Rheumatoid Factor In Patients Research Articles

Functional affinity of IgM rheumatoid factor in patients with rheumatoid arthritis and other autoimmune diseases.

The functional affinity of IgM rheumatoid factors (RF) was measured in 31 patients with rheumatoid arthritis (RA), 24 with systemic lupus erythematosus (SLE), 13 with Sjögren's syndrome (SS), and in 13 seropositive healthy individuals. The functional affinity of IgM RF from patients with RA was significantly lower than in the other clinical groups studied. In addition, there was a significant inverse correlation between functional affinity and titre of IgM RF in all the groups. These results suggest that the usual mechanisms of affinity based selective pressure (somatic diversification and antigen selection) may operate differently for autoantibodies to serum antigens such as IgG.

IgG as antigen in human rheumatoid disease.

Although the events underlying the expression of rheumatoid factor in patients with rheumatoid arthritis remain unknown, evidence from both human and animal studies has suggested a role for altered or complexed IgG. Similarly, altered or complexed IgG may also participate in initiating and sustaining inflammation in this disease. Potentially relevant differences in the glycosylation and conformation of rheumatoid IgG compared to IgG from healthy individuals have been detected by several investigators. The latter observations have raised new possibilities concerning mechanisms underlying the pathogenesis of rheumatoid arthritis and, in particular, the production of rheumatoid factor.

Leu-1(CD5) B Cell Subpopulation in Patients with Various Liver Diseases – Special Reference to Hepatitis B Virus Carrier and to Changes Caused by Prednisolone Therapy

A human B cell subpopulation identifiable by the expression of the cell surface antigen Leu-1(CD5) was examined in peripheral blood lymphocytes obtained from patients with various liver diseases by dual two-color fluorescence flow cytometry. A significantly high level of Leu-1 B cells in chronic hepatitis and in liver cirrhosis especially in hepatitis B surface antigen (HBsAg)-positive patients (hepatitis B virus carriers) was observed. However, there was no significant difference between the percentage in controls and those in patients with acute hepatitis and primary biliary cirrhosis. Moreover, we could not demonstrate a correlation between the incidence of these cells and positive IgM class rheumatoid factor in patients with liver diseases. The percentage of Leu-1 B cells in patients who had been receiving prednisolone at the time of this study was lower than that in healthy controls. These results suggested that Leu-1 B cells might be associated with the continuation of the HBsAg-positive state and that the presence of the Leu-1 B cell population might be modified by prednisolone administration.

Circulating IgM rheumatoid factors in patients with primary Sjögren's syndrome.

The importance of circulating rheumatoid factors (RF) in primary Sjögren's syndrome (primary SS) was evaluated retrospectively by examining medical case records of 80 consecutive patients. Increased levels of IgM RF, determined by the Waaler test, the latex fixation test and/or the ELISA test, were found in 47 patients (59%). Follow-up examination of the 41 patients in whom more than one (mean 4.9 (2-12)) RF determination over at least a two-year period (mean 5.6 (2-13) was present, showed that 12/41 patients (29%) were permanently RF-negative, 7/41 (17%) exhibited both positive and negative RF values and 22/41 (54%) were permanently RF positive. Variations in IgM RF levels were unrelated to disease duration. Except for involvement of joints, extraglandular manifestations were more common in patients with increased levels of RF. This finding, however, was only significant within the group of more rarely occurring extraglandular manifestations (serositis, interstitial nephritis, cutaneous vasculitis, lymphoproliferative disorders and intermittent fever) (p less than 0.01). IgM RF levels were likewise positively correlated (p less than 0.001) to positivity of IgG antinuclear antibodies as well as to the plasma concentrations of immunoglobulins.

Circulating immune complexes and immunoglobulin A rheumatoid factor in patients with mesangial immunoglobulin A nephropathies.

Circulating immune complexes (CIC) containing IgA and C3 were elevated in 48% of IgA nephropathy patients; IgA1 was the predominant subclass. IgA1-IgG CIC were detected in 44%, IgA2-IgG CIC in 7%, and IgM-IgA1 CIC in 16% of the patients. No IgM-IgA2 CIC were detectable. Sucrose gradient ultracentrifugation indicated that IgG-IgA1 CIC were predominantly of intermediate (13-19S) size whereas IgA1-C3 CIC sedimented from 11S to 19S. At acid pH, isolated CIC revealed the presence of substantial amounts of 7S IgA. One third of the patients had elevated serum IgA rheumatoid factor (RF) of both polymeric and monomeric forms despite normal levels of IgM-RF; 87% of patients with elevated IgA-RF had IgA1-IgG CIC. These results indicate that the IgA1 component of CIC in patients with IgA nephropathy is not necessarily of mucosal origin and suggest that a portion of these CIC consists of IgA RF immunologically complexed with autologous IgG.

