IgG Rheumatoid Factor Levels Research Articles

False-positive detection of IgM anti-severe acute respiratory syndrome coronavirus 2 antibodies in patients with rheumatoid arthritis: Possible effects of IgM or IgG rheumatoid factors on immunochromatographic assay results.

Objectives:The severe acute respiratory syndrome coronavirus 2 causes coronavirus disease 2019. A serological test is conducted to determine prior infection by severe acute respiratory syndrome coronavirus 2. We investigated whether the results of anti-severe acute respiratory syndrome coronavirus 2 antibody tests are modified in patients with rheumatoid arthritis.Methods:Patients in Japan with rheumatoid arthritis were recruited at Sagamihara Hospital from July 2014 to October 2015 (n = 38; 2014 cohort) and at Tokyo Hospital from June to October 2020 (n = 93; 2020 cohort). Anti-severe acute respiratory syndrome coronavirus 2 antibodies were measured by electrochemiluminescence immunoassay or immunochromatographic assay.Results:Anti-severe acute respiratory syndrome coronavirus 2 antibodies were not detected in any of the samples from rheumatoid arthritis patients tested by electrochemiluminescence immunoassay. Anti-severe acute respiratory syndrome coronavirus 2 antibodies were detected by immunochromatographic assay in the 3 (7.9%) serum samples in the 2014 cohort and 15 (16.1%) serum samples in the 2020 cohort. The IgM rheumatoid factor levels were increased in rheumatoid arthritis patients with IgM anti-severe acute respiratory syndrome coronavirus 2 antibodies detected by immunochromatographic assay (mean ± standard deviation (IU/ml), 1223.0 ± 1308.7 versus 503.6 ± 1947.2; P = 0.0101). The levels of IgG rheumatoid factor were also upregulated in rheumatoid arthritis patients with IgM anti-severe acute respiratory syndrome coronavirus 2 antibodies detected by immunochromatographic assay (4.0 ± 0.7 versus 2.4 ± 0.9; P = 0.0013).Conclusion:The results of IgM anti-severe acute respiratory syndrome coronavirus 2 antibody testing by immunochromatographic assay are modified by IgM or IgG rheumatoid factors in rheumatoid arthritis patients.

Does the Course of Disease Influence the Development of Fatigue in Rheumatoid Arthritis Patients?

Abstract Patients with rheumatoid arthritis (RA) typically have many permanently inflamed joints. The inflammation inside the body can lead to general physical weakness, exhaustion, and drowsiness. This feeling of extreme tiredness is also called “fatigue”. Some people find this to be the worst symptom of the disease. However, the clinical significance of fatigue and its pathogenesis have not been recognised. This study aimed to determine the development of fatigue depending on activity and aggressiveness of RA. To achieve the goal, patients were interviewed and indicators of disease activity and aggressiveness were determined: rheumatoid factor (RF), anti-cyclic citrullinated peptide antibodies (anti-CCP), erythrocyte sedimentation rate (ESR), C reactive protein (CRP), immunoglobulins IgA RF, IgM RF, IgG RF and anti-carbamylated protein antibodies (anti-CarP). Based on the results of the survey, RA patients were divided into two groups — with and without fatigue. In the group of RA patients with fatigue, statistically more often an increase in IgA RF, IgM RF, and IgG RF levels was observed in those with elevated RF level, higher IgM RF and IgG RF levels were associated with increase in IgA RF level, and increase in the IgG RF and anti-CarP levels with elevation in the IgM RF level. A higher IgG RF level contributed to a higher anti-CarP level increase. Significant differences in the levels of clinical and laboratory inflammatory markers were not observed between the RA patients with and without fatigue. The obtained data suggest that the aggressive course of RA, more than inflammation, may contribute to the development of fatigue in RA patients.

Rheumatoid factor isotypes in localized scleroderma.

