IgG Rheumatoid Factor Research Articles

Serological and Molecular Characterization of Hepatitis C Virus-Related Cryoglobulinemic Vasculitis in Patients without Cryoprecipitate.

Prolonged B cells stimulation due to the Hepatitis C virus (HCV) can result in autoimmunity, stigmatized by rising levels of cryoglobulins (CGs), the rheumatoid factor (RF), and free light chains (FLC) of immunoglobulins (Ig) associated with a range of symptoms, from their absence to severe cryoglobulinemic vasculitis and lymphoma. Here, we aimed to identify an immunological signature for the earliest stages of vasculitis when cryoprecipitate is still not detectable. We firstly analyzed the IgG subclasses, FLC, and RF in 120 HCV-RNA-positive patients divided into four groups according to the type of cryoprecipitate and symptoms: 30 asymptomatic without cryoprecipitate (No Cryo), 30 with vasculitis symptoms but without CGs that we supposed were circulating but still not detectable (Circulating), 30 type II and 30 type III mixed cryoglobulinemia (Cryo II and Cryo III, respectively). Our results revealed that patients with supposed circulating CGs displayed a pattern of serological parameters that closely resembled Cryo II and Cryo III, with a stronger similarity to Cryo II. Accordingly, we analyzed the groups of Circulating and Cryo II for their immunoglobulin heavy chain (IgH) and T-cell receptor (TCR) gene rearrangements, finding a similar mixed distribution of monoclonal, oligoclonal, and polyclonal responses compared to a control group of ten HCV-RNA-negative patients recovered from infection, who displayed a 100% polyclonal response. Our results strengthened the hypothesis that circulating CGs are the origin of symptoms in HCV-RNA-positive patients without cryoprecipitate and demonstrated that an analysis of clonal IGH and TCR rearrangements is the best option for the early diagnosis of extrahepatic complications.

Testing for isotypes does not help differentiating rheumatoid arthritis from other rheumatoid factor positive diseases.

Rheumatoid factors (RFs) are useful for diagnosis and classification of rheumatoid arthritis (RA). Nephelometric and turbidimetric techniques, which detect total RF but do not reveal the antibody isotype, are common diagnostic methods in clinical routine. Given the recent development of isotype-specific immunoassays, the detection of IgG, IgM, and IgA RFs represents an interesting challenge. The aim of the study was to evaluate whether specific RF tests performed as a second step after traditional nephelometry could help differentiating RA from other RF-positive diseases. We tested 117 consecutive serum samples that were RF-positive at nephelometry (BNII nephelometric analyzer, Siemens) for IgA, IgG, and IgM RF isotypes by a fluoroimmunoenzymatic assay (FEIA) on the Phadia 250 instrument (ThermoFisher). Fifty-five subjects had RA and 62 presented non-RA diagnoses. Eighteen sera (15.4%) were positive only by nephelometry, two were positive only for IgA RF, and the remaining 97 sera were all positive for IgM RF isotype (with or without IgG and IgA RF). Positive findings did not correlate with RA or non-RA diagnosis. Spearman rho correlation coefficient between nephelometric total RF and IgM isotype was moderate (0.657), and weak between total RF and IgA (0.396) and IgG (0.360) isotypes. Despite its low specificity, measurement of total RF by nephelometry still seems to be the method that performs best. As IgM, IgA, and IgG RF isotypes showed only a moderate correlation with total RF measurement, their diagnostic use as a second level test remains controversial.

Lack of comparability of immunoassays for rheumatoid factor isotypes.

