IgM Rheumatoid Factor Concentration Research Articles

Autoantibodies to Malondialdehyde-Acetaldehyde Are Detected Prior to Rheumatoid Arthritis Diagnosis and After Other Disease Specific Autoantibodies.

To examine serum autoantibodies to malondialdehyde-acetaldehyde (MAA) prior to rheumatoid arthritis (RA) diagnosis. Concentrations of anti-MAA antibody isotypes, anti-cyclic citrullinated peptide 2 (anti-CCP-2), and IgM rheumatoid factor (IgM-RF) were evaluated before and after RA diagnosis in samples from cases (n = 214) and controls (n = 210). The timing of elevations in autoantibody concentrations relative to RA diagnosis was explored using separate mixed models for each antibody and/or isotype. Associations between prediagnosis autoantibody concentrations in RA patients were examined using mixed effects linear regression models. Concentrations of IgG (log2 difference 0.34) and IgA (log2 difference 0.43) anti-MAA antibodies in RA patients diverged from controls at 3.0 years and 2.3 years prior to diagnosis, respectively (P < 0.05 for both). There was no evidence of case-control divergence for IgM anti-MAA antibody concentration. Anti-CCP-2 and IgM-RF concentrations diverged between RA patients and controls beginning at 17.6 years and 7.2 years prior to RA diagnosis, respectively. All 3 anti-MAA antibody isotypes (IgA, IgM, and IgG) were significantly associated with anti-CCP-2 antibody and RF concentrations prior to diagnosis (β = 0.22-0.27 for IgM-RF; β = 0.44-0.93 for anti-CCP-2) (P < 0.001). IgG and IgA anti-MAA autoantibodies are elevated prior to RA diagnosis but appear later in the preclinical course than anti-CCP-2 or RF. These findings suggest that MAA formation and anti-MAA immune responses could play a role in the transition from subclinical autoimmunity to clinically apparent arthritis.

Production of IgM rheumatoid factor by normal lymphocytes after stimulation with preparations containing IgM rheumatoid factor from patients with juvenile arthritis.

Preparations containing IgM rheumatoid factor (RF) and hidden IgM RF were isolated from the serum samples of nine patients with juvenile rheumatoid arthritis. Six of these preparations stimulated lymphocytes from normal donors to produce IgG and IgM, of which up to 11% had IgM RF activity. In contrast, the polyclonal activator pokeweed mitogen also stimulated IgM production, but only 1% had IgM RF activity. A relation between the activator and IgM RF or hidden IgM RF is suggested. This is based on the positive correlation between IgM RF concentration in these preparations and their ability to stimulate lymphocytes to produce IgG, IgM, and IgM RF. These data indicate that preparations from patients with juvenile rheumatoid arthritis containing IgM RF and hidden IgM RF are potent stimulants of lymphocytes from normal donors, with specific production of IgM RF.

Complement-mediated inhibition of immune precipitation in rheumatoid vasculitis

Complement-mediated inhibition of immune precipitation (CMIP) was measured in patients with rheumatoid arthritis (RA), rheumatoid vasculitis (RA VASC), patients with skin vasculitis not associated with a systemic connective tissue disease and normal healthy controls. CMIP was impaired in 100% (14/14) of the RA vasculitic patients, 60% (12/20) of the RA patients and 22% (2/9) of the dermovasculitic patients. The degree of impairment of CMIP was significantly greater in the RA vasculitic patients compared to the non-vasculitic patients. This difference was due to the significantly lower complement levels and the presence of higher concentrations of an inhibitor of CMIP in the RA vasculitic sera. The levels of this inhibitory activity correlated significantly with IgM rheumatoid factor concentration. Serial studies in three patients with RA vasculitis treated with corticosteroids and immunosuppressive drugs showed significant clinical improvement in two patients, which was associated with improvement in CMIP, reduction in circulating immune complex levels and reduction in IgM rheumatoid factor concentrations.

Complement mediated inhibition of immune precipitation in rheumatoid arthritis: studies on interaction of heat aggregated IgG with IgM rheumatoid factor.

