IgM Rheumatoid Factor Levels Research Articles

Strong correlation in the serum levels of IgM rheumatoid factor and IgM anti-Chlamydia pneumoniae antibody

Strong correlation in the serum levels of IgM rheumatoid factor and IgM anti-Chlamydia pneumoniae antibody

Relationship of immunogenetic and immunologic markers and their influence on disease activity and radiological progression in patients with early rheumatoid arthritis

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Arthritis development in patients with arthralgia is strongly associated with anti-citrullinated protein antibody status: a prospective cohort study

BackgroundAnti-citrullinated protein antibodies (ACPA) are associated with increased risk for rheumatoid arthritis.ObjectiveTo investigate the effect of the presence and levels of ACPA on arthritis development in patients with arthralgia.MethodsPatients with...

Different properties of ACPA and IgM-RF derived from a large dataset: further evidence of two distinct autoantibody systems

IntroductionThe aim of this study was to examine seroconversion and the relationship with age and inflammation of autoantibodies in a large group of patients attending an outpatient rheumatology clinic.MethodsLevels of antibodies to citrullinated proteins/peptides (ACPAs) and IgM rheumatoid factor (IgM-RF) were determined in 22,427 samples collected from 18,658 patients. The diagnosis was derived from a diagnosis registration system. The degree of seroconversion in repeated samples and the correlation of levels with age and inflammatory markers were determined for ACPA and IgM-RF in rheumatoid arthritis (RA) and non-RA patients.ResultsSeventy-one percent of RA patients (n = 1,524) were ACPA-positive and 53% were IgM-RF-positive; in non-RA patients (n = 2,245), the corresponding values were 2% and 4%, respectively. In patients with at least two samples (n = 3,769), ACPA status was more stable than IgM-RF status in RA patients. ACPA- or IgM-RF-negative non-RA patients seldom became positive. ACPA positivity was unrelated to age in both RA and non-RA patients. IgM-RF positivity was unrelated to age in RA patients; however, it increased with age in non-RA patients. The correlation between autoantibody levels and inflammatory markers was low in general and was somewhat higher for IgM-RF than for ACPA.ConclusionsACPA status is more stable in time and with increasing age than IgM-RF status, further establishing its role as a disease-specific marker. ACPA and IgM-RF levels are only moderately correlated with markers of inflammation.

Immunogenetic and immunologic markers of early rheumatoid arthritis. RADIKAL program first stage results

Objective. To assess frequency of immunogenetic (HLA-DRB I allels) and immunologic - anti-cyclic citrullinated peptide antibodies (ACCP), IgM rheumatoid factor (RF) - parameters and their significance as markers of early rheumatoid arthritis (RA). Material and methods. HLA-DRB 1 alleles, ACCP and IgM RF were evaluated in 95 pts with early RA who fulfilled ACR criteria 1987 with disease duration 2 years or less. In 85,3% of them disease duration was <12 months. 135 blood donors without autoimmune diseases and relevant compromised inheritance. Basic low-resolving oligo-typing of HLA- DRB 1 gene and high-resolving oligo-typing of HLA-DRB 1*04 alleles was performed with multiplex polymerase chain reaction. ACCP2 and IgM RF levels were evaluated by immunoenzyme assay and nephelometric immunoassay with commercial kits. Results. Early RA group showed higher frequency of HLA-DRB 1 allele than control group (45,3% and 15,6% respectively, OR=4,5, 95% Cl 2,3-8,7). *05, *06 and *07 alleles in RA group were significantly less frequent than in control. *0401 allele was most frequent (25,3%) among HLA-DRB 1*04. Double dose SE+/SE+ (double set of any from *01,*0401, *0404, *0405, *0408, *10) was revealed in 33,7% of RA group pts and in 5,2% of cases in control group (OR=9,3, 95% Cl 3,7-24,6, p=lxl0 7). Absence of SE alleles (SE-/ SE-) in RA group was negatively associated with RA development (OR=0,28, 95% Cl 0,20, 5). In RA pts homozygote *0401/*0401 genotype was significantly more frequent among SE+/SE+ genotypes than in control group (17,8% and 1,5% respectively, OR=14,5, 95% Cl 3,1-93,4, p<0,0001). In RA group ACCP diagnostic level was revealed in 60,0% of cases, IgM RF — in 71,6% of cases. Most close relationship existed between ACCP and RF (r =0,66, p<0,05), less prominent — between SE and ACCP (r s=0,34, p<0,05). Correlation relationship between SE and RF was not revealed. In presence of at least one SE allele RF concentration was 280,4±414,3 lU/ml, in absence — 83,1 + 176,1 lU/ml (p<0,01). ACCP level in SE presence and absence was 56,2±44,6 lU/ml and 27,5±41,2 IU/ml respectively (p<0,01). Conclusion. HLA-DRB 1 (SE+) allele, ACCP and RF are significant markers of early RA development risk but ACCP and RF have diagnostic significance.

