Presence Of IgM Rheumatoid Factor Research Articles

Accuracy and tolerability of self-sampling of capillary blood for analysis of inflammation and autoantibodies in rheumatoid arthritis patients—results from a randomized controlled trial

BackgroundRheumatoid arthritis (RA) requires early diagnosis and tight surveillance of disease activity. Remote self-collection of blood for the analysis of inflammation markers and autoantibodies could improve the monitoring of RA and facilitate the identification of individuals at-risk for RA.ObjectiveRandomized, controlled trial to evaluate the accuracy, feasibility, and acceptability of an upper arm self-sampling device (UA) and finger prick-test (FP) to measure capillary blood from RA patients for C-reactive protein (CRP) levels and the presence of IgM rheumatoid factor (RF IgM) and anti-cyclic citrullinated protein antibodies (anti-CCP IgG).MethodsRA patients were randomly assigned in a 1:1 ratio to self-collection of capillary blood via UA or FP. Venous blood sampling (VBS) was performed as a gold standard in both groups to assess the concordance of CRP levels as well as RF IgM and CCP IgG. General acceptability and pain during sampling were measured and compared between UA, FP, and VBS. The number of attempts for successful sampling, requests for assistance, volume, and duration of sample collection were also assessed.ResultsFifty seropositive RA patients were included. 49/50 (98%) patients were able to successfully collect capillary blood. The overall agreement between capillary and venous analyses for CRP (0.992), CCP IgG (0.984), and RF IgM (0.994) were good. In both groups, 4/25 (16%) needed a second attempt and 8/25 (32%) in the UA and 7/25 (28%) in the FP group requested assistance. Mean pain scores for capillary self-sampling (1.7/10 ± 1.1 (UA) and 1.9/10 ± 1.9 (FP)) were significantly lower on a numeric rating scale compared to venous blood collection (UA: 2.8/10 ± 1.7; FP: 2.1 ± 2.0) (p=0.003). UA patients were more likely to promote the use of capillary blood sampling (net promoter score: +28% vs. −20% for FP) and were more willing to perform blood collection at home (60% vs. 32% for FP).ConclusionsThese data show that self-sampling is accurate and feasible within one attempt by the majority of patients without assistance, allowing tight monitoring of RA disease activity as well as identifying individuals at-risk for RA. RA patients seem to prefer upper arm-based self-sampling to traditional finger pricking.Trial registrationDRKS.de Identifier: DRKS00023526. Registered on November 6, 2020.

Anti-CCP antibodies and rheumatoid factor in systemic sclerosis: Prevalence and relationships with joint manifestations

It is known that anti-citrullinated protein (a-CCP) antibodies and rheumatoid factor (RF) can be present in systemic sclerosis (SSc) patients, particularly with joint involvement. The aim of the study was to assess the prevalence of a-CCP antibodies and immunoglobulin M class (IgM) RF, and the relationships between their presence and joint manifestations in patients with SSc. The study included 100 European Caucasian SSc patients hospitalized consecutively in the Department of Rheumatology and Connective Tissue Diseases (Lublin, Poland). Anti-citrullinated protein antibodies and IgM RF were determined using a commercial enzyme-linked immunosorbent assay (ELISA) test. Anti-citrullinated protein antibodies were found in 10 out of 100 (10%) SSc patients and IgM RF in 71 out of 100 (71%) SSc patients. In the study, 90/100 (90%) SSc patients had joint manifestations (arthralgia or arthritis), 34/100 (34%) had arthritis and 6/100 (6%) had a systemic sclerosis-rheumatoid arthritis (SSc-RA) overlap syndrome. Significantly higher a-CCP antibody levels (p = 0.012), erythrocyte sedimentation rate (ESR) (p = 0.029) and C-reactive protein (CRP) levels (p = 0.020) were observed in the SSc group with arthritis. A significant correlation was found between the group with arthritis and the presence of a-CCP antibodies, and between the arthralgia group and the presence of IgM RF. The prevalence of RF and a-CCP antibodies is relatively high in SSc, and joint involvement occurs frequently. There was a significantly higher prevalence of IgM RF in the group with joint manifestations. About 1/3 of SSc patients had symptoms of arthritis. Arthritis is connected with the presence of a-CCP antibodies, while arthralgia is connected with the presence of IgM RF.