Serum samples from patients with seropositive rheumatoid arthritis contain an inhibitor of complement mediated inhibition of immune precipitation (CMIP). This inhibitory effect can be produced by the addition of either purified monoclonal or polyclonal IgM rheumatoid factor (RF) to human serum. The specificity of the rheumatoid factor influences the degree of inhibition, and when precipitation occurs the rheumatoid factor coprecipitates with the antigen-antibody complex. In rheumatoid sera there was a significant positive correlation between IgM RF concentration and inhibitory activity, though the range of inhibitory activity seen for the same concentration of rheumatoid factor was considerable. Small quantities of heat aggregated IgG (HAGG) had a much greater effect on the measurement in an enzyme linked immunosorbent assay (ELISA) of IgM RF than they did on the inhibitory activity of IgM RF in the CMIP assay. Larger quantities of HAGG initiated complement activation and increased the precipitation of immune complexes. IgM RF reduced the complement activating properties of HAGG by reducing the amount of Clq which bound to the aggregate. The mechanisms by which IgM RF overcomes CMIP in rheumatoid sera may involve its inhibitory effects on the binding of Cl to the antigen-antibody complex.

A quantitative assay for IgA rheumatoid factor

We have developed a solid-phase radioimmunoassay capable of detecting nanogram quantities of human IgA rheumatoid factor (RF) in biological fluids. Human IgM RF, IgG RF, IgG, IgA, IgM and whole serum did not significantly interfere with the IgA RF assay. Patients with sero-positive rheumatoid arthritis (RA) had significantly higher concentrations of IgA RF than sero-negative RA patients or healthy adult controls. Concentrations of IgA RF in paired sera and synovial fluids from sero-positive RA patients were comparable. Levels of IgA RF demonstrated a moderately good correlation with levels of IgM RF in sero-positive RA sera ( r = 0.673). However, the ratio of IgA RF concentration to IgM RF concentration in sero-positive RA sera varied widely.

The interference of IgM rheumatoid factor in enzyme-linked immunosorbent assays of rubella IgM and IgG antibodies

The interference of IgM rheumatoid factor (RF) in the indirect enzyme-linked immunosorbent assay (ELISA) for rubella IgM and IgG antibodies was evaluated quantitatively. In an ELISA for rubella IgM antibodies IgM RF produced false positive results in tests of sera with a rubella IgG concentration exceeding approximately 30 I.U./ml and an IgM RF concentration higher than 3.5 I.U./ml as determined by ELISA. Sera from 3 of 70 patients with recent rubella and sera from a similar proportion of blood donors contained IgM RF in a concentration exceeding this level. The false positive results were reproduced when an IgM RF preparation was added to sera containing rubella IgG. The rubella IgG values in ELISA, however, decreased after the addition of IgM RF . RF was absorbed by incubation of sera with a suspension of latex particles coated with aggregated human IgG. This method prevented the false positive results of the rubella IgM assay and increased the rubella IgM values of rubella convalescent sera. The activity in the rubella IgG assay also increased after absorption of RF. The interference of RF has been explained by a secondary binding of RF to rubella IgG-antigen complexes. The RF might subsequently be detected by the anti-IgM conjugate or compete with the anti-IgG conjugate. The common occurrence of IgM RF in concentrations sufficient to produce false positive results of the ELISA for specific IgM antibodies necessitates routine testing of IgM antibody positive sera for RF by a sensitive method and/or absorption of RF from such sera.

Estimation of IgM rheumatoid factors by fluorimetry.

Sheep red cells coated with rabbit IgG antibody may be used to detect IgM rheumatoid factors either by agglutination or microscopically by the fluorescence of antihuman IgM antibody conjugate bound to rheumatoid factors on the cell surface. By substituting for red cells the plastic surface of a filter disc coated with rabbit IgG it was possible to elute the bound conjugate and measure the fluorescence in a fluorimeter. The results of both the sheep cell agglutination test and the fluorescence test agreed quite well for the majority of sera; both tests seemed to reflect IgM rheumatoid factor concentrations in these sera. The difficulties encountered in attempting to define and measure accurately rheumatoid factor concentrations in a serum are emphasised.