Intensity of the production of rheumatoid factor in patients with different degrees of sensitization to Borrelia garinii antigens

The content of rheumatoid factor and the levels of IgA, IgM, IgG in patients with different degrees of sensitization to Borrelia garinii antigens were studied. The titer of rheumatoid factor was found to increase in accordance with the growth of the levels of anti-Borrelia antibodies. A rise in the concentration of serum immunoglobulins simultaneously with the development of Borrelia infection was registered. The mechanisms of autoimmunization are discussed, taking into account the known biological properties of the causative agent of Lyme disease.     

Determination of the rheumatoid factor in gouty patients

The authors have examined the incidence of the rheumatoid factor in the serum of a group of 100 patients, 95 males and 5 females, suffering from gout, of whom only 6 suffered from chronic gout. The rheumatoid factor in the serum was measured by RA-test (1:40) and by Waaler-Rose test (1:32). The rheumatoid factor was not present in the examined subjects and so we can state that such serum parameter does not represent, for its negativity, a laboratory index of any evidence in the gout and it doesn't represent a reason for diagnostic doubts with other forms with the rheumatoid factor in the serum.     

Radioimmunoassay of IgG and IgM rheumatoid factors reacting with human IgG.

Although IgG rheumatoid factor may play a central role in the pathogenesis of rheumatoid arthritis, previously there have been no precise methods for its specific measurement in serum and synovial fluid. This paper describes a solid phase radioimmunoassay for the independent quantification of IgM and IgG rheumatoid factor reacting with the Fc fragment of human IgG. As measured by this assay, serum IgG rheumatoid factor levels differed significantly between patients with seropositive and seronegative rheumatoid arthritis and normal control subjects. In addition, several sera and joint fluids from patients with seropositive rheumatoid arthritis, even without vasculitis, were shown by gel chromatography to have acid-dissociable complexes of IgG rheumatoid factor suggestive of IgG-IgG dimer or trimer formation.     

Copper chelation with tetrathiomolybdate suppresses adjuvant-induced arthritis and inflammation-associated cachexia in rats

Tetrathiomolybdate (TM), a drug developed for Wilson's disease, produces an anti-angiogenic and anti-inflammatory effect by reducing systemic copper levels. TM therapy has proved effective in inhibiting the growth of tumors in animal tumor models and in cancer patients. We have hypothesized that TM may be used for the therapy of rheumatoid arthritis and have examined the efficacy of TM on adjuvant-induced arthritis in the rat, which is a model of acute inflammatory arthritis and inflammatory cachexia. TM delayed the onset of and suppressed the severity of clinical arthritis on both paw volume and the arthritis score. Histological examination demonstrated that TM significantly reduces the synovial hyperplasia and inflammatory cell invasion in joint tissues. Interestingly, TM can inhibit the expression of vascular endothelial growth factor in serum synovial tissues, especially in endothelial cells and macrophages. Moreover, the extent of pannus formation, which leads to bone destruction, is correlated with the content of vascular endothelial growth factor in the serum. There was no mortality in TM-treated rat abnormalities. TM also suppressed inflammatory cachexia. We suggest that copper deficiency induced by TM is a potent approach both to inhibit the progression of rheumatoid arthritis with minimal adverse effects and to improve the well-being of rheumatoid arthritis patients.     

Modifications in alpha 2 globulins, gamma globulins and in rheumatoid factor during gold salt therapy in rheumatoid arthritis]

A total dose of g 1.071, given as hydrosoluble salts for a 12 month period, showed a significant decrease in serum gamma globulins along with clinical improvement in 17 patients affected with rheumatoid arthritis. A decrease in alpha 2 globulins and in rheumatoid factor titre was observed too, but it was not significant. The data suggest that in rheumatoid arthritis the gold therapy might also be effective on the immunological disease mechanism.     

Onset,Early Stages,and Prognosis of Rheumatoid Arthritis: A Clinical Study of 100 Patients with 11-year Follow-up

One hundred patients with “definite” or “classical” rheumatoid arthritis were followed in a hospital clinic from within one year of the onset of the arthritis. The average interval between onset and first attendance was 3·7 months. Onset was commoner in the winter, transient prodromal symptoms being noted in 23, with possible precipitating factors in 14. The serum rheumatoid factor test was positive at some time in 88.The patients were reassessed between eight and 14 years later. Seventeen died during this period, five possibly as a result of the disease or its treatment.The remaining patients had improved as a whole in terms of the blood sedimentation rate, haemoglobin, titre of the rheumatoid factor test, and status of the disease, but there was an overall deterioration in functional capacity. Both the rheumatoid factor titre and the functional capacity at an earlier review could be directly correlated with the outcome, but other factors were not found to influence the ultimate prognosis.     

