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PubMed2006

Up regulation of monocyte chemoattractant protein-1 expression in anti-citrulline antibody and immunoglobulin M rheumatoid factor positive subjects precedes onset of inflammatory response and development of overt rheumatoid arthritis.

OBJECTIVE: To analyse the inflammatory mediators, including monocyte chemoattractant protein-1 (MCP-1), in blood samples donated years before onset of rheumatoid arthritis. Previously, it has been shown in these individuals that antibodies against cyclic citrullinated peptide (anti-CCP) detectable years before the onset of symptoms have a high predictive value for development of rheumatoid arthritis. METHODS: A nested case-control study was performed: patients with rheumatoid arthritis were identified from among blood donors antedating onset by a median of three years (pre-patients, n = 92); four matched controls were selected randomly for each pre-patient. Plasma were analysed for secretory phospholipase A2 (sPLA2) and MCP-1 using ELISA, for high-sensitivity C reactive protein (hsCRP) using the chemiluminescence method and for interleukin-6 using a sensitive bioassay. RESULTS: When the results were stratified for the presence of anti-CCP antibodies and immunoglobulin M-rheumatoid factor (IgM-RF), only MCP-1 levels were found to be significantly raised in patients with anti-CCP and IgM-RF compared with controls. CONCLUSION: Levels of MCP-1 were significantly increased in the plasma of patients having anti-CCP antibodies or IgM-RF and who later developed rheumatoid arthritis. These findings indicate up regulation of chemotactic activity for leucocytes before the development of rheumatoid arthritis.

Adult↗

PubMed1988

Immunohistology of rheumatoid nodules and rheumatoid synovium.

The immunohistological features of rheumatoid nodules and rheumatoid synovium were examined using monoclonal and polyclonal antibodies raised against macrophages, HLA-DR, leucocyte common antigen, and immunoglobulin components. The palisading cells surrounding the necrotic centre of the rheumatoid nodule were shown to be HLA-DR positive leucocytes, mostly histiocytes. The inflammatory infiltrate associated with rheumatoid nodules showed many immunohistochemical similarities to that of rheumatoid synovium, including a preponderance of IgG positive plasma cells, and a similar number and microanatomical pattern of distribution of HLA-DR positive cells. The significance of these findings for the cellular immunopathology and aetiology of the rheumatoid lesion is discussed.

Antigens, Differentiation↗

PubMed1990

Measurement of plasma concentrations of polymorphonuclear elastase-alpha 1 proteinase inhibitor (elastase-alpha 1 antitrypsin) in patients with rheumatoid arthritis: interference by rheumatoid factor.

The plasma concentration of granulocyte elastase in complex with alpha 1 proteinase inhibitor was determined in 32 patients with rheumatoid arthritis and eight with seronegative spondarthritis complicated by peripheral joint synovitis. Most patients had concentrations of complex which were within the range of the control group when measured by an 'in-house' enzyme linked immunosorbent assay, though several of the patients with rheumatoid arthritis had raised concentrations. When the complexes were measured by a commercially available assay, however, much higher values were obtained for many of the patients with rheumatoid arthritis. Evidence is presented indicating that the commercially available assay may suffer seriously from interference by rheumatoid factor. The possibility is discussed that most patients with rheumatoid arthritis may have plasma concentrations of elastase-alpha 1 PI which are normal or only slightly raised, and that previously published reports using assay systems similar to that available commercially might also have produced falsely raised values for many individuals with rheumatoid arthritis.

Adult↗

PubMed1990

Specificity of rheumatoid factors in relation to the disease state in rheumatoid arthritis.

Rheumatoid factors found in patients with rheumatoid arthritis react with human IgG and with IgG from some other species. The levels of rheumatoid factor give some indication of prognosis, albeit a rather poor one in this highly variable disease. The high degree of variability may, in part, be due to differences in the fine specificity of the rheumatoid factor in each individual patient, leading to differences in the types of immune complex formed. To study this hypothesis the fine specificity of rheumatoid factors of the IgM, IgA, and IgG classes for IgG from human, baboon, orangutan, macaque, owl monkey, gorilla, marmoset, cow, pig, sheep, goat, horse, mouse, and chicken was examined. Differential reactivity for these species was found and associations between the presence of rheumatoid factor and the development of moderate or severe erosions.