IgM rheumatoid factor in congenital syphilis: associations with clinical and laboratory findings

IgM rheumatoid factor (RF), measured by means of an ELISA, was detected in 92% of infants with congenital syphilis. Elevated levels were found to correlate with liver and renal involvement as well as the extent of the disease (P less than 0.05). In addition, levels of circulating immune complexes were closely related to the RF concentration (P less than 0.001). Following treatment of the infants both RF levels and VDRL titres declined at a similar rate (P less than 0.001). These findings indicated a close relationship between the disease process and IgM RF levels. It is postulated that IgM RF may add to immune complex deposition and exacerbate tissue damage in congenital syphilis.

Synovial tissue response to rituximab: mechanism of action and identification of biomarkers of response

Objective:To investigate the synovial tissue in patients with rheumatoid arthritis (RA) treated with rituximab and to identify possible predictors of clinical response.Methods:A total of 24 patients with RA underwent synovial...

Heterophilic antibody interference in a tryptase immunoassay

Objective Investigation of the susceptibility of a tryptase immunoassay to interference by heterophilic antibodies. Methods The effect of preincubation with a blocking agent was investigated on the levels of tryptase, human anti-mouse antibodies and IgM rheumatoid factor in sera with elevated IgM rheumatoid factor levels. Results In 5 of 30 sera with IgM rheumatoid factor, tryptase levels were reduced at least twofold after pre-incubation with blocking reagent. A significant association was observed between the presence of IgM rheumatoid factor in the sera and the interference of tryptase immunoassay. There was no quantitative correlation found between the reduction in serum tryptase level by treatment with a blocking agent, and the amount of IgM rheumatoid factor was present. However, this reduction in serum tryptase was significantly correlated with the amount of human anti-mouse antibodies in the sera. After incubation with blocking agent, there was no change in IgM Rheumatoid factor level, but a significant decrease in human anti-mouse antibodies. Conclusion The Phadia tryptase assay method, in its present form, is sensitive to interference by heterophilic antibodies.

Predictive Value of Antibodies to Citrullinated Peptides and Rheumatoid Factors in Anti‐TNF‐α Treated Patients

This article will focus on the relationship between serum levels of anti-citrullinated peptide antibodies (anti-CCP) or rheumatoid factor (RF) and clinical response to TNF-alpha blockers in order to evaluate whether these antibodies may have a role as serological markers of response to therapy in rheumatoid arthritis (RA). The changes induced in anti-CCP levels after TNF blocking therapy still remain a controversial issue even though a marked reduction following conventional DMARDs has been reported in early disease. On the other hand, a drop in RF levels during treatment has been reported by many authors. Decreased IgM RF levels seem to parallel clinical response suggesting that this antibody can also be regarded as a marker of response to treatment. Pre-treatment RF positivity or negativity does not influence response to TNF-alpha blocking therapy while high pre-treatment levels of IgA RF seem to be associated with a poor response rate.

