IgA Rheumatoid Factor Research Articles

A rheumatoid factor paradox: inhibition of rituximab effector function

IntroductionRituximab (RTX) therapy of rheumatoid arthritis (RA) exhibits enhanced effectiveness in seropositive patients. Using patient sera, we tested if this improved efficacy was associated with enhanced RTX mediated complement-dependent cytotoxicity (RTX-CDC).MethodsWe developed an in vitro assay for RTX-CDC using patient sera and the Daudi human B cell line. Using propidium iodide uptake and flow cytometry, we compared RTX-CDC with rheumatoid factor (RF)+ sera relative to normal volunteer, non-RA and RF- sera. Additional studies examined mixing studies of RF+ and RF- sera, as well as the effect of monoclonal IgA or IgM RF. Finally, the effect of RF on RTX mediated trogocytosis of normal B cells was evaluated.ResultsUsing human sera, addition of RTX resulted in rapid and profound (> 50%) Daudi cell death that was complement dependent. Surprisingly, RF+ patient sera exhibited reduced RTX-CDC relative to RF- sera, with an inverse relationship of RTX-CDC and RF titer. Mixing studies indicated the presence of an inhibitor of RTX-CDC in RF+ sera. The addition of monoclonal IgM or IgA RF to RF- sera markedly inhibited RTX-CDC. This effect was specific for RF binding to the Fc portion of RTX as it was not apparent with the F(ab)' domains of RTX engineered onto IgG3 heavy chain. RF also modestly inhibited RTX mediated trogocytosis.ConclusionsContrary to expectations, RF+ sera exhibits reduced RTX-CDC due to the presence of RF. The enhanced efficacy of RTX in seropositive RA patients cannot be attributed to improved B cell depletion through CDC. This result indicates that high RF levels may potentially modulate the efficacy of any therapeutic monoclonal antibody dependent on Fc effector function.

DIAGNOSTIC VALUE OF SEROLOGICAL MARKERS OF RHEUMATOID ARTHRITIS

Rheumatoid arthritis (RA) is a classic autoimmune disease associated with the production of wide range of autoantibodies, and their detection has diagnostic and prognostic implication. The objective of this study was to estimate the diagnostic value of antibodies against modified citrullinated vimentin (AMCV) and nuclear antigen RA33 of the IgA rheumatoid factor (RF) versus the value of routinely used profile of autoantibodies in diagnostic work-up of RA. Material and methods. 253 patients with RA prehistory of varying duration were included into the study group. The control group was comprised of 92 patients, including patients with seronegative spondyloarthropathies and diffuse connective tissue diseases, as well as sex and age matched healthy controls. Serum levels of IgM and IgA RF, antibodies against cyclic citrullinated peptide (ACCP), ACMV, anti-keratin antibodies (AKA), antibodies against RA33 antigen (ARA33) and antinuclear factor (ANF) were measured in all patients and controls. Results and discussion. Diagnostic sensitivity of AMCV equaled 78%, ACCP — 77%, IgM RF — 71%, IgA RF — 43%, AKA — 43%, ARA33 — 31% and ANF — 31%. All anti-citrullinic antibodies (AKA, ACCP, ACMV) were significantly more commonly associated with IgM RF. Among RF and ACCP seronegative patients ACMV were found in 24% cases with 20 IU/Ml detection threshold, and in 21% — with 30 IU/Ml, allowing to increase diagnostic specificity of the test up to 91% with the increment of diagnostic threshold. Incidence of ARA33 was not significantly different among the RF and ACCP positive or negative subgroups, thus making ARA33 an independent RA marker. Specificity of this marker was 87,9%, thus making it inferior to RF and ACCP by a composite of diagnostic characteristics. Conclusions. Integrated measurement of ACMV and ARA33 is a rational approach at the second stage of serologic testing work-up in suspected cases of RA onset, when initial RF and ACCP tests were negative.

Multiple cytokines and chemokines are associated with rheumatoid arthritis-related autoimmunity in first-degree relatives without rheumatoid arthritis: Studies of the Aetiology of Rheumatoid Arthritis (SERA)

ObjectiveWe investigated whether rheumatoid arthritis (RA)-related autoantibodies were associated with systemic inflammation in a prospective cohort of first-degree relatives (FDRs) of RA probands, a population without RA but at increased...