Anti-idiotypic antibodies in a patient with monoclonal rheumatoid factor after pneumococcal bacteremia

A 51-yr-old Japanese female patient with monoclonal IgM gammopathy with rheumatoid factor activity was admitted because of pneumococcal bacteremia. About 2 wk after admission, her rheumatoid factor activity became undetectable by RAHA test and radioimmunoassay, subsequent to the initial marked elevation. The suppressive capacity of the patient's IgG fraction on the rheumatoid activity of her monoclonal IgM on January 11 was determined. The IgG fraction obtained on February 22 blocked the binding of the rheumatoid factor to rabbit IgG. The suppressive activity in the IgG fraction of February 22 was shown to be localized within the F(ab')2 fragment. Furthermore, the specificity of the suppressive serum factor was shown by the inability to block the binding of SRBC coupled with diazotized phosphorylcholine to anti-pneumococcal antibody. Thus, the marked reduction of rheumatoid factor activity was considered to result from anti-idiotypic antibody transiently appearing in her serum after pneumococcal bacteremia.     

Controlled activation of the Cpx system is essential for growth of Yersinia enterocolitica

Until recently, three spirochete genospecies were considered to be the causative agents of Lyme borreliosis (LB) in Europe: Borrelia burgdorferi sensu stricto, Borrelia afzelii and Borrelia garinii . However, the DNA of Borrelia valaisiana, Borrelia lusitaniae, Borrelia spielmanii and Borrelia bissettii has already been detected in samples of human origin, or the spirochetes were isolated from the patients with symptoms of LB. Molecular analysis of 12 selected serum samples collected in the regional hospital confirmed the presence of B. bissettii DNA in cases of single and multiple infection in patients with symptomatic borreliosis or chronic borrelial infection. The presence of B. bissettii as a single strain in patients provides strong support of the fact that B. bissettii might be a causative agent of the disease. After the first isolation of B. bissettii from the samples of human origin in Slovenia, following the detection of this species in cardiac valve tissue of the patient with endocarditis and aortic valve stenosis in the Czech Republic, here we present additional molecular data supporting the involvement of B. bissettii in LB in Europe.     

A comparison of euglobulin fractions and whole serum in the hemagglutination and latex fixation tests

One hundred and thirty-two sera were investigated with the Waaler-Rose and latex fixation reactions. The reactions were performed with serum, with acid-precipitated euglobulin, and with cold-precipitated euglobulin. The material consisted of 35 sera from healthy persons, 23 from patients with various diseases, 28 from patients with joint symptoms not due to rheumatoid arthritis, and 46 from patients with classical rheumatoid arthritis.In rheumatoid arthritis sera, an increase in positive reactions was obtained in the Waaler-Rose test from 70 per cent in serum to 83 per cent in acid-precipitated euglobulin. This increase was due to a greater specificity of reactions with low titers. The cold-precipitated euglobulin gave less positive Waaler-Rose reactions than the acid-precipitated euglobulin. With the latex fixation test an increase from 65 per cent positive reactions in serum to about 71 per cent with both cold- and acid-precipitated euglobulin fractions was obtained. Here, the increase consisted of reactions negative in serum but positive in the euglobulin fractions, but again with low titers. Because the increase in positive reactions consists merely of low titer values, fractionation of sera only slightly enhances the reliability of the serological tests.Negatively reacting rheumatoid arthritis sera often had low values of the _2A globulin.     

Comparison of Antibody Titers against Borrelial Strains Isolated in Japan by the Microcapsule Agglutination Test for Serological Studies of Early Lyme Disease

Results of a passive microcapsule agglutination test using 2 Japanese strains, Borrelia garinii and Borrelia afzelii, were comparable to that of the passive microcapsule agglutination test using a Swiss strain Borrelia burgdorferi IRS in detecting antibodies of an early stage of Lyme disease patients in Japan. MCAT with microcapsule sensitized strain IRS seems likely to become one of the important tools for the early diagnosis of Lyme disease in the world. The highest titer of MCAT was detected in the serum samples of patients which were taken around 2 weeks after erythema chronicum migrans. The test is very simple and can be employed easily in diagnostic laboratories.     