Dissecting the heterogeneity of rheumatoid arthritis through linkage analysis of quantitative traits

To dissect the heterogeneity of rheumatoid arthritis (RA) through linkage analysis of quantitative traits, specifically, IgM rheumatoid factor (IgM-RF) and anti-cyclic citrullinated peptide (anti-CCP) autoantibody titers. Subjects, 1,002 RA patients from 491 multiplex families recruited by the North American RA Consortium, were typed for 379 microsatellite markers. Anti-CCP titers were determined based on a second-generation enzyme-linked immunosorbent assay, and IgM-RF levels were quantified by immunonephelometry. We used the Merlin statistical package to perform nonparametric quantitative trait linkage analysis. For each of the quantitative traits, evidence of linkage, with logarithm of odds (LOD) scores of >1.0, was found in 9 regions. For both traits, the strongest evidence of linkage was for marker D6S1629 on chromosome 6p (LOD 14.02 for anti-CCP and LOD 12.09 for RF). Six other regions with LOD scores of >1.0 overlapped between the 2 traits, on chromosomes 1p21.1, 5q15, 8p23.1, 16p12.1, 16q23.1, and 18q21.31. Evidence of linkage to anti-CCP titer but not to RF titer was found in 2 regions (chromosomes 9p21.3 and 10q21.1), and evidence of linkage to RF titer but not to anti-CCP titer was found in 2 regions (chromosomes 5p15.2 and 1q42.3). Several covariates were significantly associated with 1 or both traits, and linkage analysis exploring the covariate effects revealed striking effects of sex in modulating linkage signals for several chromosomal regions. For example, sex had a striking impact on the linkage results for both quantitative traits on chromosome 6p (P = 0.0007 for anti-CCP titer and P = 0.0012 for RF titer), suggesting a sex-HLA region interaction. Analysis of quantitative components of RA is a promising approach for dissecting the genetic heterogeneity of this complex disorder. These results highlight the potential importance of sex or other covariates that may modulate some of the genetic effects that influence the risk of specific disease manifestations.

Is measurement of IgM and IgA rheumatoid factors (RF) in juvenile rheumatoid arthritis clinically useful?

The prevalence and clinical relevance of IgM and IgA RF detected by ELISA were studied in 91 patients with juvenile rheumatoid arthritis (JRA) and 45 healthy children. IgM and IgA RF were detected, respectively, in 33 and 44% of the patients, compared to 6.7 and 15.6% of the healthy children (p = 0.001 and 0.0006, respectively). The frequency of IgM RF was significantly higher in patients with polyarticular (52%) as compared to systemic onset JRA (21%; p = 0.04). Five out of ninety-one patients and none of the control group were IgM RF positive by the latex test. High levels of IgM RF were detected more frequently in patients with active disease (p = 0.01) and positive latex agglutination test (p < 0.001) and had a marginally significant association with severe radiological deformities (p = 0.05). The presence of IgA RF was associated with active disease in polyarticular onset JRA children (p = 0.04). In conclusion, high levels of IgM RF and the detection of IgA RF can be useful in assessing clinical activity in a subset of patients with JRA.

Vascular and neurological considerations in rheumatoid arthritis

Rheumatoid arthritis is a chronic systemic inflammatory disease characterized by a symmetrical polyarthritis of varying extent, severity and deformity. It is associated with synovitis of joint and tendon sheaths, articular cartilage loss, and punched out erosions of peri-articular bone. Most patients have elevated blood levels of IgM rheumatoid factor.

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.

Antibodies against cyclic citrullinated peptides in patients affected by rheumatoid arthritis before and after infliximab treatment

