Effect of Dexamethasone and Nitrogen Mustard on the Production of Rheumatoid Factor in Rheumatoid Arthritis

The effect of dexamethasone and nitrogen mustard on the production of rheumatoid factor, as measured by sensitized sheep cell and latex agglutination tests, was studied in 19 patients with classical rheumatoid arthritis. Dexamethasone was given orally in a daily dose of 6-8 mg. which was slowly reduced after a two-week period. Nitrogen mustard was infused in the usual therapeutic dose of 0.3 mg./kg. The level of circulating rheumatoid factor decreased, following administration of each agent, after a latent period of 10 days. The effect was most marked at around 30 days. Dexamethasone was more potent than nitrogen mustard. Both drugs together caused transient disappearance of rheumatoid factor in one patient.It is concluded that dexamethasone and nitrogen mustard have the capacity to suppress the formation of the macroglobulins associated with rheumatoid arthritis.     

Antibody-bearing liposomes improve agglutination of latex particles used in clinical diagnostic assays

Ligand-bearing liposomes are used to enhance the agglutination ‘signal’ of a typical latex assay for the detection of human rheumatoid factor. Heat-denatured IgG, the antigen to which rheumatoid factor binds naturally, was covalently attached to latex spheres. The liposomes were covalently coated with a ‘second ligand’ which also recognizes rheumatoid factor, anti-human IgM Fab′ fragments. In the present test configuration, rheumatoid factor present in a patient's serum binds to the IgG attached to the latex particles. The liposomes, in turn, bind rapidly to rheumatoid factor-sensitized latex, via the second ligand, promoting the formation of large, clearly visible latex aggregates. When latex spheres bearing the same type and density of second ligand were used to replace the liposomes they failed to improve agglutination, suggesting that multivalent presentation of the second ligand is not sufficient to insure the improvement. These results suggest that fluidity of the liposomal membrane is a requirement for the effect. Sensitivity as well as ‘readability’ are improved by the liposomes while specificity remains unaffected. The principle of using ligand-bearing liposomes to enhance particle agglutination is applicable to a wide range of other diagnostic assays.     

Autoantibodies and the Hepatitis-associated Antigen in Acute Infective Hepatitis

In 39 unselected patients with acute infective hepatitis diagnosed on clinical, epidemiological, and pathological findings, smooth muscle (S.M.) antibody was found in 87% and hepatitis-associated antigen in 33%. The incidence of S.M. antibody was highest during the first month after the onset of symptoms, and the antibody was preponderantly IgM at this stage.S.M. antibody and hepatitis-associated antigen occurred independently, and unlike hepatitis-associated antigen, which was strongly associated with possible parenteral exposure to infection, the incidence of S.M. antibody was not related to the presumed mode of exposure. It is concluded that production of S.M. antibody is more directly related to liver cell damage than to the presence of hepatitis-associated antigen in the serum.     

感染与类风湿性关节炎

类风湿性关节炎(RA)等风湿性疾病的原因尚不明确(风湿热除外),目前研究发现RA的发病与遗传因素和环境因子(特别是病毒)有关。RA的发病与微生物感染密切相关,任何感染都可引起RA恶化,但迄今尚未确切地从病人血与滑液中找到活的微生物。多数学者认为微生物抗原在类风湿的发病中起始动作用。     

Hepatitis-associated Antigen and Antibody in Haemodialysis Patients and Staff

The screening of a dialysis population for the presence of hepatitis-associated antigen (H.A. antigen) has proved to be of value in locating a probable source of infection and in terminating an outbreak of hepatitis by early detection of H.A. antigen positive patients and staff.     

The occurrence of hepatitis-associated antigen in a group of Canadian patients with leukemia

Serial blood samples from 37 Nova Scotian patients with different forms of leukemia and other malignant conditions of bone marrow and lymphoid tissue were tested for the hepatitis-associated antigen (HAA). Ten patients were found to be positive for HAA. Not only is there an increased incidence of HAA in this population group, but when present the antigen is carried for a longer period than in the normal individual. The increased incidence was completely unrelated to the blood transfusion histories of the patients.     