Lack of correlation between IL-21 and type I IFN signature suggests different roads to pathogenesis in Rheumatoid Arthritis

Event Abstract Back to Event Lack of correlation between IL-21 and type I IFN signature suggests different roads to pathogenesis in Rheumatoid Arthritis Rachel Ettinger1*, Jodi Karnell1, Christopher A. Morehouse1, Ethan Grant1, Devon Taylor1, Mildred Wilson2, Raphaela Goldbach-Mansky2, Yihong Yao1, Ronald Herbst1 and Laura Carter1 1 MedImmune, LLC, Research, United States 2 NIH, NIAMS, United States IL-21 and IFNa are increased in several autoimmune syndromes including Rheumatoid Arthritis (RA). These cytokines have pleiotropic actions on cell types of lymphoid and non-lymphoid origin and both have been reported to induce plasma cell differentiation. In a cohort of RA patients (n=42), we tested if a correlation exists between IL-21 and type I IFN (IFN) and how these cytokines segregate with particular autoantibodies and immunologic mediators. In ~50% of the RA patients examined, IL-21 serum levels were elevated (up to ~500 pg/ml) vs. the majority of normal individuals under 20 pg/ml (n=30/31). Increased IL-21 was not part of general cytokine activation, as only 8/97 analytes measured associated significantly with increased IL-21 levels. Strikingly, a tight correlation existed between IL-21 levels and the presence of IgM Rheumatoid Factor (RF) p=0.0003 as well as to cyclic citrullinated peptide autoantibodies (CCP) p=0.0155, but not to anti-ss or -dsDNA Ab titers in which only 6/42 and 5/42, respectively of RA had titers. In this RA cohort, ~20% of the patients had a 4-gene IFN signature of whole blood. Importantly, there was no correlation between increased IL-21 levels and IFN signature score. IFN signature score was independent of RF or anti-CCP titers, but correlated to ssDNA autoantibody titers p=0.0367 and trended towards an association with anti-dsDNA autoantibody titers. These data suggest that while both IL-21 and IFN are believed to be involved in the pathogenesis of rheumatic disease, these pathways do not appear to intersect in RA patients, and may represent distinct targets for disease intervention. Keywords: IL-21, IFNa, rheumatoid arthritis (RA), dsDNA Ab, Autoantibody, CCP Ab Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Translational immunology and immune intervention Citation: Ettinger R, Karnell J, Morehouse CA, Grant E, Taylor D, Wilson M, Goldbach-Mansky R, Yao Y, Herbst R and Carter L (2013). Lack of correlation between IL-21 and type I IFN signature suggests different roads to pathogenesis in Rheumatoid Arthritis. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00653 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 12 Jun 2013; Published Online: 22 Aug 2013. * Correspondence: Dr. Rachel Ettinger, MedImmune, LLC, Research, Gaithersburg, MD, 20878, United States, ettingerc@medimmune.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Rachel Ettinger Jodi Karnell Christopher A Morehouse Ethan Grant Devon Taylor Mildred Wilson Raphaela Goldbach-Mansky Yihong Yao Ronald Herbst Laura Carter Google Rachel Ettinger Jodi Karnell Christopher A Morehouse Ethan Grant Devon Taylor Mildred Wilson Raphaela Goldbach-Mansky Yihong Yao Ronald Herbst Laura Carter Google Scholar Rachel Ettinger Jodi Karnell Christopher A Morehouse Ethan Grant Devon Taylor Mildred Wilson Raphaela Goldbach-Mansky Yihong Yao Ronald Herbst Laura Carter PubMed Rachel Ettinger Jodi Karnell Christopher A Morehouse Ethan Grant Devon Taylor Mildred Wilson Raphaela Goldbach-Mansky Yihong Yao Ronald Herbst Laura Carter Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Inflammation and autoantibody markers identify rheumatoid arthritis patients with enhanced clinical benefit following rituximab treatment