To evaluate antibodies against cyclic citrullinated peptides (anti-CCP) together with rheumatoid factor (RF), antinuclear antibodies (ANA) and C-reactive protein (CRP), in patients affected by rheumatoid arthritis (RA), before and after infliximab treatment. Twenty-seven patients (five men and 22 women, mean age of 51.9 years, mean duration of disease 12.6 years) affected by RA, refractory to conventional DMARDs, were treated with infliximab, at the conventional dosage. Before starting infliximab and after 22 weeks, on the occasion of the fifth infusion, anti-CCP antibodies were tested by ELISA method. At the same time IgM RF, ANA and CRP level were measured. Before infliximab therapy, anti-CCP antibodies resulted positive in 23 patients (85.1%); the serum level did not change after infliximab treatment; only one case negative at baseline became slightly positive after treatment. Before and after therapy RF resulted positive in 22 cases (81.4%) and 21 cases (77.7%) respectively; comparing values at baseline with those after 22 weeks of treatment with infliximab, RF levels significantly decreased, as well as CRP values. In contrast to both anti-CCP antibodies, which remained stable, and to RF, which fell after infliximab, ANA were positive > or = 1: 160 in four cases at baseline and in 12 after treatment. The titre of anti-CCP antibodies did not significantly change after anti-TNFalpha blocker administration; instead the positivity of RF significantly decreased. As opposed to antinuclear and anti-dsDNA antibodies, which may appear or increase in titre during infliximab treatment, the typical autoantibodies detectable in RA show a different trend; in fact, anti-CCP antibodies remained stable and RF decreased.

Association of rheumatoid arthritis treatment response and disease duration with declines in serum levels of IgM rheumatoid factor and anti–cyclic citrullinated peptide antibody

To examine the association of treatment response and disease duration with changes in rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibody levels among patients with rheumatoid arthritis (RA). The study sample included 66 RA patients who completed double-blind, randomized clinical protocols and for whom baseline and followup serum samples were available. Anti-CCP and RF levels were measured using commercially available assay kits. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to describe the association of response and disease duration with declines in antibody levels. Patients had a mean +/- SD age of 49.9 +/- 12.0 years and were predominantly female (n = 51; 77%). The mean +/- SD duration between the times at which the baseline and followup serum samples were obtained was 13.7 +/- 8.6 months. Among the 64 subjects with positive antibody at baseline, 33 (52%) experienced a > or =25% reduction in the anti-CCP antibody level during the course of treatment, and 35 patients (55%) had a > or =25% reduction in RF. After adjustment for the baseline anti-CCP antibody level, only a shorter disease duration (< or =12 months) was significantly associated with a decline in the level of anti-CCP antibody (OR 3.0, 95% CI 1.0-8.8), and no association with treatment response was observed. Conversely, treatment response was the only significant determinant of a decrease in RF levels (OR 3.6, 95% CI 1.2-10.4). Shorter disease duration predicts greater declines in anti-CCP antibody levels with treatment in RA. Although treatment response is a robust determinant of a decrease in RF, it does not appear to be associated with declines in the anti-CCP antibody level.

Antineutrophil cytoplasmic antibodies in Bulgarian patients with rheumatoid arthritis: characterization and clinical associations

The aim of this study was to study the prevalence, subspecificities, and immunoglobulin (Ig)G subclass distribution of antineutrophil cytoplasmic antibodies (ANCA) in 90 Bulgarian patients with rheumatoid arthritis (RA) and to investigate the clinical associations of ANCA in these patients. The ANCA were detected by indirect immunofluorescence, while antigen specificities were determined by enzyme-linked immunosorbent assay (ELISA) directed against myeloperoxidase (MPO), proteinase 3 (PR3), bactericidal/permeability-increasing protein (BPI), lactoferrin (LF), leukocyte elastase (LE), and cathepsin G (CG). The IgG subclass reactivity of antibodies to BPI and LF was measured. Antineutrophil cytoplasmic antibodies were found in 18 RA patients. Only a P-ANCA fluorescence pattern was seen. Six sera reacted to BPI, five to LF, one to MPO, one to PR3, and one to CG by ELISA testing. Immunoglobulin-G1 was the predominant subclass for LF-ANCA, whereas IgG1/3 contributed mainly to BPI-ANCA. Compared to P-ANCA-negative RA patients, the P-ANCA-positive patients exhibited significantly higher inflammatory activity, as estimated by disease activity score, C-reactive protein, erythrocyte sedimentation rate, and higher levels of IgM rheumatoid factor. Twenty percent of Bulgarian patients with RA have P-ANCA in their sera. These antibodies are directed against variable antigen specificities, while ANCA positivity in RA reflects disease and inflammatory activity.

