are enriched in RA synovial membranes, since the ELISA-determined AFA in low ionic-strength extracts of synovial tissue from four RA patients represented a 7.5-fold higher proportion of total IgG than in paired sera. When small synovial tissue explants from RA patients were cultured for a period of 5 weeks, the profile of IgG and AFA released in the culture supernatants was first consistent with passive diffusion of the tissue-infiltrating IgG (including AFA) over the first day of culture, then with a de novo synthesis of IgG and AFA. Therefore, AFA-secreting plasma cells are present in the synovial tissue of RA patients and AFA can represent a significant proportion of the IgG secreted within the rheumatoid pannus.
230 citations
TL;DR: The findings indicate that the immune complexes sequestered in rheumatoid cartilage contain autoantibodies that are probably synthesized locally by cells infiltrating the inflamed synovium, which would provide a possible pathogenic mechanism that explains the self-perpetuating and chronic nature of cartilage degradation in r heumatoid arthritis and osteoarthritis.
Abstract: To define autoantibody specificities of immune complexes sequestered in articular cartilage of patients with rheumatoid arthritis and osteoarthritis, extracts were obtained from articular cartilage specimens from 16 patients with rheumatoid arthritis, 11 patients with osteoarthritis, and 6 normal controls. Radioimmunoassays of the extracts revealed that rheumatoid cartilage contained 37 times more IgM and 14 times more IgG than did normal cartilage extracts. In addition, osteoarthritic cartilage contained 3 times more IgM and IgG than the normal tissues. IgM rheumatoid factor was found in 13 of 16 rheumatoid cartilage extracts but in none of 11 osteoarthritic or 6 normal control extracts. IgG rheumatoid factor was detected in 4 of 7 seropositive rheumatoid but in none of 5 osteoarthritic cartilage extracts. More than 60% of the rheumatoid cartilage extracts were positive for native and denatured collagen II antibodies. Surprisingly, 50% of the osteoarthritic specimens also contained significant titers of collagen antibodies. Similar results were obtained with osteoarthritic menisci extracts. These findings indicate that the immune complexes sequestered in rheumatoid cartilage contain autoantibodies that are probably synthesized locally by cells infiltrating the inflamed synovium. If immune complexes trapped in cartilage play an important role in cartilage damage, our findings would provide a possible pathogenic mechanism that explains the self-perpetuating and chronic nature of cartilage degradation in rheumatoid arthritis and osteoarthritis.
203 citations
TL;DR: It is striking that this structural change in IgG carbohydrate, which may facilitate the self-association of IgG rheumatoid factors and contribute to autoantigenicity, should be restricted to such a small number of diseases.
200 citations