Animals↗

PubMedDate not supplied

[Levels of IgA rheumatoid factors in seropositive rheumatoid polyarthritis. Absence of correlation with disease activity or pejorative course].

Rheumatoid factors of the IgA isotype directed to human IgG Fc fragment were assayed, using an Elisa test, in the serum of 30 patients with seropositive rheumatoid arthritis and in the synovial fluid of 9 of them. A high incidence was found in the serum (90%) and synovial fluids (77%). Clinical, radiological and biological parameters of each patients were recorded at the time of the assay, and two years later. There was no statistically significant association between IgA rheumatoid factors levels and other parameters, nor with a pejorative evolution. However, a significant negative correlation was observed between IgA rheumatoid factors levels and the duration of the disease, suggesting that IgA rheumatoid factors are predominantly produced at the earliest stages of rheumatoid arthritis.

Adult↗

PubMedDate not supplied

[The experimental induction of rheumatoid factors of low affinity and cross reactivity with nonhistone nucleoproteins by means of anti-idiotypes directed at rheumatoid factors of high affinity and cross reactivity with histones H1 and H2b].

The study of the anti-nuclear cross reactivity of rheumatoid factors has shown differences between patients with rheumatoid arthritis and healthy seropositive subjects. This paper describes the finding, of a subpopulation of rheumatoid factor molecules which show a cross reactive idiotype and show high affinity for IgG and cross reactivity against histones in rheumatoid arthritis patients but not in healthy subjects. These molecules, in turn, were able to induce, experimentally, heterogeneous rheumatoid factor molecules that show a low affinity for IgG and cross-reactivity against nucleoproteins other than histones, most likely through idiotypic networks. The mechanism could be responsible for the diversification of serum autoantibodies found in rheumatoid arthritis.

Animals↗

PubMed1987

[Isotypes of rheumatoid factors and cellular immunity anomalies in rheumatoid polyarthritis. Apropos of 61 cases].

In 61 patients with rheumatoid polyarthritis, we studied the rheumatoid factors isotypes, class IgM, IgG, IgA and the abnormalities of the ratio CD4/CD8 (lymphocytes with membrane phenotype "helper"/lymphocytes with membrane phenotype "suppressor") determined by monoclonal antibodies. We found a statistically significant increase of the rate of IgM rheumatoid factors (p less than 0.0001), IgG (p less than 0.004), IgA (p less than 0.008), in patients with rheumatoid polyarthritis whose ratio exceeded that of the control population. On the other hand, the percentage of rheumatoid factors detected by agglutination was not significantly increased in this group. This increase seemed linked to a specific abnormality of the control of lymphocytes B which synthesize rheumatoid factors.

Adult↗

PubMed1983

[Rheumatoid factors: value of their determination in patients with rheumatoid arthritis].

IgM, IgA, IgG rheumatoid factors were investigated by a indirect immunofluorescence method in three groups of patients affected with rheumatoid arthritis of various picture: 30 patients with mild articular disease, 20 with severe joint involvement and 19 with articular and systemic symptoms. Rheumatoid factors occurred more frequently in patients with articular and extraarticular severe rheumatoid arthritis; moreover these patients showed higher titres and higher incidence of different immunoglobulin class rheumatoid factors in comparison with rheumatoid patients having mild joint disease.

Adolescent↗

PubMed1983

Local synthesis of IgM and IgM rheumatoid factor in rheumatoid pleuritis.

Pleura from 3 patients with rheumatoid pleuritis and from 5 patients with other diseases was examined for its capacity to synthesize IgM and IgM rheumatoid factor (RF). IgM was synthesized by pleura from all 3 patients with rheumatoid pleuritis and IgM RF by 2. Pleura from each of the control patients synthesized less than or equal to 1 ng/mg of IgM and IgM RF. Moreover, pleura from a 4th patient with rheumatoid pleuritis incorporated 3H-leucine into newly synthesized IgM. Simultaneously obtained pleural fluid mononuclear cells (MNL) and pleural tissue from a patient with rheumatoid pleuritis synthesized identical proportions of IgM and IgM RF whereas IgM RF production was not observed with peripheral blood MNL from the same patient. The results support the view that local production of IgM and IgM RF occurs in rheumatoid pleuritis and suggest that local immune events contribute to the pathogenesis of this disorder.