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterised by the presence of autoantibodies that are used for classification of the disease. Though routine diagnostics is commonly restricted to measuring rheumatoid factor (RF) and anti-citrullinated protein antibodies, detection of RF IgM, IgG and IgA isotypes, may increase the power of RA serodiagnosis by reducing the number of seronegative patients as well as provide prognostic information. The agglutination-based RF assays, such as nephelometry or turbidimetry, are unable to differentiate isotypes. We compared three different immunoassays used in current laboratory practice to detect RF isotypes. We tested 117 consecutive serum samples that were positive for total RF at nephelometry, from 55RA and 62non-RA subjects. IgA, IgG, and IgM isotypes of RF were tested by immunoenzymatic (ELISA, Technogenetics), fluoroenzymatic (FEIA, ThermoFisher) and chemiluminescence (CLIA, YHLO Biotech Co.) immunoassays. Diagnostic performance differed considerably between the assays, especially with regard to RF IgG isotype. Agreement among methods by Cohen's kappa ranged from 0.05 (RF IgG CLIA vs. FEIA) to 0.846 (RF IgM CLIA vs. FEIA). The poor agreement observed in this study indicates substantial lack of comparability among assays for RF isotypes. Harmonization of these tests requires further efforts before their measurement can be used in clinical practice.

Overlap syndrome in a 12-year-old girl with systemic lupus erythematosus and anti-oj antibody-positive polymyositis: a case report

BackgroundThe peculiar presentation of overlap syndrome in children makes precise diagnosis difficult. Children with overlap syndrome may or may not have specific antibodies. We present the case of a 12-year-old girl diagnosed with overlap syndrome of systemic lupus erythematosus (SLE) and juvenile polymyositis (JPM) who tested positive for anti-OJ antibodies.Case presentationWe describe the case of a 12-year-old girl diagnosed with SLE at the age of 7 and presented with fever with malar rash, periungual erythema, generalized weakness, and multiple joint pain at admission. The patient had persistent joint pain and weakness after intravenous methylprednisolone administration and complained of an inability to walk with a positive test for Gower's sign one week after admission, accompanied by elevated alanine aminotransferase (ALT) and creatine-phospho-kinase (CPK) levels. The results of nerve conduction velocity test were normal. Electromyography revealed abundant spontaneous activity and myopathic motor unit action potentials in the right deltoid, biceps, and iliopsoas, in addition to fibrillation and mild myopathic motor unit action potentials in the right rectus femoris muscle. Magnetic resonance imaging revealed diffusely increased signal intensities in the myofascial planes of the bilateral iliopsoas, gluteus, obturator, pectineus, and hamstring muscles. Anti-nuclear antibody, anti-RNP, and rheumatoid factor IgG tests were positive, and inflammatory myopathy autoantibodies revealed anti-OJ antibody positivity, which strongly indicated autoimmune myositis. High-resolution computed tomography of the lung revealed mild pericardial effusion without any evidence of interstitial lung disease. We initiated intravenous pulses of methylprednisolone treatment, followed by cyclosporine, mycophenolate mofetil, and oral steroids. Clinical improvement with a delayed, slowly reduced CPK level after the above treatment and she was discharged after the 18th day of hospitalization.ConclusionOverlap syndrome with inflammatory myositis can occur years later in pediatric SLE cases. We should be alert when patients with SLE develop a new presentation characterized by decreased SLE-specific autoantibody titers, positive anti-RNP antibodies, and elevated CPK. Treatment of the overlap syndrome of SLE and JPM is individualized, and the course differs between pediatric and adult patients.

P2X7 purinergic receptor plays a critical role in maintaining T-cell homeostasis and preventing lupus pathogenesis.

The severe lymphoproliferative and lupus diseases developed by MRL/lpr mice depend on interactions between the Fas lpr mutation and MRL genetic background. Thus, the Fas lpr mutation causes limited disease in C57BL/6 mice. We previously found that accumulating B220+ CD4–CD8– double negative (DN) T cells in MRL/lpr mice show defective P2X7 receptor ( P2X7)-induced cellular functions, suggesting that P2X7 contributes to T-cell homeostasis, along with Fas. Therefore, we generated a B6/lpr mouse strain (called B6/lpr-p2x7KO) carrying homozygous P2X7 knockout alleles. B6/lpr-p2x7KO mice accumulated high numbers of FasL-expressing B220+ DN T cells of CD45RBhighCD44high effector/memory CD8+ T-cell origin and developed severe lupus, characterized by leukocyte infiltration into the tissues, high levels of IgG anti-dsDNA and rheumatoid factor autoantibodies, and marked cytokine network dysregulation. B6/lpr-p2x7KO mice also exhibited a considerably reduced lifespan. P2X7 is therefore a novel regulator of T-cell homeostasis, of which cooperation with Fas is critical to prevent lymphoaccumulation and autoimmunity.