塞来昔布治疗类风湿性关节炎的临床疗效及其对血清CRP、RF水平的影响

目的:研究塞来昔布治疗类风湿性关节炎的临床评价及其对患者血清C反应蛋白(CRP)、类风湿因子(RF)水平的影响。方法:选取2014年9月至2015年8月本院收治的84例类风湿关节炎患者,按照随机数字法分为观察组和对照组,每组42例。对照组采取常规方案进行治疗,观察组患者在对照组治疗基础上加以塞来昔布进行治疗。比较两组患者治疗前和治疗后CRP、RF、白介素-1(IL-1)、白介素-6(IL-6)水平的变化、临床疗效和不良反应的发生情况。结果:治疗后,观察组患者的总有效率、患者的自评疗效总有效率均显著高于对照组(P0.05)。治疗前,两组患者血清CRP、RF、IL-1、IL-1、IL-6水平比较差异无统计学意义(P0.05);治疗后,两组患者血清CRP、RF、IL-1、IL-1、IL-6水平均较治疗前显著降低(P0.05),且观察组的血清CRP、RF、IL-1、IL-1、IL-6水平显著低于对照组(P0.05)。此外,观察组的不良反应率显著低于对照组(P0.05)。结论:塞来昔布能显著提高类风湿性关节炎患者的临床疗效,且安全性较高,可能与其有效降低血清CRP、RF水平有关。     

Rheumatoid arthritis: relation of serum C-reactive protein and erythrocyte sedimentation rates to radiographic changes.

Serum C reactive protein (CRP) levels and erythrocyte sedimentation rates (ESR) were measured in 56 patients with rheumatoid arthritis. Radiographical damage, based on a count of erosions, was significantly more likely to occur when serum CRP and ESR were persistently raised, irrespective of the presence or absence of rheumatoid factor. Measurements of both CRP and ESR were more helpful than either alone, but CRP was probably the more informative. Serial measurements of CRP and ESR provide a reliable means of discriminating between drugs that provide symptomatic relief only and those with a more profound effect in rheumatoid arthritis.     

Anti-keratin antibodies in rheumatoid arthritis.

A naturally occurring antibody that reacts with the keratinised tissue of animal oesophagus was found in the serum of 75 out of 129 patients (58%) with classical or definite rheumatoid arthritis (RA) but not in sera from 105 healthy people. Detection of the antibody, which is unrelated to rheumatoid factor, is more specific for RA than the reaction in the sheep-cell agglutination test but less sensitive.     

Immune-Mediated Fever in the Dog. Occurrence of Antinuclear Antibodies, Rheumatoid Factor, Tumor Necrosis Factor and Interleukin-6 in Serum

Contents of antinuclear antibodies (ANA), rheumatoid factor (RF), tumor necrosis factor (TNF-α) and interleukin-6 (IL-6) were measured in serum from 20 dogs with immune-mediated fever. Seven out of 20 patients were ANA positive, 1 out of 20 was positive to antibodies against extractable nuclear antigens (ENA), 1 out of 20 was positive to antibodies against deoxynucleoproteins (DNP), 2 out of 13 were RF positive and none out of 20 patients had antibodies against native DNA in the serum. TNF-α was not detected in any serum of 15 dogs with immune-mediated fever, while 10 out of 13 presented with elevated IL-6. The results varied between patients, but the IL-6 level was high in most of them. This indicate a role for IL-6 in the pathogenesis of immune-mediated fever in most cases.     

Nature of double-stranded DNA binding activity in seropositive rheumatoid arthritis: formation of low avidity DNA/rheumatoid factor/IgG/low density lipoprotein complexes