Rituximab significantly improves the signs and symptoms of rheumatoid arthritis (RA) and slows the progression of joint damage. The aim of this study was to identify clinical characteristics and biomarkers that identify patients with RA in whom the clinical benefit of rituximab may be enhanced. The study group comprised 1,008 RA patients from 2 independent randomized placebo-controlled phase III clinical trials (REFLEX [Randomized Evaluation of Long-Term Efficacy of Rituximab in Rheumatoid Arthritis] and SERENE [Study Evaluating Rituximab's Efficacy in Methotrexate Inadequate Responders]). A novel threshold selection method was used to identify baseline candidate biomarkers present in at least 20% of patients that enriched for placebo-corrected American College of Rheumatology 50% improvement (ACR50 response; a high clinical efficacy bar) at week 24 after the first course of rituximab. The presence of IgM rheumatoid factor (IgM-RF), IgG-RF, IgA-RF, and IgG anti-cyclic citrullinated peptide (anti-CCP) antibodies together with an elevated C-reactive protein (CRP) level were associated with enhanced placebo-corrected ACR50 response rates in the REFLEX patients with RA who had an inadequate response to anti-tumor necrosis factor therapies. These findings were independently replicated using samples from patients in SERENE who had an inadequate response to disease-modifying antirheumatic drug treatment. The combination of an elevated baseline CRP level together with an elevated level of any RF isotype and/or IgG anti-CCP antibodies was further associated with an enhanced benefit to rituximab. The presence of any RF isotype and/or IgG anti-CCP autoantibodies together with an elevated CRP level identifies a subgroup of patients with RA in whom the benefit of rituximab treatment may be enhanced. Although the clinical benefit of rituximab was greater in the biomarker-positive population compared with the biomarker-negative population, the clinical benefit of rituximab compared with placebo was also clinically meaningful in the biomarker-negative population.

Relative Clinical Influence of Clinical, Laboratory, and Radiological Investigations in Early Arthritis on the Diagnosis of Rheumatoid Arthritis. Data from the French Early Arthritis Cohort ESPOIR

To evaluate the relative level of influence of usual investigations in early arthritis on the diagnosis of rheumatoid arthritis (RA). those included in the ESPOIR early arthritis cohort, a national cohort of patients with grade ≥ 2 synovitis for > 6 weeks and < 6 months. The diagnostic properties of variables assessed at baseline were measured against the diagnosis of RA defined by American College of Rheumatology criteria (at any timepoint between inclusion and 12-month followup) and expert opinion. Various models, including (1) clinical data; (2) clinical + radiographic data (plain radiographs); (3) addition of rheumatoid factor (RF) and/or anti-cyclic citrullinated peptide (anti-CCP); and (4) addition of HLA-DR typing, were assessed by comparing areas under the curves for ROC curves. Of 731 patients studied, 372 (50.9%) satisfied criteria for RA at 1 year. In univariate analysis, sensitivity was highest for distal articular presentation (94.6%), presence of IgM RF (69.4%), pain on metatarso-phalangeal squeeze test (66.1%), and presence of anti-CCP (65.6%); whereas specificity was highest for nodules (100%), HLA typing: shared-epitope double dose (95.9%), radiographic erosions (86.5%), and anti-CCP antibodies (86.4%). The most efficient model included swollen joint count, morning stiffness, erosions, RF, and anti-CCP. Adding rheumatoid nodules, C-reactive protein, or HLA-DR information was not contributive. In addition to the clinical variables and radiographs, RF and/or anti-CCP are the single variables of interest that are contributive for the diagnosis of RA.

Relationship Between Rheumatoid Factor Isotypes and IgG Anti-Cyclic Citrullinated Peptide Antibodies