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.

IgA rheumatoid factor is associated with bone mineral density preservation in rheumatoid arthritis

Autoantibodies such as IgM rheumatoid factor (RF) and anti-citrullinated proteins/peptides antibodies (ACPA) have previously been incriminated in systemic bone loss in rheumatoid arthritis (RA). There are, however, no data describing association of IgA RF and IgG RF with systemic bone loss. This study was aimed to investigate the association of RF isotypes with systemic bone loss among patients with RA. RF isotypes and ACPA were measured by enzyme-linked immunosorbent assay among 153 patients with RA. Bone mineral density (BMD) was assessed using dual-energy X-ray absorptiometry. Ninety-four (61.4%) patients had positive IgA RF, 89 (58.2%) had positive IgG RF, 109 (71.2%) had positive IgM RF, whereas 122 (80.3%) RA patients tested positive for ACPA. Compared to the IgA RF-negative patients, IgA RF-positive patients exhibited higher disease activity and had higher RF titers. Seven (4.6%) patients had low BMD at femoral neck, 12 (7.8%) at total femur, and 47 (30.7%) at lumbar spine. IgA RF was found to be associated with protection against low BMD at spine (OR = 0.47, 95% CI = 0.23-0.95, p = 0.034). This association was further confirmed in the multivariate regression analysis taking into account several potential confounding factors(OR = 0.21, 95% CI = 0.06-0.65, p = 0.039). No association between low BMD and the presence of IgG RF or IgM RF or ACPA was found. IgA RF for the first time ever was shown to be associated with BMD preservation at spine in RA. Key points • IgA RF was associated with protection against low spinal BMD. • No association between low BMD and the presence of IgG RF or IgM RF was found.

IgA Immune Complexes Induce Osteoclast-Mediated Bone Resorption.

ObjectiveAutoantibodies are detected in most patients with rheumatoid arthritis (RA) and can be of the IgM, IgG or IgA subclass. Correlations between IgA autoantibodies and more severe disease activity have been previously reported, but the functional role of IgA autoantibodies in the pathogenesis of RA is ill understood. In this study, we explored the effect of IgA immune complexes on osteoclast mediated bone resorption.MethodsAnti-citrullinated peptide antibody (ACPA) and anti-carbamylated protein (anti-CarP) antibody levels of the IgA and IgG isotype and rheumatoid factor (RF) IgA were determined in synovial fluid (SF) of RA patients. Monocytes, neutrophils, and osteoclasts were stimulated with precipitated immune complexes from SF of RA patients or IgA- and IgG-coated beads. Activation was determined by neutrophil extracellular trap (NET) release, cytokine secretion, and bone resorption.ResultsNET formation by neutrophils was enhanced by SF immune complexes compared to immune complexes from healthy or RA serum. Monocytes stimulated with isolated SF immune complexes released IL-6 and IL-8, which correlated with the levels of ACPA IgA levels in SF. Osteoclasts cultured in the presence of supernatant of IgA-activated monocytes resorbed significantly more bone compared to osteoclasts that were cultured in supernatant of IgG-activated monocytes (p=0.0233). Osteoclasts expressed the Fc receptor for IgA (FcαRI; CD89) and Fc gamma receptors. IgA-activated osteoclasts however produced significantly increased levels of IL-6 (p<0.0001) and IL-8 (p=0.0007) compared to IgG-activated osteoclasts. Both IL-6 (p=0.03) and IL-8 (p=0.0054) significantly enhanced bone resorption by osteoclasts.ConclusionIgA autoantibodies induce release of IL-6 and IL-8 by immune cells as well as osteoclasts, which enhances bone resorption by osteoclasts. We anticipate that this will result in more severe disease activity in RA patients. Targeting IgA-FcαRI interactions therefore represents a promising novel therapeutic strategy for RA patients with IgA autoantibodies.