Expression of a cross-reactive idiotype on rheumatoid factor in patients with Sjogren's syndrome.

Primary Sjogren's syndrome (SS) is a systemic autoimmune disorder characterized by lymphocytic infiltration of salivary and lacrimal glands. These patients have evidence of marked B cell hyperactivity, including the production of autoantibodies such as rheumatoid factor (RF) and an increased frequency of non-Hodgkin's lymphoma. We now demonstrate that RF from 12/15 SS patients contains a cross-reactive idiotype (CRI) on their kappa light chain defined by a monoclonal antibody (MoAb 17-109) and immunoblotting. This CRI was associated with immunoglobulin (Ig) A-RF, and to a lesser extent with IgM-RF molecules on the basis of direct binding studies. With the use of immunoperoxidase techniques to stain frozen tissue sections, B cells containing cytoplasmic Ig reactive with MoAb 17-109 were detected in the salivary gland biopsies from 11/12 SS patients at high frequencies, and in the blood from the same patients at much lower frequencies. One patient with pre-existant SS developed non-Hodgkin's lymphoma with tumor cells and RF paraprotein reactive with MoAb 17-109. Evaluation of serial biopsies over a 4-yr period showed a progressive increase in the proportion of B cells bearing the CRI. In contrast, synovial membrane biopsies from RA patients lacking sicca symptoms did not contain B cells expressing the CRI. Because previous studies have demonstrated that MoAb 17-109 detects a CRI on RF paraproteins from patients with lymphoma, B cells bearing this CRI may have increased frequency of neoplastic transformation. SS patients provide an opportunity to study the expression of this CRI and to understand the transition of B cell clones from autoimmune proliferation to neoplastic transformation.

IgG, IgA and IgM Rheumatoid Factors in Patients with Glomerulonephritis

Rheumatoid factors (RF), autoantibodies to IgG, have been postulated to have some pathogenetic role in the development of some types of glomerulonephritis. A simple and sensitive solid-phase fluorescence immunoassay was employed to determine whether IgG, IgA and IgM RF were detectable in sera from patients with various types of glomerulonephritis, rheumatoid arthritis (RA) and those with various streptococcal infections. IgG, IgA and IgM RF were significantly increased in the majority of patients with RA, lupus nephritis (SLE), acute poststreptococcal glomerulonephritis (APSGN) and various streptococcal infections. The titers of IgG and IgA RF were significantly higher in patients with APSGN than in those with simple pharyngitis. IgM RF was increated in patients with IgA nephropathy (IgA-N) and in those with membranoproliferative glomerulonephritis type I (MPGN). No significantly high RF was observed in membranous nephropathy (MN) or chronic mesangial proliferative glomerulonephritis without IgA deposition (PGN). It is suggested that some autologous immune mechanisms may be involved in the pathogenesis of some types of glomerulonephritis.

Frequency and Clinical and Transfusional Significance of Rheumatoid Factor in Patients with Haemophilia and von Willebrand's Disease

Using a solid-phase radioimmunoassay for IgM rheumatoid factor, increased levels were found in 24% or 82 patients with haemophilia A, in 4 of 11 patients with haemophilia B, in 2 of 11 patients with haemophilia A with inhibitors and in 4 of 12 with von Willebrand’s disease. The levels of rheumatoid factor increased significantly (p < 0.02) after factor VIII concentrate or cryoprecipitate transfusions. No clinical or transfusional side effects could be attributed in these patients in relation to the presence of rheumatoid factor.

Circulating immune complexes and rheumatoid factors in patients with farmer's lung.