Rheumatoid arthritis specific anti-Sa antibodies target citrullinated vimentin

Antibodies directed to the Sa antigen are highly specific for rheumatoid arthritis (RA) and can be detected in approximately 40% of RA sera. The antigen, a doublet of protein bands of about 50 kDa, is present in placenta and in RA synovial tissue. Although it has been stated that the Sa antigen is citrullinated vimentin, experimental proof for this claim has never been published. In this study, we investigated the precise nature of the antigen. Peptide sequences that were obtained from highly purified Sa antigen were unique to vimentin. Recombinant vimentin, however, was not recognized by anti-Sa reference sera. In vivo, vimentin is subjected to various post-translational modifications, including citrullination. Since antibodies to citrullinated proteins are known to be highly specific for RA, we investigated whether Sa is citrullinated and found that Sa indeed is citrullinated vimentin. Anti-Sa antibodies thus belong to the family of anticitrullinated protein/peptide antibodies. The presence of the Sa antigen in RA synovial tissue, and the recent observation that vimentin is citrullinated in dying human macrophages, make citrullinated vimentin an interesting candidate autoantigen in RA and may provide new insights into the potential role of citrullinated synovial antigens and the antibodies directed to them in the pathophysiology of RA.     

Low Incidence of Rheumatoid Factor and Autoantibodies in Nigerian Patients with Rheumatoid Arthritis

Sera from 53 Nigerian patients satisfying the American Rheumatism Association criteria for a diagnosis of definite or probable rheumatoid arthritis and sera from sick and healthy Nigerian controls were tested for rheumatoid factor, autoantibodies, and immunoglobulin levels. Rheumatoid factor and autoantibodies were found no more frequently in patients with rheumatoid arthritis than in controls. These findings confirm the clinical impression that Nigerian patients with polyarthritis satisfying the criteria for a diagnosis of rheumatoid arthritis differ from Caucasian patients with the disease in a number of important respects. They suggest that either these patients do not have rheumatoid arthritis but a distinct clinical syndrome or that in Nigeria the course of rheumatoid arthritis is modified by genetic or environmental factors.     

Rheumatoid factors induce signaling from B cells, leading to Epstein-Barr virus and B-cell activation

B-cell antigen receptor signaling is initiated upon binding of the antigen to membrane-bound immunoblobulin (Ig), and the anti-Ig antibody (Ab) mimics this signaling. In B cells latently infected with Epstein-Barr virus (EBV), the same signals induce virus activation. We examine here whether rheumatoid factors (RFs), autoantibodies directed against the Fc portion of IgG, induce EBV and B-cell activation. As a source of RFs, RF-producing lymphoblastoid cell line (LCL) clones were isolated from peripheral blood mononuclear cells (PBMC) and synovial cells from patients with rheumatoid arthritis (RA) by EBV transformation. Burkitt's lymphoma-derived Akata cells, which are highly responsive to EBV activation by anti-Ig Abs, were used for the assay of EBV activation. Akata cells expressed IgG3 as membrane-bound Ig. RFs from a synovium-derived LCL were directed to IgG3 and induced EBV activation in 16 to 18% of Akata cells, whereas RFs from another synovium-derived LCL were directed to IgG1 and did not induce EBV activation. Pretreatment of RFs with the purified Fc fragment of human IgG completely abolished EBV activation. Furthermore, B-cell activation was assessed by incorporation of [3H]thymidine. RFs from synovium-derived LCLs efficiently induced B-cell activation, and the addition of CD40 ligand had a synergistic effect. On the other hand, RFs from PBMC-derived LCLs were polyreactive, had a lower affinity to IgG, and did not induce EBV and B-cell activation. The present findings imply a possible role for RFs as EBV and B-cell activators.     