Comparative Analyses of Serological Biomarkers and Disease Characteristics between Elderly-onset and Younger-onset Rheumatoid Arthritis

The onset of rheumatoid arthritis (RA) may occur any time after the age of 16 years. The purpose of this study was to compare the clinical and serological differences between elderly onset RA (EORA); which is begins at the age of 60 and above, with younger onset RA (YORA). A total of 69 EORA and 82 YORA female patients were enrolled in this study. Data on medications, disease duration, age at onset, disease activity at onset and laboratory parameters were collected by reviewing the medical records. All patients had their blood samples taken for serum anticyclic citrulinated peptide (anti-CCP), IgA rheumatoid factor (RF), IgM RF and IgG RF. Besides, the subjects were assessed for their radiographic joint damage based on Modified Sharp Score (MSS) and functional disability based on the Health Assessment Questionnaire-disability Index (HAQ-DI) scores. Despite comparable disease duration and frequency of seropositivity, the YORA group had significantly higher disease activity at onset of the disease (p=0.009). In keeping with this finding, the YORA group had more severe joint damage based on radiographic assessment (MSS scores of 17.49+19.04 versus 10.04+12.79). The YORA group had significantly higher levels of IgA RF and anti-CCP with p-values of 0.035 and 0.002, respectively. Our findings suggest that YORA is associated with more severe disease, worse radiographic joint damage and higher levels of anti-CCP and IgA RF.

AB0155 COMPARATIVE ANALYSES OF SEROLOGICAL BIOMARKERS AND DISEASE CHARACTERISTICS BETWEEN ELDERLY ONSET RHEUMATOID ARTHRITIS (EORA) AND YOUNGER ONSET RHEUMATOID ARTHRITIS (YORA)

Background:Several studies have reported differences in disease characteristics between elderly onset RA (EORA: age of onset &gt; 60 years) and younger-onset RA (YORA). However, the findings across the studies have been rather inconsistent owing partially to the genetic variation across the populations studied. While a few studies have looked into the clinical aspects of EORA, there is a profound lack of comparative data on serological findings between EORA and YORA. Seropositive RA is known to be associated with more aggressive disease and the titres of the autoantibodies may predict the disease activity and the severity of radiographic progression.Objectives:The main aim of this study was to compare the levels of the autoantibodies namely anti–CCP (cyclic citrulinated peptide), IgA, IgM, IgG rheumatoid factors(RF) and disease characteristics between the EORA and YORA groups.Methods:We consecutively recruited a total of 151 female RA patients who were tested for IgA RF, IgG RF, IgM RF and anti CCP antibodies. Participants were aged above 18 years and met the 2010 ACR/EULAR RA criteria. Data on the disease characteristics (age at onset, disease activity at onset, disease duration and medications)were obtained by reviewing the medical records of the subjects. Subjects were divided into 2 groups i.e EORA and YORA based on age at onset of RA. All subjects were assessed for the severity of radiographic joint damage and functional disability based on Modified Sharp Score (MSS) and Health-assessment questionnaire-disability index (HAQ- DI), respectively. The EULAR response criteria was used to determine the subjects’ response to disease-modifying anti-rheumatic drugs.Results:The EORA group had 69 patients whereas the YORA group had 82 patients. The mean anti-CCP and IgA RF levels were significantly higher in the YORA group with p values of 0.002 and 0.035, respectively. The YORA group had significantly more severe disease at onset (p value for DAS 28 at onset was 0.009) with worse radiographic joint damage (p value for MSS was 0.006). In parallel with these findings, the YORA group had significantly higher ESR and CRP at onset with higher frequency of subjects requiring advanced therapies. The differences in frequency of RF positivity, disease duration, number of DMARDs, prednisolone dose and HAQ-Di scores between the groups did not reach statistical significance.Conclusion:EORA is characterized by lower levels of anti-CCP and IgA autoantibodies with less aggressive disease as compared to YORA.