Circulating IgG immune complexes (CICs), IgM rheumatoid factors (RFs), complement level (C3 and C4), and IgG antibodies to Aspergillus fumigatus, Aspergillus umbrosus, Thermoactinomyces vulgaris, and Micropolyspora faeni were analysed in the sera of 14 patients with farmer's lung (FL), 10 in the acute and four in the subacute phase of the disease. Ten spouses of FL patients served as exposed healthy controls. C3 and C4 were measured fluoronephelometrically. C3 levels were above the normal range and C4 levels near the upper limit of the normal range in both patients and controls; no statistically significant difference between patients and controls were observed. CICs were determined by enzyme immunoassays (EIA) of conglutinin-binding (KgB) and Clq-binding (ClqB). CIC levels above the normal range were detected in 12 (KgB-EIA) and nine (ClqB-EIA) of the patients and three (KgB-EIA) and six (ClqB-EIA) of the controls. No statistically significant differences were found in the mean levels between patients and controls. In contrast, RF levels in the acute phase of FL were significantly higher in the patients (P less than 0.01) than in the controls. CICs correlated positively with most microbial IgG antibodies, but negatively with RFs. RFs also correlated negatively with microbial IgG antibodies, as well as with both C3 and C4. In FL, the increased RF level may, in the absence of increased CIC and decreased complement levels, represent an immune response (IgM anti-IgG autoantibodies) induced by local mechanisms of IgG immune complexes in the lungs.

Effect of pregnancy on immune complexes and rheumatoid factors in patients with rheumatoid arthritis: Pope RM, Yoshinoya S, Rutstein J, Persellin RH: Am J Med 1983; 74: 973–979

Effect of pregnancy on immune complexes and rheumatoid factors in patients with rheumatoid arthritis: Pope RM, Yoshinoya S, Rutstein J, Persellin RH: Am J Med 1983; 74: 973–979

Effect of pregnancy on immune complexes and rheumatoid factors in patients with rheumatoid arthritis

Rheumatoid arthritis is associated with circulating and intra-articular immune complexes and rheumatoid factors. The clinical activity of rheumatoid arthritis improves during pregnancy in the majority of women, with exacerbation following delivery. Concentrations of immune complexes, as detected by the Clq-binding assay, the Clq-solid phase assay, and the monoclonal rheumatoid factor-solid phase assay, decreased during gestation, with elevations following delivery. Concentrations of IgM-rheumatoid factor and IgG-rheumatoid factor, analyzed by radioimmunoassay, changed variably during pregnancy, increasing in some patients and decreasing in others. When examined serially before, during, and following pregnancy, changes in the concentration of circulating immune complexes and/or rheumatoid factors corresponded with the clinical changes in three patients. These observations document the significant effect of gestation on the concentration of circulating immune complexes in patients with rheumatoid arthritis. They also support the role of these laboratory tests in monitoring the clinical course of rheumatoid arthritis.

Inheritance of immunoglobulin M rheumatoid-factor idiotypes.

The idiotypic determinants on IgM rheumatoid factor (RF) from a single family have been analyzed. Rabbit Fab'2 antiidiotypic antibody was prepared against purified IgM-RF from a patient with rheumatoid arthritis. As measured by radioimmunoassay, the antiidiotype reacted with at least 90% of the patient's RF, but not with non-RF immunoglobulins from the same serum, nor with 10 of 11 polyclonal and monoclonal RF from unrelated individuals. Cross-reacting idiotypes were detected on RF in four of the patients' first degree relatives, spanning three generations, without apparent relation of HLA type or clinical rheumatoid arthritis. These results suggest that IgM-RF associated idiotypes were inherited in this family.

Musculoskeletal manifestations of bacterial endocarditis.

The records of 180 patients out of 247 with bacterial endocarditis were examined. 50 patients had rheumatic manifestations. In 10 there was arthritis of 2-12 weeks' duration before diagnosis; 19 had myalgia/arthralgia; 17 had back or neck pain; 14 had demonstrable arthritis; and 2 tenosynovitis of the foot. Of the 14 patients with arthritis, 8 had monarticular arthritis and 6 polyarticular. All but one patient had a raised erythrocyte sedimentation rate, and in one patient rheumatoid factor was positive. The rheumatic features responded when the endocarditis was treated. Some of the symptoms undoubtedly resulted from the infection and fever of the endocarditis, and emboli may have caused the transient aches but there was no evidence that they caused the synovitis in the patients with arthritis. The rheumatic manifestations of bacterial endocarditis can mimic other rheumatic diseases and disguise the underlying disease.

Rheumatoid factor in diabetes mellitus (author's transl)

This study was undertaken to try to determine the incidence of rheumatoid factor in patients with diabetes mellitus by the Hyland RA slide test and the RAHA test (the sensitized sheep red cell agglutination test). Sera from 507 patients with diabetes mellitus and 2073 controls were investigated for the presence of rheumatiod factors. RA test was positive in 8.7 per cent and RAHA test in 6.1 per cent in sera from patients with diabetes mellitus compared to 4.1 percent and 3.6 per cent respectively in healthy subjects.