Localized scleroderma is a connective tissue disorder that is sometimes accompanied by various immunological abnormalities. In this study, we analysed serum levels of rheumatoid factor (RF) isotypes in patients with localized scleroderma and in normal controls to determine if any of these isotypes reflect the severity of the disease. IgM RF, IgG RF and IgA RF were positive in 30%, 21%, and 7% of the patients, respectively. The levels of IgM RF were significantly higher in the patients with generalized morphea (GM), the most severe form of localized scleroderma, than those with linear scleroderma (LS) (P < 0.005) or normal controls (P < 0.0005). The levels of IgG RF were significantly higher in patients with GM than normal controls (P < 0.05). The levels of IgA RF were significantly higher in patients with GM or LS than normal controls (P < 0.001 and P < 0.01, respectively). The count of sclerotic lesions was significantly higher in patients with IgM RF than those without (P < 0.05). These results suggest that the presence of RF isotypes is one of the immunological abnormalities of localized scleroderma. IgM RF seemed to be most useful of these three factors to determine the severity of disease.

Recombinant cytomegalovirus glycoprotein gB (UL55) induces an autoantibody response to the U1-70 kDa small nuclear ribonucleoprotein.

Human cytomegalovirus (CMV) infection can be life threatening in the immune compromised and is associated with congenital defects and / or mental retardation in the neonate. The demonstrated association between CMV infection and rheumatoid factor (RF) raised the possibility of an induction of an autoimmune response upon vaccination with a candidate CMV vaccine, glycoprotein gB (UL55). The antibody responses generated after injections of an adenovirus-gB construct (Ad-gB) were studied in autoimmune-prone (MRL/mpj) and normal (BALB.k, C3H, and BALB/c) mice. Enzyme-linked immunosorbent assay and immunoblot analyses were done to identify the autoantibodies produced following immunization. Immunization with Ad-gB induced a significant IgG anti-viral response in all strains tested (p < 0.0001) compared to phosphate-buffered saline or HeLa controls. Ad-gB induced a significant IgG autoantibody response (p > 0.005) to the U1-70 kDa spliceosome protein in both autoimmune and normal strains whereas immunization with recombinant human La/SS-B did not. Autoantibodies to U1-70 kDa are part of the anti-ribonucleoprotein response seen in systemic lupus erythematosus and mixed connective tissue disease. Low levels of IgG RF and anti-double-stranded DNA antibodies were also induced. This study raises concern that immunization with CMV gB in individuals genetically predisposed to autoimmunity could trigger the development or acceleration of an autoimmune disease.

Clinical and serologic manifestations of autoimmune disease in MRL-lpr/lpr mice lacking nitric oxide synthase type 2.

Nitric oxide (NO) is an important mediator of the inflammatory response. MRL-lpr/lpr mice overexpress inducible nitric oxide synthase (NOS2) and overproduce NO in parallel with the development of an autoimmune syndrome with a variety of inflammatory manifestations. In previous studies, we showed that inhibiting NO production with the nonselective nitric oxide synthase (NOS) inhibitor NG-monomethyl-arginine reduced glomerulonephritis, arthritis, and vasculitis in MRL-lpr/lpr mice. To define further the role of NO and NOS2 in disease in MRL-lpr/lpr mice, mice with targeted disruption of NOS2 were produced by homologous recombination and bred to MRL-lpr/lpr mice to the N4 generation. MRL-lpr/lpr littermates homozygous for disrupted NOS2 (-/-), heterozygous for disrupted NOS2 (+/-), or wildtype (+/+) were derived for this study. Measures of NO production were markedly decreased in the MRL-lpr/lpr (-/-) mice compared with MRL-lpr/lpr (+/+) mice, with intermediate production by the MRL-lpr/lpr (+/-) mice. There was no detectable NOS2 protein by immunoblot analysis of the spleen, liver, kidney, and peritoneal macrophages of the (-/-) animals, whereas that of (+/+) was high and (+/-) intermediate. The (-/-) mice developed glomerular and synovial pathology similar to that of the (+/-) and (+/+) mice. However, (-/-) mice and (+/-) mice had significantly less vasculitis of medium-sized renal vessels than (+/+) mice. IgG rheumatoid factor levels were significantly lower in the (-/-) mice as compared with (+/+) mice, but levels of anti-DNA antibodies were comparable in all groups. Our findings show that NO derived from NOS2 has a variable impact on disease manifestations in MRL-lpr/lpr mice, suggesting heterogeneity in disease mechanisms.

