In vitro synthesis of IgM and IgM rheumatoid factor in seronegative arthritides

Summary In vitro patterns of IgM and IgM rheumatoid factor (RF) synthesis exhibited by peripheral blood B cells (MNL) obtained from healthy individuals as well as patients with seropositive and seronegative rheumatoid arthritis (RA) have been previously examined. The present study was performed in a group of patients with non-rheumatoid seronegative arthritis (SNA) in order to compare patterns of in vitro IgM and IgM RF synthesis to that previously observed with seropositive and seronegative RA. Eighteen patients with SNA (4 ankylosing spondylitis, 10 psoriatic arthritis, and 4 unclassified variant disease) were studied as well as 18 healthy adult controls.Spontaneous release of IgM RF by MNL was not observed in SNA or controls. In contrast, IgM RF was detected in pokeweed mitogen (PWM)-stimulated MNL culture supernatants from 9/18 SNA (mean±SD=17.0±9.9 ng/10⁶ cells), and 10/18 normal controls (16.7±9.9 ng). Synthesis of IgM by PWM-stimulated MNL from SNA (2 062±1 200 ng) was significantly less than observed with MNL from controls (4 093±1 896 ng) (P<0.001). There were no differences among the various SNA subsets with regards to the levels of IgM and IgM RF produced either spontaneously or after PWM stimulation. IgM RF constituted a small fraction of the total IgM in SNA and normals (0.9% and 0.5%, respectively). This is clearly distinct from seropositive RA in which we have previously established that IgM RF constitutes a substantial fraction of the total IgM (10.7%) (P<0.01). IgM and IgM RF production did not appear to be significantly influenced by immunosuppressive medication.The results suggest that regulatory mechanisms governing the expression of RF are intact in patients with SNA and that lack of in vivo RF production in these patients cannot be related to an absolute deficiency of PWM-inducible mature RF committed B cells.     

Significance of rheumatoid factor isotypes in seronegative rheumatoid arthritis

Summary In a cross-sectional study of 124 patients with definite or classical rheumatoid arthritis (RA) and negative agglutination assays, rheumatoid factor (RF) isotypes were measured using an ELISA technique. Elevated levels of IgA-RF were found in 55 patients (44%), IgG-RF in 99 (80%), and IgM-RF in 20 (16%). The levels of IgA- and IgM-RF correlated with each other (P<0.001). Elevated levels of IgM-RF were associated with a more severe disease course. Elevated levels of IgA-RF correlated with the occurrence of bone erosions. The results of this study suggest that in patients with RA and negative agglutination assays, both IgM- and IgA-RF are markers of disease severity.     

Complement-activating properties of IgM rheumatoid factors reacting with IgG subclasses

Summary To estimate the complement-activating property (CAP) of IgM rheumatoid factor (RF), which was purified from synovial fluids of patients with rheumatoid arthritis, in a reaction with each IgG subclass, the activation and binding of C4 in the classical pathway of complement by IgM RF was measured in an enzyme-linked immunosorbent assay using biotinylated F(ab')₂ antibody to human C4. The CAP of IgM RF reacting with IgG3 was significantly higher than that of IgM RFs bound to the other IgG subclasses (P<0.01). These results suggest that IgM RF reacting with IgG3 in synovial fluid could induce a greater degree of complement-dependent inflammation in RA synovium than IgM RF reacting with other IgG subclasses.     

A comparison of patients with seropositive and seronegative rheumatoid arthritis

Summary It has recently been suggested that a subpopulation of patients with rheumatoid arthritis, diagnosed on clinical, radiologic and pragmatic grounds, but with negative rheumatoid factor tests, represents a clinical entity quite distinct from that of seropositve rheumatoid arthritis. We have studied 60 sequentially presenting patients, 30 of whom were selected because they were seronegative, and 30 selected because they were seropositive in regard to IGM rheumatoid factor. The only major differences detected between the two groups on blind assessment were a greater tendency to deformity, a greater degree of erosion and the presence of subcutaneous nodules in the seropositive group. Seronegative and seropositive rheumatoid arthritis appear to have very similar clinical features, but differing degrees of severity.     