To validate in a general patient population (GPP) the clinical value of measuring rheumatoid factor (RF) isotypes in relationship to IgG anti-cyclic citrullinated peptide (CCP) antibodies (CCP2 and CCP3). Serum samples were obtained as follows: 1021 GPP, for whom RF was ordered for diagnosis, 137 with rheumatoid arthritis (RA), 100 healthy blood donors (HBD), and 50 with systemic lupus erythematosus. Turbidimetry and ELISA were utilized for RF screening, and individual RF isotypes and IgG anti-CCP antibodies were measured by ELISA; RF IgG was measured after pepsin digestion. We validated the generally accepted 90%-98% positive predictive value (PPV) and about 68% sensitivity of the anti-CCP2 test on our diagnosed cohorts as 96% (95% CI 89-99) and 65% (95% CI 56-73), respectively. The 282 RF IgM+ specimens identified in the GPP were subdivided into 3 subsets: (1) 83 as RF IgM+ IgG+ IgA+ with 63% (95% CI 51-73) anti-CCP2+ (i.e., sensitivity similar to the RA cohort); (2) 50 as RF IgM+ IgG- IgA+ with significantly fewer anti-CCP2+ (22%; 95% CI 12-36); and (3) about half as IgM+ IgG- IgA- with just 3% (95% CI 1-8) anti-CCP2+, i.e., not significantly different from the 1% (95% CI 0-5) in HBD. Thus, the chance for a specimen in the GPP to be anti-CCP2+ (i.e., to come from an RA patient) was increased by 7- and 21-fold, respectively, by identifying RF IgA and IgG in addition to IgM. About one-third of anti-CCP- RA patients in our cohort were RF IgM+ IgG+ IgA+, reflected as 3.4% in the anti-CCP2- GPP. The agreement between anti-CCP2 and anti-CCP3 was significantly higher for RF+ RA and GPP patients, 86% (95% CI 78-93) and 83% (95% CI 73-91), respectively, than for the RF- RA (27%; 95% CI 6-61), RF- GPP (4%; 95% CI 0-19), and non-RA controls. Anti-CCP2 but not anti-CCP3 significantly distinguished the HBD from the GPP (95% CI). Measurement of the 3 isotypes of RF may increase by 7- to 21-fold the chance of making the serologic diagnosis of RA; a testing algorithm is proposed. The anti-CCP antibody response appears significantly less peptide-specific in the presence of IgM RF than in its absence.

Deterioration of lung function is associated with presence of IgM rheumatoid factor and smoking in patients with systemic sclerosis

Smoking is a known risk factor for the development of several lung diseases, autoimmune diseases, and IgM rheumatoid factor (RF) in nonrheumatic persons. In patients with rheumatoid arthritis and IgM RF the diffusion capacity is decreased in smokers but not in nonsmokers. In the present study of patients with systemic sclerosis (SSc) the influence of smoking and IgM RF on the lung function was calculated. One hundred fifty-five persons with SSc had vital capacity (VC) and diffusing capacity (DLco) measured at least twice with at least 1-year interval as percents of predicted values according to gender, age, height, and weight. The yearly changes in VC and DLco were calculated, Delta VC and Delta DLco, respectively. IgM RF was measured at the beginning of the study. Smoking was defined as having ever smoked. Statistically significant deterioration of VC and DLco in patients with circulating IgM RF was found only in smokers or previous smokers, P = 0.007 and P = 0.01, respectively. These findings were confirmed by means of multiple regression analyses. The presence of IgM RF in smoking SSc patients is associated with deteriorating lung function. Whether this is a causal association and whether the presence of IgM RF in smoking patients with SSc actually confers an increased risk of pulmonary damage remains to be determined.

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.

Autoantibodies in rheumatoid arthritis: association with severity of disease in established RA