Evidence of fibrinogen as a target of citrullination in IgM rheumatoid factor-positive polyarticular juvenile idiopathic arthritis

Several studies have noted the significance of measuring anti-cyclic citrullinated peptide (CCP) antibodies in juvenile idiopathic arthritis (JIA) as an important indicator for destructive disease, as is the case in rheumatoid arthritis (RA). While the role of anti-CCP antibodies in RA and JIA has become better understood, the identity of the target proteins of this modification has remained elusive. In this study, we evaluated serum from patients with various subtypes of JIA to investigate the presence of anti-deiminated (citrullinated) fibrinogen and anti-citrullinated α-enolase antibodies, and their association with RF and anti-CCP antibody isotypes.Sera were obtained from 96 JIA patients, 19 systemic lupus erythematosus (SLE) patients, and 10 healthy children. All sera were measured for antibodies against citrullinated and native fibrinogen and α-enolase by an enzyme linked immunosorbent assay (ELISA). In addition, all sera were assayed for anti-CCP antibody isotypes and rheumatoid factor (RF) isotypes by ELISA. The relationship between anti-citrullinated fibrinogen and anti-α-enolase antibodies and disease activity and joint damage were also investigated. All results were correlated with clinical and laboratory parameters using Spearman's rho correlation coefficient. Multiple logistic regression analysis was utilized to identify which variables were associated with joint erosions and diagnosis of JIA.Thirty-one JIA patients (32%) demonstrated reactivity to citrullinated fibrinogen and 9 (9%) to citrullinated α-enolase. Reactivity to citrullinated fibrinogen and α-enolase was predominantly found in IgM RF-positive polyarthritis patients. Fourteen JIA patients reacted with native α-enolase and a higher percentage of SLE patients reacted with citrullinated α-enolase when compared to JIA patients. Anti-citrullinated fibrinogen antibodies correlated with the presence of IgG anti-CCP antibodies and IgA and IgM RF. The presence of anti-citrullinated α-enolase antibodies correlated with IgA anti-CCP antibodies. IgG anti-CCP antibodies were significantly associated with joint damage and anti-citrullinated fibrinogen antibodies were strongly associated with JIA when compared to control groups. Anti-citrullinated fibrinogen antibodies demonstrated high sensitivity (81%) for IgM RF-positive polyarticular JIA. IgG anti-CCP antibodies had the highest specificity (95%) for JIA, with anti-citrullinated fibrinogen antibodies, IgA anti-CCP antibodies and IgA RF all following at 84%.JIA patient sera exhibited strong reactivity to anti-citrullinated fibrinogen antibodies and demonstrated high sensitivity and specificity for JIA, primarily in IgM RF-positive polyarthritis patients. Fibrinogen is one of several protein targets for citrullination in JIA.

Impact of tocilizumab therapy on immunological parameters in patients with rheumatoid arthritis

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Induction of IgA Deposits and Glomerulonephritis by IgA Rheumatoid Factor

Induction of IgA Deposits and Glomerulonephritis by IgA Rheumatoid Factor

O-Glycosylated IgA Rheumatoid Factor Induces IgA Deposits and Glomerulonephritis

Structural aberrations of O-linked glycans present in the IgA1 hinge region are associated with IgA nephropathy, but their contribution to its pathogenesis remains incompletely understood. In this study, mice implanted with hybridoma secreting 6-19 IgA anti-IgG2a rheumatoid factor, but not 46-42 IgA rheumatoid factor bearing the same IgA allotype, developed mesangial deposits consisting of IgA, IgG2a, and C3. Studies in immunoglobulin- and C3-deficient mice revealed that the development of these glomerular lesions required the formation of IgA-IgG2a immune complexes and subsequent activation of complement. The proportion of polymeric and monomeric forms, the IgG2a-binding affinity, and the serum levels of IgA-IgG2a immune complexes were similar between 6-19 IgA- and 46-42 IgA-injected mice. In contrast, the analysis of oligosaccharide structures revealed highly galactosylated O-linked glycans in the hinge region of 6-19 IgA and poorly O-glycosylated in the hinge region of 46-42 IgA. Furthermore, the structure of N-linked glycans in the CH1 domain was the complex type in 6-19 IgA and the hybrid type in 46-42 IgA. In summary, this study demonstrates the presence of O-linked glycans in the hinge region of mouse IgA and suggests that 6-19 IgA rheumatoid factor-induced GN could serve as an experimental model for IgA nephropathy.