Rheumatoid nodulosis: A puzzling variant of rheumatoid arthritis

Summary Four patients with rheumatoid nodulosis are here described, together with a review of cases reported to date in the literature. This particular variant of rheumatoid arthritis (RA) is characterized by the presence of subcutaneous rheumatoid nodules, scanty or absent systemic manifestations and a clinically benign course. Joint involvement appears more commonly as palindromic rheumatism, although patients with arthralgia episodes alone and others with chronic polyarthritis have been described. Seldom reported up to now, a consideration of this entity may help to avoid diagnostic pitfalls and the use of aggressive therapy.     

Rheumatoid nodules indicating seronegative rheumatoid arthritis in a patient with gout

 The association of gout and rheumatoid arthritis is rare. We report the case of a patient with gout who presented with rheumatoid nodules indicating seronegative rheumatoid arthritis. Received: 29 July 2002 / Accepted: 4 November 2002     

A double-blind controlled study comparing sulphasalazine with placebo in rheumatoid factor (RF)-negative rheumatoid arthritis

Summary The efficacy and tolerability of sulphasalazine (SASP) was examined in a double blind, placebo-controlled 24-week study of 32 patients with rheumatoid factor (RF)-negative RA. Twelve patients (75%) of the SASP group completed the study; 4 patients were withdrawn because of an adverse event. Ten patients (62.5%) in the placebo group completed the study; 5 dropped out because of lack of response and one because of an adverse reaction.Efficacy was demonstrated by a significant and sustained improvement in the indices of disease activity in the SASP group. It was confirmed by significant intergroup differences in favour of SASP over placebo in the changes in ESR, Ritchie index, number of painful joints and clinical score. There was also a significant difference in favour of SASP in the number of responders and the number of withdrawals due to inefficacy. The character, frequency and timing of side-effects were similar to those previously reported. All were reversible on stopping therapy.This study shows that SASP is an effective second-line drug for treating patients with RF-negative RA.     

HLA typing and seropositivity in finnish and in polish patients with rheumatoid arthritis and amyloidosis

Summary We determined HLA-A,-B,-C and-DR antigens in 83 patients with rheumatoid arthritis (RA) and reactive secondary amyloidosis (RSA), 60 in Finland and 23 in Poland, and compared the results with control RA patients and blood donors. There were no significant differences in the frequencies of HLA between the RA patients with and those without RSA in either Finland or Poland, and no significant differences between the Finnish and Polish patients with RSA. All the RSA patients from Finland and 70% of the RSA patients from Poland were seropositive. In the development of RSA, the prolonged period of inflammatory stimuli may play a more important role than genetic factors.     

A clinical and biochemical assessment of etidronate disodium in patients with active rheumatoid arthritis

Summary Diphosphonates reduce the rate of bone turnover. They have additional pharmacological properties improving adjuvant arthritis in rats and lowering ESR in this condition. We have evaluated etidronate disodium, a diphosphonate commonly prescribed in the United Kingdom for Paget's disease in patients with rheumatoid arthritis. Apart from an early improvement in articular index, perhaps reflecting anti-inflammatory activity, no significant change occurred in clinical variables or in laboratory indices of secondline action at a dose of 5 mg/kg/day.     

Serum osteocalcin as an index of bone turnover in active rheumatoid arthritis and in active psoriatic arthritis

Summary Juxtaarticular osteoporosis is a recognized clinical feature in both rheumatoid arthritis (RA) and psoriatic arthritis (PA), while generalised osteopenia seems to be characteristic of RA only. To assess differences in bone turnover in the two forms of disease, we measured serum osteocalcin levels and other parameters of bone metabolism in two groups of female, ambulant, age-matched patients suffering from active RA or active PA and never treated with steroid therapy. Serum osteocalcin levels were significantly higher in RA patients than in PA patients (13.05±1.27 ng/ml vs 4.83±0.88 ng/ml;p<0.001), with a significant positive correlation between osteocalcin and serum alkaline phosphatase in both groups. These data suggest that bone turnover is higher in active RA than in active PA. Juxtaarticular osteoporosis could be mediated by local disease mechanisms both in RA and in PA, while factors specifically related to active RA seem to determine a more generalized impairment of bone turnover.     