Autoantibodies in rheumatoid arthritis (RA) are useful both for diagnosis and prognosis. Antibodies directed against citrullinated antigens have recently been shown to predict development of RA as well as poor outcome in early arthritis. Data on their role in established RA is limited. We studied the association of various autoantibodies in RA with its severity. A total of one hundred and twenty nine-patients with established RA was enrolled and sera were collected and stored at -70 degrees C. Data regarding erosions, deformities, and extra-articular features were collected. IgM rheumatoid factor (RF) was measured using nephelometry and value above 20 U was considered positive. IgA RF was measured by enzyme-linked immunosorbent assay (ELISA) and value above the mean+/-2 SD of normal healthy control was taken as positive. Anti-keratin antibody (AKA) was detected by indirect immunofluorescence assay using rat esophagus as substrate. Anti-cyclic citrullinated peptide (CCP) antibodies were measured by commercial ELISA and a value above 5 U was considered as positive. The prevalence of various autoantibodies was: IgM RF 82.2%, anti-CCP antibodies 82.2%, AKA 51.9%, and anti IgA RF 45%. The concordance rate of anti-CCP antibodies with IgM RF was 83%, with AKA 68%, and with IgA RF 60.5%. All but one patient positive for AKA were positive for anti-CCP antibodies. The presence of IgM RF, AKA, and anti-CCP antibody was associated with joint erosions and deformities. None of the antibodies had any association with presence of extra-articular features. No association of IgA RF was seen with erosions, deformities, or extra-articular features. Among 23 seronegative RA patients, 11 were positive for anti-CCP antibodies and 6 were AKA positive. The presence of anti-CCP antibodies was associated with presence of deformities (p<0.05). Anti-CCP antibodies are present in majority of patients with established RA including seronegative patients. Both anti-CCP and AKA, in addition to conventional marker like IgM RF, are associated with severe erosive disease.

Young age of onset is associated with increased prevalence of circulating IgM rheumatoid factor and antinuclear antibodies at presentation in women with rheumatoid arthritis.

In 200 patients, 143 women and 57 men, with rheumatoid arthritis (RA), age at onset was related to the presence of IgM rheumatoid factor (RF) and antinuclear antibodies (ANA) in serum at presentation. The patients were stratified into bands of age at onset: <40 years, 40- 60 years, and >60 years. In women, the prevalences of ANA (1:160) were 63.0%, 45.5%, and 31.1% in the respective age bands ( p=0.002), and the prevalences of IgM RF were 85.2%, 72.7% and 66.4%, respectively ( p=0.03). The prevalences of ANA and IgM RF among men were, respectively, 35% and 86% with no association with age at onset. The findings may indicate interactive effects between gender and various pathogenetic factors.

Evaluation of an IgM-specific indirect enzyme-linked immunosorbent assay for serodiagnosis of bovine respiratory syncytial virus infection: influence of IgM rheumatoid factor on test results with field sera.

A commercially available indirect enzyme-linked immunosorbent assay for measuring bovine respiratory syncytial virus (BRSV)-specific IgG was adapted to measure virus-specific IgM. Using this assay, the development of rapid IgM responses in experimentally infected calves was observed 7-9 days postinfection, with peak absorbance values ranging from 1.698 to 2.873. When absorbance values were expressed as a percentage of a positive reference serum, a positive/negative threshold of 22% was determined by testing serum samples from 59 healthy 3-5-month-old calves. Acute and convalescent serum samples collected from 151 calves during 38 outbreaks of respiratory disease were tested, and 130 sera were positive. To determine the number of false-positive results due to the presence of IgM rheumatoid factor, a method for depleting serum IgG by pretreatment of sera with a suspension of protein-G-agarose was developed. All sera that initially tested IgM positive were retested following depletion of serum IgG. False-positive IgM reactions were detected in 23 sera (17.7%). Specific IgM responses were confirmed in 107 sera from 84 calves. Evidence of BRSV infection was detected in 34 of 38 outbreaks. In contrast, seroconversion was detected in 69 calves from 24 outbreaks, confirming the diagnostic potential of the IgM assay. Overall correlation between IgM and seroconversion results was 74.2%. Intra- and interassay reproducibility were 12.50% and 17.48%, respectively (mean coefficients of variation).

IgM rheumatoid factor estimation by ELISA in seronegative rheumatoid arthritis before and after IgM fractionation: does seronegative RA exist?

We looked for the presence of IgM rheumatoid factor (RF) using an enzyme-linked immunosorbent assay (ELISA) in 25 patients with active seronegative rheumatoid arthritis. In unfractionated sera, 12 patients (48%) were positive for IgM RF (classical), but after IgM fractionation of 23 samples (2 samples were not available) using high performance liquid chromatography for fractionating IgM, 12 patients were positive for RF by ELISA indicating the presence of hidden RF. Finally, three patients were labelled as truly seronegative for IgM RF. Classical IgM RF as detected by ELISA correlated significantly with erosive disease. Hidden RF did not correlate with disease activity or severity in this cross-sectional study, and though its presence was associated with shorter disease duration this did not reach statistical significance.