POS0482 WOOD SMOKE EXPOSURE IS ASSOCIATED WITH HIGHER ANTI-CCP ANTIBODY TITERS IN HISPANIC PATIENTS WITH RHEUMATOID ARTHRITIS

Background:Wood smoke exposure is a risk factor for the development of chronic obstructive pulmonary disease (COPD), lung cancer and cardiovascular disease and it has also been linked to higher anti-CCP antibodies in patients with rheumatoid arthritis (RA) and COPD (1).Objectives:The objective of the present study is to report the correlation between anti-CCP, IgG, IgM and IgA rheumatoid factor (RF) to wood smoke exposure in patients with RA. Additionally, evaluate the impact of disease activity, biomass exposure, and disease duration on anti-CCP antibody levels.Methods:A cross-sectional, observational study was designed based on a cohort of Hispanic RA patients. All fulfilled the 2010 ACR/EULAR classification criteria for RA. Biomass smoke exposure was expressed using the biomass exposure index (BEI) calculated from the mean of exposed hours per day multiplied by the number of years exposed. Subjects were divided into two groups: those exposed to wood smoke with BEI ≥1 and subjects not exposed to wood smoke. They were matched by age, gender, and comorbidities. Anti-CCP antibodies and RF were measured by ELISA with cutoff points of &lt;5 U/mL and &lt;20 U/mL respectively.Results:A total of 318 subjects were included, 159 (50%) of them had a history of exposure to wood smoke. Anti-CCP antibody positivity was present in 102 (64.2%) with a median titer of 97.1 U/mL (1.7-198) in the RA exposed group, and in 89 (56%) with a median titer of 8.5 U/mL (1.1-145) in the RA non-exposed group. A significant difference was found in anti-CCP antibody titers between groups (p=0.003). (Table 1). Spearman’s rho showed a small but statistically significant correlation between BEI and anti-CCP antibody titers (rho= 0.170, p=0.002). Biomass exposure was independently related to higher anti-CCP antibody titers (B=35.4, p&lt;0.001).Conclusion:RA patients who were exposed to wood smoke had higher titers of anti-CCP antibodies than non-exposed RA patients. Furthermore, biomass exposure was shown to be independently related to higher titers of anti-CCP antibodies.

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.

Serological and hematological characteristics of Sjogren’s syndrome and dry eye syndrome patients using a novel immune serology technique

ObjectivesTo compare hematologic and serological parameters among patients with Sjogren’s syndrome (SS), dry eye syndrome (DES) and controls, and validate a novel multiplex-serology method for identifying auto-antibodies in these populations.MethodsIn a clinic-based case-control study a total of 422 participants were recruited, including 91 with SS, 120 DES, and 211 controls (age and sex frequency-matched). We measured blood counts, anti-nuclear-antibodies (ANA), anti-SSA/SSB, anti-ribonucleoprotein (RNP), anti-double-stranded-DNA (DS-DNA), and rheumatoid factor (RF) using the “Immunodot” qualitative-ELISA assay. Immunoglobulins, C3 and C4 were measured by immune-fluorescence. Autoantibodies were also quantified with a newly-developed method using glutathione-S-transferase fusion proteins of SSA/Ro 52 and 60kD and SSB/La (multiplex-serology), measuring median fluorescence intensity (MFI).ResultsAmong DES patients, only 2% (95%CI: 0.36–6.3) had positive immune serology. SS patients had lower lymphocyte, hemoglobin and C3 levels but higher prevalence of RF, ANA, anti-SSA/B and higher IgG and MFI levels, compared to DES and controls (P<0.001). Presence of anti-SSA/Ro-52kD was associated with SS [odds ratio (OR) = 2.05, 95% confidence interval (CI): 1.46–2.88]. Anti-SSB/La was inversely associated with DES (OR = 0.81, 95%CI: 0.65–1.00) compared to controls. Positivity to RF (adjusted for age, gender and ethnicity OR = 5.03, 95%CI: 1.78–14.21), ANA (OR = 14.75, 95%CI: 4.09–53.17), or combination of anti-SSA/B (OR = 20.97, 95%CI: 4.60–95.54) were more likely in SS compared to DES. The novel multiplex-serology method correctly identified anti-SSA/B autoantibodies by ELISA among SS, DES patients and controls (sensitivity = 1.0, negative-predictive-value = 1.0).ConclusionsSerologic parameters distinguish SS from DES patients and controls. A newly-developed multiplex-serology technique may be useful to detect autoantibodies in large epidemiologic studies.