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目的探讨类风湿关节炎(RA)患者中贫血的发生率、严重程度及其与RA病情活动及治疗间的关系。方法对2002-07-2004-04在北京大学人民医院风湿免疫科住院的239例类风湿关节炎患者进行回顾性分析。结果(1)RA患者中贫血的发生率为51.4%,伴发贫血的程度为轻、中度的贫血;(2)RA贫血组患者和RA不伴发贫血组患者在病程、晨僵、血沉、C反应蛋白、双手X线分级方面的差异有显著性。(3)RA贫血患者和RA不伴发贫血患者在白细胞计数及血小板计数方面差异有显著性。(4)RA贫血患者住院前后的Hb水平存在显著性差异。结论(1)贫血是RA最常见的关节外表现之一,伴发贫血程度为轻、中度贫血。(2)RA伴发的贫血与病情活动性相关,病情活动性越高,贫血程度越重;并且贫血程度越重者,关节破坏越重,病情预后差。(3)RA贫血患者的血红蛋白水平可以随着抗风湿治疗后RA病情的好转而上升。     

IgM,IgA and IgG rheumatoid factors in patients with rheumatoid arthritis and normal donors

Summary IgM, IgA, and IgG Rheumatoid Factors (RF) were measured by ELISA assay in serum from 26 patients with definite rheumatoid arthritis (RA) and 11 normal controls. IgM-RF was assayed by ELISA, radioimmunoassay,and also by the standard latex fixation test in all sera from RA patients. In patients with RA quantitative amounts of IgM, IgA, and IgG-RF as estimated by ELISA were highly correlated. Significant correlations were found between a physician's rating of disease activity and IgG-RF (r=0.44; p<.02) and IgA-RF (r=0.38; p=.06 but not for IgM-RF as measured in any of the three assays.During the course of this work F.S. was supported by a NATO fellowship from the Consiglio Nazionale delle Ricerche, Roma, Italy.     

Rheumatoid nodules do not predict response to treatment with slow-acting anti-rheumatic drugs

Summary Rheumatoid nodules have been associated with a poor long-term prognosis. We investigated whether they predict a poor response to treatment with slow-acting anti-rheumatic drugs (SAARDs). Two hundred and twenty-eight patients with rheumatoid arthritis (RA) were treated for six months with a SAARD. Clinical and laboratory assessments of disease activity were made initially and after 6 months' treatment. Patients were divided into two groups according to the presence or absence of nodules at entry. Twenty-one % had nodules before treatment but their response was no different to patients without nodules (79%), both groups showing improvements in all variables. Males were more likely to develop nodules and had a relative risk of 1.7. High titres of rheumatoid factor correlated with nodules and no sero-negative patients had nodules. We conclude that nodules are not predictive of poor response to treatment with a SAARD, despite their presence being associated with a poor long-term prognosis. One possible implication is that SAARDs themselves, despite an early response, may not effect long-term outcome.     

Tumour necrosis factor alpha and interleukin-2 in plasma from rheumatoid arthritis patients in relation to disease activity

Summary Tumour necrosis factor alpha (TNF) and interleukin-2 (IL-2) are potential immunological mediators of pathogenetic changes in rheumatoid arthritis. We measured the concentrations of TNF and IL-2 in plasma from 2 groups of patients suffering from rheumatoid arthritis (RA). One group had high and one had low disease activity. In addition, in connection with steroid treatment in the high disease activity group, TNF was significantly increased in plasma from RA patients with high disease activity compared with those of low disease activity (p=0.0009). Furthermore, TNF decreased significantly in relation to steroid medication, parallel to clinical improvement (p=0.016). All IL-2 concentration measurements were within the estimated normal range. The increased TNF plasma levels in patients with rheumatoid arthritis with high disease activity, might result from activated white mononuclear cells in the inflamed joints. This might, in part, support the theory that TNF is a possible mediator of pathogenetic changes known to occur in rheumatoid arthritis.     