Primary Hepatoma and Hepatitis-associated Antigen in a Young White Woman

A young woman whose serum was positive for hepatitis-associated antigen (H.A.A.) and alpha-fetoprotein developed a malignant hepatoma. Though the light-microscopical appearances of the surrounding liver tissue were normal, electronmicroscope examination of the tumour tissue disclosed both C-virus-like particles and H.A.A. particles. Possibly there was a causal connexion between one of these particles and the hepatoma.     

Relative Sensitivity of Gel Diffusion, Complement Fixation, and Immunoelectroosmophoresis Tests for Detection of Hepatitis-Associated Antigen and Antibody

The immunoelectroosmophoresis (IEOP) test was compared with gel diffusion and complement fixation (CF) tests for sensitivity in detecting hepatitis-associated antigen (HAA) in the sera of hepatitis patients, for titration of HAA, and for detection of antibody to HAA. The IEOP test was found to be slightly more sensitive than either gel diffusion or CF tests for detection of antigen in the patients' sera. Titers of HAA demonstrated by IEOP were higher than those seen in gel diffusion tests but lower than CF titers. The gel diffusion test with an "enhancement" pattern was found to be more reliable than the other two procedures for detection of low levels of anti-HAA, due to the greater inhibitory effect of an antigen excess in the IEOP system and the possible masking of low levels of antibody by anticomplementary activity in the CF test system. Staining of immunoprecipitates in the IEOP test contributed little to the sensitivity of the test for detection of HAA.     

Assay of rheumatoid factors by the indirect immunofluorescence method

Sera from 69 patients affected with rheumatoid arthritis were examined for IgM, IgG and IgA rheumatoid factors (RF) by a indirect immunofluorescence method. The results were compared with those obtained from the classical rheumatoid factor latex test. By this technique we have demonstrated antigammaglobulin activity in a high proportion (23%) of sera from latex test seronegative rheumatoid patients. Moreover, by fractionated antisera it was possible to detect also IgG and IgA factors. Indirect immunofluorescence results to be a simple and available technique for detection of RF, also in many "seronegative" patients.     

Rheumatoid nodules

Summary The presence and localization of fibrin and fibronectin in rheumatoid nodules were studied using an indirect immunoperoxidase technique on tissue specimens fixed in formaldehyde, embedded in paraffin and pretreated with pepsin and testicular hyaluronidase. Three zones characteristic for rheumatoid nodules was recognized. 1) Central area with necrosis, containing at least in part fibrinogen-antigenic material and fibronectin especially in the peripheral part of the necrotic area. 2) Around the necrosis a layer of mesenchymal cells in a palisade arrangement was found. Especially in the external part of this layer fibronectin was demonstrated around and between the cells, where fibrin was absent. 3) Peripherally, a zone of non-specific granulation tissue containing moderate amount of fibronectin decreasing towards the surround mature connective tissue, was seen. In the border of the cellular layer vessels were found in variable amount. In some of the vessels vasculitis was demonstrated with the presence of inflammatory cell infiltration, fibrin deposition and occasionally thrombosis. The pathogenesis of the inflammatory reaction in rheumatoid nodules is discussed.     

Immunological Studies in Ugandan Patients with Hepatocellular Carcinoma

Immunological studies were performed on Ugandan patients with hepatocellular carcinoma to test the hypothesis that the high rate of persistence of hepatitis-associated antigen in these patients is the result of defects in host immune response. The responses to 1-chloro-2,4-dinitrobenzene sensitization and to a battery of recall skin test antigens were normal, as was the humoral antibody response to tularaemia antigen. Neither hypogammaglobulinaemia nor specific immunoglobulin deficiencies were found. Thus it appears unlikely that generalized defects in host immune responses can account for the high incidence of persistent hepatitis B virus infection found in Ugandan patients with hepatocellular carcinoma.     