Levels of Anti-Citrullinated Protein Antibodies and Rheumatoid Factor, Including IgA Isotypes, and Articular Manifestations in Ulcerative Colitis and Crohn's Disease.

Systemic presence of arthritis autoantibodies (AAb) is specific for rheumatoid arthritis (RA). AAb initiation might be triggered by chronic mucosal inflammation, such as in inflammatory bowel disease (IBD). We assessed the prevalence of anti-citrullinated protein antibodies (ACPA) and rheumatoid factor (RF) in ulcerative colitis (UC) and Crohn’s disease (CD) patients, with regard to the prevalence of joint complaints in AAb+ versus AAb− IBD patients. RA patients and healthy subjects (HC) served as controls. Serum was collected from 226 UC, 165 CD and 86 RA patients, and 36 HCs. One-hundred-and-ten UC (48.7%) and 76 CD (46.1%) patients were seropositive for at least one autoantibody, compared to 4 (13.9%) HCs and 81 (94.2%) RA patients. Eighty-three (37%) UC and 52 (32%) CD patients were seropositive for the anti-cyclic citrullinated protein antibody (anti-CCP2) of the immunoglobulin A type (IgA anti-CCP2), compared to 1 (2.8%) HC and 64 (74%) RA patients. RF of the immunoglobulin G type (IgG RF) and IgA RF seropositivity in UC and CD patients was comparable to HCs and low compared to RA patients. Arthralgia was reported by 34 (18.7%) UC and 50 (33.1%) CD patients, but presence of arthralgia was not increased in AAb+ patients. AAbs are frequently present in IBD patients, supporting the hypothesis that inflammation of intestinal mucosa induces low systemic levels of ACPA.

High frequency of rheumatic regional pain syndromes in first-degree relatives of patients with rheumatoid arthritis.

First-degree relatives (FDR) of patients with rheumatoid arthritis (RA) have a higher risk for the development of RA. In the stages prior to the development of arthritis, nonspecific musculoskeletal (MSK) manifestations may occur. The aim of the study is to describe the frequency of rheumatic regional pain syndromes (RRPS) in FDR of RA patients. A cross-sectional study was carried out from July 2016 to September 2018. Parents, offspring, and siblings of RA patients completed the Community Oriented Program in the Rheumatic Diseases (COPCORD) questionnaire. Rheumatoid factor (RF) IgG, IgM, and IgA; anticitrullinated peptide antibodies (ACPAs); C-reactive protein (CRP); and erythrocyte sedimentation rate (ESR) were determined. All subjects with a positive COPCORD (defined by the presence of musculoskeletal pain) were evaluated and classified. Three hundred thirty-five FDRs participated, 75.8% were female, mean age of 44.15years; 138 (41.2%) were diagnosed with at least one RRPS; 72 (21.5%) had rotator cuff tendinitis, 51 (15.2%) pes anserine bursitis, and 39 (11.6) lateral epicondylitis; RA was diagnosed in 24 (7.16%) subjects, undifferentiated arthritis (UA) in 30 (8.9%) and inflammatory arthralgia (AI) in 104 (31%). We found anti-CCP positivity in 6.8%, RF IgA in 22.3%, RF IgM in 48.6%, and RF IgG in 8.9%. The presence of RRPS was higher in this RA-FDR group compared to general population. Clinical evaluation of this risk group should include screening for RRPS.