Arthritis, Rheumatoid↗

PubMed1995

How useful are tests for rheumatoid factors, antiperinuclear factors, antikeratin antibody, and the HLA DR4 antigen for the diagnosis of rheumatoid arthritis?

To evaluate the usefulness for the diagnosis of rheumatoid arthritis of tests for rheumatoid factors, antiperinuclear factors, antikeratin antibodies, and the HLA DR4 antigen, we retrospectively reviewed the medical records of 138 patients consecutively admitted to our rheumatology department between January 1, 1988 and December 31, 1990 for evaluation of peripheral inflammatory joint manifestations. Each patient had a standard work-up including a physical examination, laboratory tests, and roentgenograms. In 1994, after a follow-up of three to six years, the final diagnosis was rheumatoid arthritis in 39 patients and another well-defined disorder in 63; no diagnosis was established in 36 patients, among whom nine were lost to follow-up. The decreasing order of diagnostic usefulness was antiperinuclear factors, HLA DR4, rheumatoid factors (latex test), and antikeratin antibody. The likelihood of rheumatoid arthritis was greatest in those patients with positivity of two of the three following markers: rheumatoid factors, antiperinuclear factors, and the HLA DR4 antigen.

Adult↗

PubMed1964

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.

Adolescent↗

PubMed1989

Expression of the major rheumatoid factor cross-reactive idiotype in juvenile rheumatoid arthritis.

The major rheumatoid factor cross-reactive idiotype (RF-CRI), defined by prototypic monoclonal IgM rheumatoid factors, is expressed in high frequency by pokeweed mitogen-derived plasma cells from patients with rheumatoid arthritis who express RF in their sera. Unlike adults with rheumatoid arthritis, most patients with juvenile rheumatoid arthritis are seronegative for RF, as detected by classic IgG binding assays. We report that approximately 50% of seronegative patients with juvenile rheumatoid arthritis express the RF-CRI in high frequency among their pokeweed mitogen-derived plasma cells, and that approximately 33% of patients express the RF-CRI in high titer in their sera. The possible mechanisms for expression of an idiotypic marker of RF without expression of IgG binding activity by classic assays are discussed.

Adolescent↗

PubMed1994

A new model for rheumatoid arthritis generated by engraftment of rheumatoid synovial tissue and normal human cartilage into SCID mice.

OBJECTIVE: A new animal model was used to study the interaction between rheumatoid synovial cells and cartilage and to explore the cellular basis of rheumatoid joint destruction. METHODS: Fresh synovial tissue derived from patients with rheumatoid arthritis was implanted with normal human cartilage into SCID mice, either subcutaneously or under the renal capsule, for up to 304 days. The implants were analyzed by light and electron microscopy, as well as by immunohistochemistry and in situ hybridization. RESULTS: Human synovial tissue and cartilage implanted in SCID mice are maintained by the animals for up to 304 days. After 35 days, focal erosions occur at the site of attachment of synovial lining cells to the cartilage. After 105 days, a pannus-like formation, consisting of proliferating synovial fibroblast-like cells invading the cartilage, is observed. The fibroblast nature of these cells was supported by observation of only focal expression of the macrophage markers CD14 and CD68. Cells at the immediate site of cartilage destruction express messenger RNA for cathepsin L, whereas cathepsin D messenger RNA was detected in subsynovial regions away from the site of destruction. The human origin of the tissue involved in cartilage destruction was demonstrated using monoclonal antibodies to HLA-ABC and human type IV collagen. CONCLUSION: The present approach introduces a novel in vivo model of rheumatoid arthritis for the study of the molecular and cellular mechanisms of rheumatoid joint destruction at sites of synovial attachment to cartilage. In this model, the SCID mouse acts as a useful host for studying the properties of rheumatoid synovium in the absence of circulating human blood components.