Rheumatoid involvement of the aortic arch

The clinical course of rheumatoid arthritis may be complicated by cardiac involvement. Indeed, postmortem studies suggest rheumatoid involvement in up to 50% of pericardial, 5% of myocardial, and 60% of valvular specimens. Yet, in our search of the literature, we found only a single case report describing aortic valve replacement for rheumatoid valvulitis. This discrepancy may be related to the paucity of symptoms in this sedentary group of patients. A complete cardiac evaluation of patients with rheumatoid arthritis is recommended to select those with significant valvular involvement for timely surgical intervention prior to the development of irreversible left ventricular dysfunction. Two patients who benefitted from aortic valve replacement for rheumatoid valvular disease are presented.     

Rheumatoid arthritis and Dupuytren's contracture

Of four patients with rheumatoid arthritis and Dupuytren's contracture, two were not aware of the presence of Dupuytren's contracture. When both diseases coexist, the presence of rheumatoid hand deformities, especially flexion and ulnar deviation of the metacarpophalangeal joints, may mask the flexion deformity caused by Dupuytren's contracture. Careful clinical examination should rule out the presence of a pathologic fascial cord. When reconstructive surgery is indicated for the rheumatoid hand in the presence of advanced Dupuytren's contracture, staged surgery would be appropriate and reconstruction of Dupuytren's contracture should precede other surgery.     

Pernicious Anaemia and Rheumatoid Arthritis

In a study of 99 patients with pernicious anaemia the incidence of clinical rheumatoid arthritis was normal but rheumatoid factor was present significantly more often than in controls. This was not related to the presence of circulating antibody to intrinsic factor.Intrinsic factor antibody was not detected in any of 151 latex-fixation-positive rheumatoid sera.     

骨质疏松标志物在评价类风湿关节炎骨代谢及侵蚀作用的临床研究

目的：探讨I型胶原交联羧基氨基端肽(beta-Crosslaps)和总骨1 型前胶原氨基端延长肽（P1NP）及C- 反应蛋白（CRP）在类风湿 性关节炎骨质疏松发生与骨侵蚀程度评价中的作用。方法：运用电化学发光法对茁-Cross Laps、P1NP进行定量检测。用胶乳散射 比浊法进行CRP 定量检测。将65 例类风湿关节炎患者按有无骨质破坏分为早期组和非早期组,按活动性分为缓解组与活动组, 按骨影像学显示分为骨侵蚀组与非骨侵蚀组。并取30 例健康体检者作为对照组。结果：三种标志物在早期RA 组与非早期RA 组 之间及在活动组与缓解组、骨侵蚀组与非骨侵蚀组比较具有显著差异,差异有统计学意义（P<0.01）。结论：beta-Cross laps、P1NP、 CRP三种骨质疏松标志物可以用作评价RA骨代谢水平和骨侵蚀程度的良好指标,并还可以运用于疗效监测,有较好的临床应用价 值。     

Rheumatoid arthritis viewed using a headache paradigm

Results and new hypotheses in animal models often stimulate development of new paradigms in how we view rheumatoid arthritis (RA). The complexity of RA does, however, eventually lead to the rejection of these hypotheses. Here, it is argued that the large number of so-far described animal models, when taken together, also reveals a complex disease. Fortunately, detailed study of each of the animal models will reveal this complexity, and may also be helpful in elucidating the complexity of the human disease. Benoist and Mathis [1] recently contributed a new animal model in which an autoimmune response to a ubiquitous antigen leads to an antibody-mediated inflammatory attack in the joints. It is argued that this new model, as with other animal models, is unlikely to explain RA, but it will add to the tools available to reveal the complexity of RA.     

Rheumatoid synovium: its proliferation, heterogeneity and polarization

All of the changes observed suggest that a viral agent may form the basis for these alterations [in rheumatoid synovium]. However, studies to date have failed to isolate or identify the putative causative virus and the search continues.