Prospective study of early rheumatoid arthritis. II. Association of rheumatoid factor isotypes with fluctuations in disease activity.

Thirty-three patients with early peripheral synovitis were followed up for two to four years in order to study the relationship between fluctuations in rheumatoid factor (RF) levels and indices of clinical activity. Twenty-eight of these patients developed classical/definite rheumatoid arthritis (RA). Seventeen patients developed erosive disease of their hands and wrists and thirteen had a positive RF agglutination test. Nineteen patients had raised levels of IgM, RF, IgA, RF, or IgG RF as measured by isotype-specific ELISA techniques. The within-patient fluctuations in IgA RF levels correlated significantly with the corresponding fluctuations in grip strength (p less than 0.05), erythrocyte sedimentation rate (ESR) (p less than 0.01), and a composite index of disease activity (p less than 0.02). IgG RF levels were also associated with changes in ESR and grip strength, but IgM RF showed only a weak association with fluctuations in ESR and not with any other clinical parameters. It is suggested that serum IgA RF may be a useful marker of disease activity in rheumatoid arthritis.

IgG and IgM rheumatoid factors in rheumatoid arthritis. Quantitative response to penicillamine therapy and relationship to disease activity.

Penicillamine treatment of patients with rheumatoid arthritis (RA) leads to falling titers of agglutinating IgM rheumatoid factor (RF), but its effect on IgG RF has not been described. Using specific solid phase radioimmunoassays, we have determined serial levels of IgM RF and IgG RF in 18 patients receiving penicillamine for 1 year, and correlated the results with the change in RA activity. Mean IgM RF levels fell to 76 +/- 10% (mean +/- SEM) after 3 months, and 30 +/- 5% of the pretreatment value after 1 year of penicillamine treatment. This decline was greater than that for total IgM (P less than 0.0001), indicating a selective reduction of RF. Patients receiving maintenance doses of 750 mg/day manifested more rapid and greater decreases than did those given 250 mg/day. In contrast, serial mean IgG RF levels did not change significantly, and actually increased in 6 of 18 cases. At onset, there was a significant correlation with erythrocyte sedimentation rate for both IgM RF (r = 0.535, P = 0.05) and IgG RF levels (r = 0.570, P = 0.02). But changes in RF concentration demonstrated no correlation with changes in either erythrocyte sedimentation rate or joint score over the 1-year period, suggesting that circulating IgM RF or IgG RF levels may be unrelated to the degree of RA activity.

IgG rheumatoid factor. Detection by enzyme immunoassay in rheumatoid arthritis and normal subjects

IgG rheumatoid factors were demonstrated by enzyme immunoassay using, as antigen, goat antibodies to human serum albumin in the form of immune complexes. Elevated levels of IgG rheumatoid factor were noted in the majority of patients with seropositive rheumatoid arthritis but also relatively often in normal blood donors. Reactivity of IgG rheumatoid factor was in most instances inhibitable by IgG from various species, including man. Exceptionally, restricted specificity towards IgG from bovidae, was recognized.

Problems in the assessment of disease activity in ankylosing spondylitis.

Serial assessments of disease activity using clinical, laboratory and thermographic indices were made on 20 patients with ankylosing spondylitis (AS) before and after active in-patient exercise classes and two months after discharge. Clinical measurements and the erythrocyte sedimentation rate suggested decreased activity by the time of the final assessment but plasma viscosity and thermography suggested increased activity and levels of C-reactive protein were unchanged. Functional improvements occurred mostly during the in-patient period. A wide range of complement levels was found but did not change, and IgG rheumatoid factor levels were negative throughout. The problems of laboratory assessment in AS are stressed.