Autoanticorpos na artrite reumatoide inicial: coorte Brasília - resultados de uma análise seriada de três anos

The diagnostic and prognostic value of the serial measurement of antibodies, such as rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP), and anti-citrullinated vimentin (anti-Sa) antibodies, has not been defined in early rheumatoid arthritis (ERA). To prospectively assess the presence of RF, anti-CCP, and anti-Sa in ERA patients. Forty ERA (less than 12 months) patients of the Brasília cohort were evaluated and followed up for three years. Both clinical and demographic data were recorded, in addition to the results (ELISA) of RF (IgM, IgG, and IgA), anti-CCP (CCP2, CCP3, and CCP3.1), and anti-Sa at the baseline assessment and after 3, 6, 12, 18, 24 and 36 months of follow-up. The results were compared by use of Student t test and paired t test. The patients' mean age was 45 years, and 90% of them were female. At the time of diagnosis, RF was identified in 50% of the patients (RF IgA, 42%; RF IgG, 30%; and RF IgM, 50%), anti-CCP in 52.5% (no difference between CCP2, CCP3, and CCP3.1), and anti-Sa in 10%. After three years, no difference was observed in RF and anti-CCP prevalence, but anti-Sa increased to 17.5% (P = 0.001). Repeated RF and anti-CCP measurement, including different isotypes, during three years of follow-up showed no significant changes. The third generation of anti-CCP assays did not increase the diagnostic value of the second-generation assays.

Antibodies against cyclic citrullinated peptides of IgG, IgA and IgM isotype and rheumatoid factor of IgM and IgA isotype are increased in unaffected members of multicase rheumatoid arthritis families from northern Sweden

BackgroundRheumatoid factors (RFs) and antibodies against cyclic citrullinated peptides (CCPs) of IgG, IgA and IgM isotype have been shown to precede disease onset by years.ObjectiveTo evaluate serological risk markers in...