Animals↗

PubMed1997

Methotrexate-associated appearance and rapid progression of rheumatoid nodules in systemic-onset juvenile rheumatoid arthritis.

Rheumatoid nodules are a rare extraarticular manifestation of juvenile rheumatoid arthritis (JRA), usually detected in patients with polyarticular-onset disease and positive rheumatoid factor (RF). To date, there has not been a published report of rheumatoid nodules in systemic-onset JRA. Low-dose methotrexate (MTX) is generally considered to be the most useful second-line drug in the treatment of polyarticular JRA. In adult RA, MTX has been shown to be associated with appearance and progression of rheumatoid nodules. This report describes a 3-year-old girl with RF-negative, antinuclear antibody-negative systemic JRA who developed multiple rheumatoid nodules on the scalp and trunk during MTX therapy. The first nodule developed on the scalp 6 months after MTX treatment was initiated. Previous treatment with azathioprine was not associated with nodulosis. This represents an atypical case of MTX-associated accelerated nodulosis in systemic JRA, and raises the problem of treatment plan modification in the presence of this side effect.

Antirheumatic Agents↗

PubMed2004

Lack of association of the HLA-DRB1 shared epitope with rheumatoid nodules: an individual patient data meta-analysis of 3,272 Caucasian patients with rheumatoid arthritis.

OBJECTIVE: The objective of this individual patient data (IPD) meta-analysis was to examine the relationship of rheumatoid nodules to the HLA-DRB1 shared epitope (SE) and to individual SE genotypes. METHODS: English-language studies that enrolled adult non-Hispanic Caucasian patients with rheumatoid arthritis (RA) were identified by searches of Medline and Embase, and by manual searches of medical journals. All authors were contacted for IPD. Meta-analysis was performed to assess the association of SE presence, dose, and genotype with rheumatoid nodules. Meta-analyses adjusted for disease duration and cumulative meta-analyses were also performed to assess the influence of RA duration and year of study publication on the results. RESULTS: A total of 24 studies and 3,272 patients were available for analysis. IPD were obtained for 22 of the studies. There was a nonsignificant association between the presence of the SE (i.e., 1 or 2 alleles versus 0 alleles) and rheumatoid nodules (summary odds ratio [OR] 1.3, 95% confidence interval [95% CI] 0.97-1.6). Analysis by SE genotype, however, demonstrated a weak relationship with inheritance of a single DRB1*0401 SE allele (OR 1.4, 95% CI 1.1-1.8). No other genotypes achieved statistical significance in the adjusted or unadjusted analyses. CONCLUSION: The presence of the HLA-DRB1 SE does not appear to significantly increase the risk of rheumatoid nodules among Caucasian patients with RA. Analysis by DRB1 SE genotype was uninformative, suggesting only a potential (and at most modest) role of the DRB1*0401 SE allele. Results from this IPD meta-analysis implicate other genetic, stochastic, and/or environmental factors in the susceptibility to rheumatoid nodules.

Aged↗

PubMed1979

Viruses and lymphocytes in rheumatoid arthritis. II. Examination of lymphocytes and sera from patients with rheumatoid arthritis for evidence of retrovirus infection.

The possible involvement of retroviruses in the aetiology of rheumatoid arthritis (RA) was investigated. Retrovirus antigens were not expressed on rheumatoid synovial and peripheral blood lymphocytes as judged by membrane immunofluorescence, radioimmunoassay, and complement-mediated cytotoxicity. The specific antiretroviral (anti-RD-144 and anti-SSAV) sera used in this study were produced in rabbits immunised with viral antigens grown in a homologous system (rabbit cells and medium supplemented with normal rabbit serum), avoiding non-specific immunofluorescence previously detected with donated antiretroviral sera. Immune complexes lodged in the rheumatoid synovial membranes did not contain, and other cells within the membranes did not express, retroviral antigens. Antibodies cross-reacting with primate retrovirus antigens were sought in sera from patients with 'autoimmune' diseases by means of solid phase radioimmunoassay. There were no retrovirus antibodies in the 3 groups of patients studied, that is, those with rheumatoid arthritis, systemic lupus erythematosus, and with non-RA conditions. Absorption of rheumatoid factor did not alter this conclusion. These results give little support to the hypothesis that activation of endogenous human retroviruses or an infection with horizontally transmitted retroviruses is associated with the rheumatoid process.