Rheumatoid arthritis associated with ankylosing spondylitis defined by scintigraphic and CT abnormalities

Summary Rheumatoid arthritis and ankylosing spondylitis were detected in the same patient after a long period of observation of the disease. X-ray studies demonstrated the characteristic rheumatoid arthritis changes in peripheral joints. By contrast, few X-ray changes of ankylosing spondylitis were detected, during follow-up. Diagnostic approach through scintigraphic studies disclosed a symmetric uptake of the radionuclide in sacroiliac joints, and computed tomography revealed bilateral ankylosis. The combination of these tests was useful to define the presence of axial disease. This patient was both HLA B27 and DR4 positive. Rheumatoid arthritis occurred before ankylosing spondylitis, that interestingly was defined as a late onset disease.     

Acute rheumatoid factor positive (IgM) polyarthritis associated with a klebsiella pneumonitis

Summary The authors report a case of a patient suffering from acute polyarthritis with a high rheumatoid factor titre, associated with a Klebsiella pneumonitis. A polyclonal B lymphocyte activation or a possible cross reaction between rheumatoid factor and an antigen related to Klebsiella may explain the elevated production of rheumatoid factor observed.     

Spontaneous and aggregated IgG induced rheumatoid factor producing cells in rheumatoid arthritis

Summary Seropositive rheumatoid arthritis (RA) patients were found to have high numbers of spontaneously occurring cells making rheumatoid factor (RF) reactive with human IgG as measured by a RF plaque forming cell (RF-PFC) assay. There was a significant positive correlation between the number of RF-PFC and both disease activity measured by the sedimentation rate and RF titer measured by the RA latex test. Aggregated IgG and pokeweed mitogen were equally effective stimulators of RF-PFC in cultures of RA peripheral blood mononuclear leukocytes. The rheumatoid ratio of helper (T4): suppressor (T8) T lymphocytes was also significantly increased over the ratio of normal controls, but this ratio did not correlate with the number of RF-PFC. Aggregated IgG or immune complexes may be responsible for stimulating RA RF-PFC in vivo.     

Food allergy in patients with rheumatoid arthritis

Summary Three hundred patients of the Swiss Rheumatoid Arthritis Patient Union were asked by questionnaire whether they had any adverse reaction from food. Of the 159 replies 52 gave a positive history. Thirty-five patients could be further evaluated. Six patients, who gave the mose typical history of allergy, were investigated clinically, with laboratory tests and technetium-scintigramme after food challenge. There was no sign of an immunologic reaction in any of the measured parameters. The other patients were interviewed a second time with an extensive allergological questionnaire. None of the food intolerances could be substantiated.     

Hidden psoriatic arthritis in seronegative oligoarthritis: A 14-year follow-up study

Summary Out of a cohort of 64 patients with seronegative oligoarthritis (SO), 8 patients with HLA-B13, 5 with Bw16 and 3 with HLA-B17 were invited to participate in a 14-year check-up. Thirteen patients showed some features of psoriatic arthritis, including 5 with suspected skin or nail disease, 5 with a family history of psoriasis, 3 with DIP joint affliction, and 2 with aortic valve insufficiency. It is concluded that a quarter of the patients with SO may have hidden psoriatic arthritis.     

Complement-fixing hidden rheumatoid factor in children with benign rheumatoid nodules

Rheumatoid nodules have been described in many children without evidence of clinical disease. These have been referred to as benign rheumatoid nodules (BRN). Except for one report, no serological abnormalities have been demonstrated. Four children with BRN have been studied. By means of a hemolytic assay, high titers of hidden rheumatoid factor (RF) have been found in the blood, i.e., 19S IgM RF detected after acid separation of IgM-containing fraction from the serum. The median hidden RF titer of the children with BRN was 1:362 and in healthy and disease controls was 1:7. The difference was significant at P < 0.001. The results indicate that patients with BRN have active complement-fixing 19S IgM RF in their serum. Thus, the association of hidden RF with BRN raises the possibility that the deposition of immune complexes (19S IgM-7S IgG) leads to small vessel vasculitis and nodular formation.