Endothelial damage and circadian blood pressure profile in rheumatoid arthritis

To study the influence of the state of endothelium on the daily profile of arterial pressure (AP) in patients with rheumatoid arthritis (RA). In 70 RA pts carried out C-reactive protein (CRP), vascular endothelial adhesion molecule type 1 (sVCAM-1), antigen von Willebrand Factor (AG WF), interleukin-8 (Il-8), rheumatoid factor (RF), IgG, endotheline-1 (ET-1), number of desquamated endotheliocytes cells (DE), VS, activity of renin by immunoenzyme analysis. The dysfunction of endothelium was evaluated by calculation of DE. The functional methods included the daily monitoring of arterial pressure (AP). Arterial hypertension (AH) occurred in 40 (57.1%) pts. RA pts are revealed the signs of endothelial dysfunction, about which significant differences among the indices of activation of endothelium in comparison with control group testify. ET-1, sVCAM-1, vWF AG, Il-8, CRP content was higher in RA pts. Reliably above there was a number of DE. Reliable differences according to these indices depending of RA activity were discovered. With conducting of correlation analysis it is revealed, that markers of the activation of endothelium: sVCAM-1, vWF AG positively correlated with increasing RF IgG and indices of the immune inflammation: CRP, and DE number. In patients suffering from RA, showed signs of endothelial dysfunction. The positive correlation between endothelial damage and daily profile of AP show the relationship of these processes. Positive correlations between the damage of endothelium and disturbance of AP daily profile testify about the interrelation of these processes.

Fra1 Controls Rheumatoid Factor Autoantibody Production by Bone Marrow Plasma Cells and the Development of Autoimmune Bone Loss.

Next to proinflammatory cytokines, autoimmunity has been identified as a key trigger for osteoclast activation and bone loss. IgG-rheumatoid factor (IgG-RF) immune complexes, which are present in patients with rheumatoid arthritis, were shown to boost osteoclast differentiation. To date, the regulation of IgG-RF production in the absence of inflammatory triggers is unknown. Herein, we describe Fra1 as a key checkpoint that controls IgG-RF production by plasma cells and regulates autoimmune-mediated bone loss. Fra1 deficiency in B cells (Fra1ΔBcell ) led to increased IgG1-producing bone marrow plasma cells, enhanced IgG-RF production, and increased bone loss associated with elevated osteoclast numbers after immunization. The effect of IgG-RF on osteoclasts in vitro and on osteoclasts associated with bone loss in vivo was dependent on FcγR, especially FcγR3. Furthermore, immunization of WT mice with T-cell-dependent antigens induced a significant and robust decrease in Fra1 expression in bone marrow B cells, which was followed by increased IgG1 production and the induction of osteoclast-mediated bone loss. Overall, these data identify Fra1 as a key mediator of IgG-RF production and autoimmune-mediated bone loss. © 2019 American Society for Bone and Mineral Research.

Occurrence of anti-CCP2 and RF isotypes and their relation to age and disease severity among Sudanese patients with rheumatoid arthritis

ObjectiveAnti-cyclic citrullinated peptide 2 antibodies (anti-CCP2) and rheumatoid factor (RF) in rheumatoid arthritis (RA) has been extensively assessed in industrialized countries. We investigated the diagnostic and prognostic impact of anti-CCP2 and RF isotypes in a Sudanese cross-sectional RA cohort.MethodsConsecutive RA patients (n = 281) diagnosed according to the 1987 ACR criteria were included 2008–2010. Anti-CCP2 and RF isotypes (IgA, IgM, and IgG) were measured by enzyme immunoassay in 262 patients, with reference intervals aligned to the same diagnostic specificity as for anti-CCP2 (97.6%) using national controls.ResultsIgA RF was the predominant RA-associated autoantibody (56%), followed by IgM RF and anti-CCP2 (both 52%) and IgG RF (49%). In receiver operator characteristic analysis, IgA RF also showed the largest area under the curve. Patients with IgG RF were younger and had 8 years lower median age of disease onset compared to antibody negative patients (p < 0.0001). IgG RF was the only marker associated with a high number of involved joints (p = 0.028), and together with anti-CCP2 were the strongest markers for finger deformities (p = 0.016 and p = 0.012), respectively. No statistical differences were found for disease duration, ESR and Hb levels, and occurrence of erosions/osteopenia for any of the investigated autoantibodies.ConclusionWhereas IgA RF showed the best diagnostic performance, IgG RF associated with low age of RA onset, high number of involved joints, and finger deformities. These findings indicate that RA-associated antibodies other than conventional IgM RF and anti-CCP2 might be informative in non-Caucasian RA populations.