Sera from majority of patients with seropositive rheumatoid arthritis, which generally lacked detectable anti-double stranded DNA in Farr, Crithidia luciliae, and microcomplement fixation assays, exhibited high levels of dsDNA binding in the presence of 3.5% polyethylene glycol when using intrinsically labeled 3H-PM2 DNA as antigen. Except for SLE, such increased dsDNA binding was absent in normal and a variety of other disease sera, including those from patients with seronegative rheumatoid arthritis. In contrast to the situation in SLE, in which dsDNA binding is mediated by specific anti-DNA antibody, the increased dsDNA binding activity in seropositive rheumatoid arthritis was shown to be dependent upon complex low avidity interactions involving DNA, IgG, IgM rheumatoid factor, and low density lipoproteins. Analysis of the composition of the polyethylene glycol serum precipitates by 2-dimensional gel diffusion, immunoelectrophoresis, and sodium dodecyl sulfate polyacrylamide gel electrophoresis failed to reveal the presence of additional DNA-binding proteins unique to seropositive rheumatoid arthritis. The only feature distinguishing high DNA binding sera from those with low DNA binding activity was an increased amount of polyethylene glycol-insoluble IgG in the former, presumably reflecting IgG/IgG and/or IgG/IgM complexes. The significance of these unusual DNA/low density lipoprotein/IgG/rheumatoid factor complexes with respect to the diagnostic specificity and pathophysiology of the DNA/anti-DNA system is discussed.     

Selection of a Borrelia burgdorferi antigenic variant by cultivation in the presence of increasing amounts of homologous immune serum

This investigation was undertaken to select antigenic variants of a Borrelia burgdorferi strain in vitro. The original strain BITS was cultivated in BSK medium supplemented with increasing concentrations of homologous hyperimmune serum raised in rabbits. After a few serial passages starting from a subinhibitory serum dilution of 1:800 in BSK up to 1:200, a variant named BITSv was obtained; it grew abundantly like the control culture in the presence of hyperimmune serum. Analysis of the antigenic pattern of the original and derived variants by Western blotting revealed that BITSv, compared to the original strain BITS, had lost the reactivity with the immune serum at the level of the oligosaccharide moiety. These experiments, designed to mimic the possible action of antibodies that arise during a Borrelia infection, suggest that lipopolysaccharides are surface located and that they play a role in the integrity of the outer membrane during the multiplication of Borrelia burgdorferi.     

Changes in the glycosylation of IgG in the collagen-induced model of arthritis

It is now well established that rheumatoid arthritis patients have reduced levels of galactose on their immunoglobulin G (IgG) molecules compared with normal individuals. We have investigated whether, in an experimentally induced model of arthritis, similar glycosylation changes on IgG are to be found. Serum IgG was isolated from collagen-induced arthritic DBA/1 mice and a control group, and the glycosylation of the IgG in these preparations was compared using lectin blotting. The glycosylation of IgG in immune complexes was also analysed. Arthritic mice exhibited similar glycosylation changes on their IgG as observed for rheumatoid arthritis patients. On average, there was less galactose on the IgG from arthritic mice than from the control group, but this difference was of borderline significance. However, theN-acetylglucosamine content of IgG was significatly elevated in arthritic mice. There was no difference in the sialic acid content of IgG in the two groups. The results for immune complexes were similar to those obtained for serum IgG, but the data were limited by insufficient numbers. The similarity in glycosylation changes in collagen-induced arthritis and in patients with rheumatoid arthritis suggests that common pathogenic mechanisms may be involved.     

Reduced amyloid-A-degrading activity in serum in amyloidosis associated with rheumatoid arthritis.

The ability to degrade amyloid A fibrils was studied in the serum of 31 patients with amyloidosis associated with rheumatoid arthritis, 33 patients with rheumatoid arthritis without amyloidosis, and 47 healthy controls. Fibrillar amyloid A protein and the radial diffusion method were used. The mean degrading activity in serum was significantly lower in patients with rheumatoid arthritis complicated by amyloidosis (58 +/- 19% SD of the activity in a pooled sample of sera from 100 healthy blood donors used as standard) than in patients with rheumatoid arthritis alone (78 +/- 14%; p less than 0.001) or controls (99 +/- 19%; p less than 0.001). Alpha 1-antitrypsin, concentrations of which were raised in both groups of patients, inhibited the degrading activity in serum even in low concentrations. A negative correlation between degrading activity and alpha 1-antitrypsin concentrations was observed. These findings suggest that reduced amyloid-A-degrading activity is due to inhibition rather than to deficiency of enzyme.     

Antiperinuclear activity in lung carcinoma patients

Summary Antiperinuclear factor (APF) might be a specific serum rheumatoid factor directed towards keratohyaline granules. It was found to be present in 40 of 79 (50.6%) patients with primary and in 21 of 36 (58.3%) patients with metastatic lung cancer, compared with 12 of 95 (12.6%) sex- and age-matched normal controls. Additionally, APF frequency and titer correlated well with tumor dissemination, even though no relationship could be shown with histopathological type.