Rheumatoid arthritis is already expensive during the first year of the disease (the Swedish TIRA project).

To calculate direct and indirect costs in early rheumatoid arthritis (RA) and to characterize patients generating high and low costs respectively. Two hundred and ninety-seven patients with recent-onset (< or = 12 months) RA were recruited. Clinical/laboratory data and 'health assessment questionnaire' (HAQ) were registered at inclusion and after 3, 6 and 12 months. After 6 and 12 months, the patients completed a questionnaire concerning health-care utilization and days lost from work. A cut-off point for direct costs was set at 34,000 Swedish kronor (euro3675) defining one-third of the patients as a high-cost group and two-thirds as low-cost group. Indirect costs were calculated for patients aged <65 yr. Two hundred and eleven patients completed the HAQ on both occasions. Indirect costs exceeded direct costs by a factor of 2.3. Sixty three per cent experienced work disability during the first year and were identified as the 'high-indirect-cost group'. Indirect costs accounted for >70% of total costs. Direct costs included ambulatory health care (76%), hospitalization (12%) and medication (9%). Men aged > or = 65 yr had low costs compared with younger men and women of all ages. In multiple logistic regression tests, HAQ, high levels of IgM rheumatoid factor (IgM RF) and poor hand function increased the odds of entering the high-direct-cost group, and poor hand function and pain increased the odds of entering the high-indirect-cost group. Substantial costs were incurred during the first year after diagnosis of early RA, mainly due to work disability. Indirect costs were two to three times higher than direct costs. High levels of IgM RF, high HAQ score, poor hand function and pain increased the odds of entering high-cost groups.

Tissue Transglutaminase Autoantibodies in Patients with IgM Rheumatoid Factors

The recent identification of tissue transglutaminase (tTG) as the autoantigen for celiac disease-associated anti-endomysial antibodies (EMA) has allowed the use of rapid immunoassay to detect the presence of autoantibodies, anti-tTG, in the serum of patients. In this study, we examined the prevalence of IgG or IgA anti-tTG in sera from patients with elevated levels of IgM rheumatoid factors, which are autoantibodies reactive with the Fc portion of IgG. We report here on four cases of anti-tTG positivity for patients with elevated IgM rheumatoid factor (RF) without evidence of celiac sprue. The study population consisted of 65 patients (26 men, 39 women; mean age, 49 years; range 4 - 92 years) with elevated RF (>20 U/ml ), and 23 healthy subjects (12 men, 11 women; mean age, 46 years; range, 21 - 54 years). IgG and IgA anti- tTG levels were detected using a commercially available ELISA kit (Immuno-Biological Laboratories, Germany). Out of 65 patients, one (1.5%) and three (4.6%) patients were positive for IgG and IgA anti-tTG antibodies, respectively, and this was a higher frequency than occurred in healthy subjects (0/23). The clinical features of the four cases positive for IgG or IgA anti-tTG were as follows: The first case (female, 63 yrs) positive for IgA anti-tTG antibody suffered from rheumatoid arthritis, type II diabetes mellitus, iron deficiency anemia and gastric indigestion without symptoms of malabsorption. She denied any gluten sensitivity on her diet. Her esophagogastroduodenoscopic biopsy showed mucosal atrophy with no elongated crypts or infiltration of inflammatory cells in the lamina propria. The remaining three cases positive for anti-tTG antibodies had interstitial pneumonia, a herniated lumbar disc, and mild scoliosis, respectively. They all denied any malabsorption symptoms or gluten sensitivity. Jejunal biopsy could not be performed in all four cases.

Development of internal controls for the Luminex instrument as part of a multiplex seven-analyte viral respiratory antibody profile.