Comparison of rheumatoid factor of IgM, IgG and IgA isotypes with disease activity score 28 in patients of rheumatoid arthritis

Introduction/background: Rheumatoid factor (RF) is a widely used serological marker for the diagnosis of rheumatoid arthriris (RA). RF can be detected in up to 70 to 80% of RA patients and it is associated with disease activity, bone erosion, and disease outcome. RF is an autoantibody targeting the 'fraction crystallizable' (Fc) region of IgG antibodies and exists as IgA, IgG and IgM isotypes. The objective of this study was to compare the RF isotypes IgM, IgG and IgA with disease activity score 28 in rheumatoid arthritis patients. Materials and Methods: This was a descriptive study, which included 83 RA patients. Blood samples of the patients were collected from the Department of Rheumatology, Sheikh Zayed Hospital Lahore. The levels of different isotypes of RF i.e. IgM, IgG and IgA were determined by ELISA technique. Data was analysed by SPSS 20.0. Results: RF, IgM, IgG, and IgA isotype, was detected in 83%, 10%, and 40% of RA patients respectively. RF istoypes were compared with DAS28. There was no significant association between DAS 28 and RF IgM [Odd ratio (CI)] [0.5(0.07-3.18)], RF IgG [3.0(0.27-32.20)] and RF IgA [0.4(0.43-0.13)]. Disease duration was also compared with RF isotypes but no significant association found. There was no significant association between disease duration and RF IgM [Odd ratio (CI)] [1.4(0.46-4.86)], RF IgG [1.6(0.50-5.0)] and RF IgA [1.1(0.53-2.7)]. Conclusion: All the isotypes of RF were detected in RA patients. As a screening method for rheumatoid arthritis the IgM-RF is superior to other RF isotypes. RF titer may be valueable in estimation of disease activity and other inflammatory parameters in RA patients.

Rheumatoid factor isotype and Ro epitope distribution in primary Sjögren syndrome and rheumatoid arthritis with keratoconjunctivitis sicca.

Primary Sjögren syndrome (pS) is associated with autoantibodies such as rheumatoid factor (RF) and anti-nuclear antibodies such as anti-Ro (SS-A) and/or La (SS-B). Recent developments within autoimmune diagnostics allow quantitation of RF subclasses and anti-Ro epitopes. Will this refinement by autoimmune diagnostics help predicting development of extraglandular manifestations (EGM) in pS patients? A cohort of pS and rheumatoid arthritis (RA) patients with keratoconjunctivitis sicca (n = 35 and 16, resp) was included. Of the pS patients, 54% developed one or more EGM. Antibodies quantitated were IgM-RF, IgA-RF, IgG-RF, anti-Ro52, and anti-Ro60. Upon analysis of RF isotypes, pS patients generally displayed higher IgA-RF concentrations than RA patients (126 versus 49U/ml, p = 0.015), while the dominant RF isotype in RA patients was IgM-RF (82.5 versus 38U/ml, p = 0.012). No differences were observed regarding IgG-RF concentrations. In pS without/with EGM, the median RF IgM concentrations were similar, while RF IgA and IgG concentrations tended to be lower in pS patients with EGM > 1. Both Ro epitopes were strongly recognized by almost all pS patients, independent from EGM, while these antibodies were absent in RA patients. Primary Sjögren syndrome and RA patients have distinct serological profiles when analysing RF and Ro-specific antibodies. A longitudinal study of switched RF isotypes in pS patients is worthwhile from an immunological point of view, but its value is limited regarding identification of pS patients prone to developing EGM or RA patients prone to developing secondary sicca symptoms.