Rheumatoid factor isotypes in patients with erosive osteoarthritis of the hand

Dear Editor, Erosive osteoarthritis (EOA) is generally considered an uncommon subset of osteoarthritis (OA), targeting interphalangeal (IP) joints and characterized by an abrupt onset, marked pain, functional impairment, inflammatory symptoms and signs, including stiffness, soft tissue swelling, erythema, paraesthesiae and a worse clinical outcome than non-erosive OA of the hand (HOA).1 Laboratory tests are usually negative, despite clinical findings of inflammation, even though a slight increase of erythrocyte sedimentation rate (ESR) and high sensitive C-reactive protein (hsCRP), although at low degree, are noticeable.2 Furthermore, in a previous study, we showed the absence of anti-cyclic citrullinated peptide antibodies (anti-CCP), in blood samples of a group of EOA patients.3 Erosive osteoarthritis is defined radiographically by subchondral erosion, cortical destruction and subsequent reparative change, which may include bony ankylosis.1,4 Moreover, in the early stages of this disease, the differential diagnosis between EOA and other arthritis types, such as rheumatoid arthritis (RA) or psoriatic arthritis (PsA), may pose a challenge.5,6 Rheumatoid factor (RF) is a family of autoantibodies that recognizes the Fc part of IgG molecules and exists as IgA, IgG and IgM isotypes.7 The present study is aimed at detecting for the first time the prevalence of sera IgA, IgG and IgM RF in patients affected by EOA, compared to patients with nodal osteoarthritis (NOA), RA and healthy subjects. HOA diagnosis was made according to the American College of Rheumatology (ACR) criteria for HOA.8 EOA and NOA were defined by European League Against Rheumatism (EULAR) recommendations.1 RA is defined by the ACR criteria.9 Thirty-two consecutive patients with EOA (five men and 27 women, median age 59.2 years, range 49–75), attending the outpatient Rheumatology Unit of Siena Hospital, were enrolled in the study. Each patient showed the common EOA radiographic findings.1,4 The control group included 30 patients affected by NOA,1 32 RA patients and 30 healthy subjects, sex- and age-matched. For all the studied subjects, co-morbidities such as infections, cancer, renal and liver diseases, cryoglobulinemia, scleroderma, Sjogren syndrome, autoimmune thyroiditis, PsA, undifferentiated spondyloarthropathies, gout and pseudogout, were excluded. After informed consent was obtained, serum samples were stored at −20°C until tested to anti-CCP antibodies and IgA, IgG and IgM RF. Anti-CCP antibodies were tested by FEIA technique, by using EliA system (Phadia Diagnostics, Freiburg, Germany); IgA, IgG and IgM RF were assessed using enzyme-linked immunosorbent assay (ELISA) commercial kits (Orgentec Diagnostica, Mainz, Germany). We considered positive every IgA, IgG and IgM RF > 20 U/mL. All EOA patients, NOA patients and healthy controls were negative for anti-CCP, IgA-RF, IgG-RF and IgM-RF. In the RA group, 77% of the patients were found to be positive for anti-CCP, 35% for IgM and IgG RF and 52% for IgA RF. Although a relationship between EOA and RA was first suggested by Ehrlich,10 there have been few studies concerning the serological tests for RF in EOA. In our study the detection and quantitative measurement of RF in various immunoglobulin classes (IgA, IgG and IgM) was performed using ELISA, for its specificity and sensitivity. Using this technique, in the literature we found that the majority (up to 70–80%) of RA patients presented an increase of two or three RF isotypes.11 Our study suggests that the combined detection of the three isotypes of RF and of anti-CCP antibodies may be helpful in the differential diagnosis between EOA and RA, especially in equivocal cases. The absence of the three isotypes of RF and of anti-CCP antibodies in the serum of the EOA patients shows that EOA represents a subtype of HOA and not a specific inflammatory disease.

Atacicept in patients with rheumatoid arthritis and an inadequate response to methotrexate: Results of a phase II, randomized, placebo-controlled trial

To assess the efficacy, safety, and biologic activity of atacicept in tumor necrosis factor antagonist-naive patients with rheumatoid arthritis (RA) in whom the response to methotrexate treatment was inadequate. In this phase II study, patients with active RA (n = 311) were randomized 1:1:1:1 to receive placebo, atacicept 150 mg weekly with or without a 4-week loading period (twice-weekly dosing), or open-label adalimumab 40 mg every other week, for 25 weeks. The primary end point was 20% improvement in disease severity according to the American College of Rheumatology criteria, assessed using the C-reactive protein level (ACR20-CRP), at week 26. Secondary end points included additional assessments of efficacy, biologic activity, and safety. The proportion of patients meeting the primary end point (ACR20-CRP response) did not differ significantly in the atacicept groups and the placebo group (46% in the placebo group, 45% in the atacicept loading group, and 58% in the atacicept nonloading group). In contrast, an ACR20-CRP response was observed in 71% of patients in the adalimumab group (P < 0.001 versus placebo). ACR50-CRP response rates were significantly higher in all active-treatment groups compared with placebo, but ACR70-CRP response rates were superior only in the adalimumab group. Atacicept treatment reduced the levels of serum IgG, IgA, and IgM rheumatoid factor and the levels of circulating mature B cells and plasma cells. The effects of treatment were similar with and without loading. Immunoglobulin levels returned toward baseline values during the treatment-free followup period (week 38). The most frequent adverse events associated with atacicept represented common illnesses. No serious infections occurred among patients treated with atacicept. The primary end point (ACR20-CRP response) was not met despite significant biologic effects of atacicept that were consistent with its proposed mechanism of action. Modest effects of atacicept were seen for some secondary efficacy end points. Treatment with atacicept raised no new safety concerns.