In vivo and in vitro responses to autologous IgG in patients with rheumatoid arthritis.

AbstractThe presence of rheumatoid factor in patients with rheumatoid arthritis remains unexplained and may be etiologically important. An attempt has been made to determine whether patients with seropositive rheumatoid arthritis show basic immunologic responses to IgG. Various immunologic parameters of antigen recognition were measured in 9 patients and 3 controls. No immediate or delayed cutaneous hypersensitivity was noted to native or aggregated autologous IgG, nor could in vitro lymphocyte blast cell transformation be induced with these proteins. Rebuck skin windows showed no unusual responsiveness to native IgG. The negative results indicate that either IgG is not the immunogen responsible for rheumatoid factor or that patients with rheumatoid arthritis retain a state of partial tolerance. Evidence supporting the concept that rheumatoid factor may interfere with the phlogistic potential of aggregated γ‐globulin was also found.

A serologic method using charcoal particles from commercial India ink. Application to several antigen-antibody systems with special reference to the rheumatoid factor.

A technique utilizing antigen-coated charcoal particles for antibody detections is presented. The stability of the suspension of charcoal particles, provided by a commercial india ink preparation, allows an easy and simplified method of antibody detection. Its application to antigen-antibody systems requiring lower values of pH can be envisaged. When used in the detection of the Rheumatoid Factor in patients with typical Rheumatoid Arthritis and in a general hospital population the test showed a promising degree of sensitivity.

Dilution Dependent Autoinhibition of Agglutination in Rheumatoid Arthritis Sera and Rabbit Anti-Human γG Antisera

Summary Sera from patients with rheumatoid arthritis were titrated with human γG-immunoglobulin coated tanned sheep cells at six cell concentrations ranging from 0.125% to 2.0%. Double logarithmic plots of titer vs. cell concentration were linear. Fifteen of 21 cases (71%) yielded slopes greater than -1.0 reflecting an abnormally large decrease in titer with increasing cell concentration. Previous work (3) has shown that the abnormal titer decreases were due to an autoinhibitory component in the patient's own γG. In the present study it was found that increased slopes were independent of RF titer, duration of disease, or age of patient. Increased slopes were associated with a greater frequency of diagnosis of rheumatoid arthritis as compared to nonrheumatoid disease. Comparison of sera and synovial fluids derived from the same individual revealed identical slope values even when RF titers of both fluids differed appreciably. Certain sera when studied with human and rabbit γG coated cells revealed elevated slopes in both test systems; others, only in the human system. Block titration of rabbit antisera against purified human γG yielded normal -1.0 slopes in the initial bleedings. However, antisera obtained 3 to 4 weeks after initial immunization showed elevated slopes. This was true when agglutination titers were increasing, as well as when such titers were decreasing. It is suggested that in RF sera at least, elevated slopes are due to a dilution dependent autoinhibition of agglutination which arises from the interaction between at least part of the patient's rheumatoid factor with his autologous γG.

1965. Connectivetissue disease and rheumatoid factors in patients with renal transplants

1965. Connectivetissue disease and rheumatoid factors in patients with renal transplants

CONNECTIVE-TISSUE DISEASE AND RHEUMATOID FACTORS IN PATIENTS WITH RENAL TRANSPLANTS.

AN impressive body of experimental evidence can be summarized by the statement that graft rejection is initiated by an immunologic process.1 Similarly, there is evidence that immunologic events may determine certain features of rheumatic disease in man.2 Furthermore, there are at least superficial resemblances between the graft-versus-host response and the generalized connective-tissue diseases.3 For these reasons, attention is naturally paid to the possible occurrence of connective-tissue alterations in patients harboring grafted tissues. Our interest in this problem was stimulated by the observation that certain patients with renal transplants had evidence of rheumatic disease and a change from negative to positive . . .

Rheumatoid factors in patients with silicosis with round nodular fibrosis of the lung in the absence of rheumatoid arthritis with a note on the failure to induce such factors in animals.

AbstractSera of 10 patients with silicosis and round nodular fibrosis of the lung in the absence of rheumatoid arthritis had positive rheumatoid factor tests. The proteins responsible for this were identical or at least closely related to those seen in patients with rheumatoid arthritis. It was not possible to induce “rheumatoid factor‐like” proteins in rats and guinea pigs by prolonged injections of silica. The possible significance of these proteins in the pathogenesis of the disease is discussed.