Antigens, Surface↗

PubMed1982

Superficial ulcerating necrobiosis in rheumatoid arthritis. A variant of the necrobiosis lipoidica-rheumatoid nodule spectrum?

Although necrobiosis is not a precise term, it primarily refers to collagen changes found in association with the palisading granulomas seen in granuloma annulare, necrobiosis lipoidica diabeticorum (NLD), and rheumatoid nodules. While the pathogenesis of each of these conditions remains unknown, immune complex vasculitis and delayed hypersensitivity mechanisms have been postulated. Two patients are described, having "classic" rheumatoid arthritis with chronic, superficial, ulcerating, discrete lesions on their lower legs that histologically were interpreted as NLD. While the argument for a chance association of NLD and rheumatoid arthritis could be advanced, the occurrence of identical lesions in two patients with high-titer rheumatoid factor, rheumatoid nodules, and some clinical and microscopic evidence of a low-grade rheumatoid vasculitis suggests a new subset of patients with necrobiotic palisading granulomas.

Aged↗

PubMed2000

Balneotherapy for rheumatoid arthritis and osteoarthritis.

BACKGROUND: Balneotherapy (hydrotherapy or spa therapy) for patients with arthritis is one of the oldest forms of therapy. One of the aims of balneotherapy is to soothe the pain and as a consequence to relieve patients' suffering and make them feel well. OBJECTIVES: To perform a systematic review to assess the effects of balneotherapy for rheumatoid arthritis and osteoarthritis. SEARCH STRATEGY: Using the Cochrane search strategy, studies were found by screening: 1) The Medline CD-ROM database from 1966 to June 1999 and 2) the database from the Cochrane Field 'Rehabilitation and Related Therapies', which contains also studies published in journals not covered by Medline. Also, 3) reference checking and 4) personal communications with authors was carried out to retrieve eligible studies. To perform an adequate assessment of the methodological quality the languages of the publications had to be: Dutch, English, French or German. Date of the most recent literature search: June, 1999 SELECTION CRITERIA: Studies were eligible if they were randomized controlled trials (RCT) comparing balneotherapy with any intervention or with no intervention. Patients included had rheumatoid arthritis (RA), osteoarthritis (OA) or some other form of arthritis. Trials incorporating patients with definite or classical rheumatoid arthritis (RA) as defined by the American Rheumatism Association Criteria (ARA) (Ropes 1958) (these criteria have changed over time) or by the criteria of Steinbrocker (1949) were regarded as a separate group. At least one of the WHO/ILAR core set of endpoints for RA clinical trials had to be the main outcome measures. DATA COLLECTION AND ANALYSIS: A criteria list used to assess the methodological quality was the one developed at the Department of Epidemiology at the Maastricht University, called "the Maastricht list". The quality scores and data abstraction of the studies were carried out independently by two reviewers (HdV, RdB). Disagreements were solved by consensus. MAIN RESULTS: Ten trials with 607 patients were included in this review. Most trials reported positive findings, but were methodologically flawed to some extent. A 'quality of life' outcome was reported by two trials. Just one of the randomized trials mentioned an intention-to-treat analysis and only three performed a comparison of effects between groups. Pooling of the data was not performed, because of heterogeneity of the studies, multiple outcome measurements, and, apart from two studies, the overall data presentation was too scarce to enable pooling of the data. REVIEWER'S CONCLUSIONS: One cannot ignore the positive findings reported in most trials. However the scientific evidence is weak because of the poor methodological quality, the absence of an adequate statistical analysis, and the absence, for the patient, of most essential outcome measures (pain, quality of life), Therefore, the noted "positive findings" should be viewed with caution. Because of the methodological flaws an answer about the efficacy of balneotherapy cannot be provided at this time. Flaws found in the reviewed studies could be avoided in future trials.

Arthritis, Rheumatoid↗