Heterogeneity of disease phenotype in monozygotic twins concordant for rheumatoid arthritis.

The objective of the study was to investigate the genetic contribution to the clinical expression of rheumatoid arthritis (RA) by comparison of disease features in RA-concordant monozygotic (MZ) twin pairs. Fourteen RA-concordant MZ twin pairs recruited from a nation-wide study were examined to determine the degree of similarity in: (a) age of disease onset; (b) pattern of joint involvement; (c) pattern of extra-articular disease; (d) toxic reactions to drugs; (e) disease course; and (f) serology for rheumatoid factor (RF) and antinuclear antibody. There was considerable within-pair diversity in the variables studied. Some similarity within twin pairs was observed for the ages at disease onset (R = 0.63), presence of erosive changes (kappa = 0.61) and the presence of IgM RF (R = 0.87). No important similarity was seen, however, in the pattern of joint involvement, the occurrence of extra-articular disease, adverse drugs reactions, clinical disease course and reported disability level. There is heterogeneity in the genetic contribution to the clinical expression of RA. The overall lack of similarity for the majority of clinical variables indicates the importance of non-genetic factors on the expression of disease.

Serum IgM rheumatoid factor by enzyme-linked immunosorbent assay (ELISA) delineates a subset of patients with deforming joint disease in seronegative juvenile rheumatoid arthritis.

Using human IgG as an antigen in an enzyme-linked immunosorbent assay (ELISA), we looked for the presence of IgM rheumatoid factor (RF) in the sera of 74 children with juvenile rheumatoid arthritis (JRA). Nine children had RF detectable by both latex agglutination and ELISA. Forty-five percent (26 of 65) of the children who were seronegative by latex agglutination were found to be positive for IgM RF by ELISA. The prevalence of IgM RF was higher in patients with polyarticular onset disease (57.4%) than in those with pauciarticular onset (38.5%) or systemic onset (27.2%) disease. The prevalence of RF was higher in sera from patients with deforming joint disease than those without deformities (P < 0.01).

Age specific prevalence of antibodies against Chlamydia pneumoniae in Iceland.

Chlamydia pneumoniae is a newly recognized common cause of respiratory tract infections. The aim of this study was to examine its prevalence in Iceland. The study was based on 1020 serum samples from individuals 0-99 years old. The samples were divided into 10-year age groups. IgG and IgM antibodies were determined with microimmunofluorescence assay. An IgG titer > or = 32 and IgM titer > or = 16 were considered positive. The prevalence of positive IgG titer in the study population was 53 +/- 16% (mean +/- SD, age group range 14-66%). Neither seasonal nor gender-based difference in IgG antibody prevalence was demonstrated. It was lowest in the youngest group, 0-9 years old (p < 0.001), but rose linearly to age 70 (p < 0.005). 34 samples were IgM positive on initial testing; most from the older age groups. 12 were rheumatoid factor positive as well. After treatment with caprine antihuman IgG antibodies all became negative. The prevalence of C. pneumoniae infections is high in Iceland according to these results and similar to that in neighbouring countries. The presence of IgM rheumatoid factor may cause false positive tests for pathogen-specific IgM by immune complex binding with pathogen-specific IgG, thereby requiring its removal before testing.

Low and high molecular weight cytomegalovirus-specific immunoglobulin M antibody in renal transplant patients with cytomegalovirus infections.

Sera from 27 renal transplant patients with primary and recurrent CMV infections and which were known to contain CMV-specific IgM antibodies were investigated by indirect immunofluorescence for the presence of virus-specific high molecular weight IgM (19S IgM) and low molecular weight IgM (7S IgM). After sucrose gradient fractionation of the sera, 19S IgM was found in all 27 patients, whereas 7S IgM was present in 11 out of 19 (56%) patients with primary CMV infection and in 1 out of 8 (12%) patients with recurrent CMV infection. The presence of 7S IgM was unrelated to the titre of the virus-specific IgM in whole serum. The presence of IgM rheumatoid factor was monitored by a sensitive fluorescence assay using measles virus antigen/antibody complexes. The absorption of the serum fractions with heat-aggregated gamma globulin failed to remove the specific IgM staining indicating that it was not due to IgM rheumatoid factor. On the other hand adsorption with protein A/sepharose removed the specific IgM staining from the 7S IgM fractions but not from the 19S IgM fractions. This suggests that specific 19S and 7S IgM antibodies may belong to different subclasses of IgM.