The ability of the Luminex system to simultaneously quantitate multiple analytes from a single sample source has proven to be a feasible and cost-effective technology for assay development. In previous studies, my colleagues and I introduced two multiplex profiles consisting of 20 individual assays into the clinical laboratory. With the Luminex instrument's ability to classify up to 100 distinct microspheres, however, we have only begun to realize the enormous potential of this technology. By utilizing additional microspheres, it is now possible to add true internal controls to each individual sample. During the development of a seven-analyte serologic viral respiratory antibody profile, internal controls for detecting sample addition and interfering rheumatoid factor (RF) were investigated. To determine if the correct sample was added, distinct microspheres were developed for measuring the presence of sufficient quantities of immunoglobulin G (IgG) or IgM in the diluted patient sample. In a multiplex assay of 82 samples, the IgM verification control correctly identified 23 out of 23 samples with low levels (<20 mg/dl) of this antibody isotype. An internal control microsphere for RF detected 30 out of 30 samples with significant levels (>10 IU/ml) of IgM RF. Additionally, RF-positive samples causing false-positive adenovirus and influenza A virus IgM results were correctly identified. By exploiting the Luminex instrument's multiplexing capabilities, I have developed true internal controls to ensure correct sample addition and identify interfering RF as part of a respiratory viral serologic profile that includes influenza A and B viruses, adenovirus, parainfluenza viruses 1, 2, and 3, and respiratory syncytial virus. Since these controls are not assay specific, they can be incorporated into any serologic multiplex assay.

Is rheumatoid arthritis in African descendants from North and South America the same?

RHEUMATOID ARTHRITIS (RA) is known to occur worldwide but not with the same frequency or degree of severity among various population groups. These differences have been related to the uneven distribution of the rheumatoid epitope and the HLA-DR alleles carrying it, although other genes acting alone or in conjunction with the rheumatoid epitope (polymorphisms of tumor necrosis factor alpha, T-cell receptors, Fcgamma receptor IIIA, and interferon gamma, for example) as well as nongenetic factors may be important determinants of the predisposition to RA and to its severity (1-7). Some populations with a relatively low frequency of the rheumatoid epitope are known to have a relatively mild disease; such is the case for Caucasians from the Mediterranean basin and their descendants elsewhere in the world (8-15). In contrast, African descendants from North America, who also have a low frequency of the rheumatoid epitope, have a disease as severe as that of the Caucasians from the same geographic area (16,17). The study by Anaya et al in this issue of the journal (18) includes 2 Colombian subpopulations, one of African descendants from Quibdo and the other of Mestizos (an admixture of the original inhabitants of the region and Spanish conquistadors) from Medellin. The investigators studied with some detail the Quibdo patients, characterizing their clinical and immunogenetic features. The Medellin patients, attending a rheumatology clinic at a general hospital, served as a frame of reference to indicate that in fact patients with erosive RA are being seen in Colombia. There are 2 obvious angles to this report: the first is the comparison between the RA patients from the 2 Colombian ethnic groups and the second is the comparison between the Quibdo African descendants (“African Colombians”) and the African descendants from North America (“African Americans”). In both cases the report posits more questions than provides answers. Given the different methodologies used to study the 2 Colombian populations (case ascertainment and clinical and immunogenetic characterization), I have chosen to concentrate my comments on the 2 populations of African ancestry, the one from Quibdo reported in the Anaya article (18) and the one from the United States studied by McDaniel et al several years ago (16). The African Colombian patients had in general a relatively mild disease as evidenced by the paucity of erosions and low levels of IgM-rheumatoid factor (18). These findings are in clear contrast with the patients from the U.S. whose disease was as severe as that of Caucasians from the same geographic area (16). The African Colombian patients also carried the rheumatoid epitope sparingly (as did a small number of local controls); the investigators then concluded that the infrequency of the rheumatoid epitope was probably the reason for the mild disease observed in their Africandescendant patients, pointing out that this is probably not the sole explanation. I concur with their assessment, as the rheumatoid epitope also was found to be infrequent among the African Americans studied by McDaniel et al (16). If in fact African descendants in South America had a much milder disease than those in North America (granted, this is only 1 study in a relatively small community of African descendants in 1 South American country), were the phenotypic differences observed real or artifactual (since the methods used to study these 2 populations are different and thus not directly comparable)? (19).