IgM rheumatoid factor (RF), IgA RF, IgE RF, and IgG RF detected by ELISA in rheumatoid arthritis.

One hundred patients with rheumatoid arthritis (RA), of whom 73 were seropositive by latex or Waaler-Rose (WR) assays, or both, 100 healthy subjects, and 102 diseased controls (22 patients with systemic lupus erythematosus (SLE) and 80 with bronchial asthma) were evaluated for the presence of IgM rheumatoid factor (RF), IgA RF, IgE RF, and IgG RF by an enzyme linked immunosorbent assay (ELISA). Ninety two per cent, 65%, 68%, and 66% of the patients with RA were found to be positive for IgM, IgA, IgE, and IgG respectively. A positive correlation existed between the levels of IgM RF and IgA RF on the one hand and disease activity on the other, and the levels of IgM RF and IgA RF correlated with the levels of circulating immune complexes as measured by a C1q binding assay. The presence of extra-articular features also correlated positively with the levels of IgA RF and IgE RF. Five out of six patients with Sjögren's syndrome had very high levels of IgA RF. Of 47 patients typed for HLA-DR, DR1 and DR2 were significantly more frequent in those with the highest levels of IgM RF. Conversely, DR3 was associated with low levels or absence of IgA RF and IgE RF. These results suggest that immune response genes may regulate the level of different RF isotypes. The frequencies of IgM, IgA, IgE, and IgG RF were 59%, 36%, 9%, and 27% respectively in SLE and 25%, 2.5%, 70%, and 59% in bronchial asthma.

A study of IgM rheumatoid factors in a middle-aged population of Northern Norway

A random selection of 8807 blood samples was analysed for the presence of IgM rheumatoid factor (RF). The sera were obtained from an epidemiological survey of rheumatoid arthritis in a middle-aged population of Northern-Norway. The prevalence of IgM-RF was 1.36% for the total population, but a prevalence of IgM RF in healthy individuals between 0.48-0.49% was found with no significant difference between males and females. The majority of RF positive sera were low titred. Only 11.4% of the persons possessing serum IgM RF suffered from classical or definite rheumatoid arthritis. Eighty-one per cent of the IgM RF positive individuals converted to seronegativity in the course of 3.5 years.

IgM Rheumatoid factors in Guatemalan onchocerciasis

The possible presence of IgM Rheumatoid factors (RF) and anti-DNA antibodies was investigated in sera of patients with Guatemalan onchocerciasis. The mean value of IgM RF in the patients was found to be significantly higher than that in controls and 10 out of 57 patients had increased levels of IgM RF. In addition, serum IgM levels in those 10 patients with increased levels of IgM RF were significantly elevated. In contrast, no significant increase of serum anti-single-stranded (ssDNA) and double-stranded DNA (dsDNA) antibodies were found in the patients.

Immunoprecipitates used as a reagent for rheumatoid factors.

IgM and IgG rheumatoid factors (RFs) were purified by affinity chromatography and gel filtration. The preparations thus obtained were used as standards in a radio-immunoassay for RF detection. In this assay, RFs were reacted with immunoprecipitates, and the RFs were detected with radiolabelled (F(ab')2 fragments specific for human IgM or IgG. The reproducibility of the assay was higher when RF content was expressed relative to the standards and not directly relative to tracer binding. It was found that the presence of IgM RF did not affect the measurement of IgG RF in this RIA, since the addition of neither mono- nor polyclonal IgM RF to a donor serum resulted in increased IgG RF measurements. 100 sera were analysed and were consistently positive in only one of the tests: sheep cell agglutination or latex fixation. The 75% of the sera which were positive only in the latex fixation test were positive for IgM RF in the radio-immunoassay, indicating that RFs in this type of serum were not specific solely for human IgG.