TIME COURSE OF CHANGES IN LABORATORY BIOMARKERS IN PATIENTS WITH RHEUMATOID ARTHRITIS DURING TOCILIZUMAB THERAPY

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Clinical Images: Bone sarcoidosis mimicking multiple metastases

vascularity. Am J Reprod Immunol 2004;51:257–68. 45. Wong M, Toh L, Wilson A, Rowley K, Karschimkus C, Prior D, et al. Reduced arterial elasticity in rheumatoid arthritis and the relationship to vascular disease risk factors and inflammation. Arthritis Rheum 2003;48:81–9. 46. Cooper GS. Unraveling the etiology of systemic autoimmune diseases: peering into the preclinical phase of disease. J Rheumatol 2009;36:1853–5. 47. Leslie D, Lipsky P, Notkins AL. Autoantibodies as predictors of disease. J Clin Invest 2001;108:1417–22. 48. Majka DS, Holers VM. Can we accurately predict the development of rheumatoid arthritis in the preclinical phase? [editorial]. Arthritis Rheum 2003;48:2701–5. 49. Rantapaa-Dahlqvist S, de Jong BA, Berglin E, Hallmans G, Wadell G, Stenlund H, et al. Antibodies against cyclic citrullinated peptide and IgA rheumatoid factor predict the development of rheumatoid arthritis. Arthritis Rheum 2003;48:2741–9.

Evidence of fibrinogen as a target of citrullination in IgM rheumatoid factor-positive polyarticular juvenile idiopathic arthritis.

BackgroundSeveral studies have noted the significance of measuring anti-cyclic citrullinated peptide (CCP) antibodies in juvenile idiopathic arthritis (JIA) as an important indicator for destructive disease, as is the case in rheumatoid arthritis (RA). While the role of anti-CCP antibodies in RA and JIA has become better understood, the identity of the target proteins of this modification has remained elusive. In this study, we evaluated serum from patients with various subtypes of JIA to investigate the presence of anti-deiminated (citrullinated) fibrinogen and anti-citrullinated α-enolase antibodies, and their association with RF and anti-CCP antibody isotypes.MethodsSera were obtained from 96 JIA patients, 19 systemic lupus erythematosus (SLE) patients, and 10 healthy children. All sera were measured for antibodies against citrullinated and native fibrinogen and α-enolase by an enzyme linked immunosorbent assay (ELISA). In addition, all sera were assayed for anti-CCP antibody isotypes and rheumatoid factor (RF) isotypes by ELISA. The relationship between anti-citrullinated fibrinogen and anti-α-enolase antibodies and disease activity and joint damage were also investigated. All results were correlated with clinical and laboratory parameters using Spearman's rho correlation coefficient. Multiple logistic regression analysis was utilized to identify which variables were associated with joint erosions and diagnosis of JIA.ResultsThirty-one JIA patients (32%) demonstrated reactivity to citrullinated fibrinogen and 9 (9%) to citrullinated α-enolase. Reactivity to citrullinated fibrinogen and α-enolase was predominantly found in IgM RF-positive polyarthritis patients. Fourteen JIA patients reacted with native α-enolase and a higher percentage of SLE patients reacted with citrullinated α-enolase when compared to JIA patients. Anti-citrullinated fibrinogen antibodies correlated with the presence of IgG anti-CCP antibodies and IgA and IgM RF. The presence of anti-citrullinated α-enolase antibodies correlated with IgA anti-CCP antibodies. IgG anti-CCP antibodies were significantly associated with joint damage and anti-citrullinated fibrinogen antibodies were strongly associated with JIA when compared to control groups. Anti-citrullinated fibrinogen antibodies demonstrated high sensitivity (81%) for IgM RF-positive polyarticular JIA. IgG anti-CCP antibodies had the highest specificity (95%) for JIA, with anti-citrullinated fibrinogen antibodies, IgA anti-CCP antibodies and IgA RF all following at 84%.ConclusionsJIA patient sera exhibited strong reactivity to anti-citrullinated fibrinogen antibodies and demonstrated high sensitivity and specificity for JIA, primarily in IgM RF-positive polyarthritis patients. Fibrinogen is one of several protein targets for citrullination in JIA.

IgM, but not IgA rheumatoid factor interferes with anti-cardiolipin and anti-β2 glycoprotein I measurements: a quantitative analysis

IgM rheumatoid factor (RF) is sometimes referred to as capable of causing interference in the IgM anti-cardiolipin (aCL) testing. Published guidelines are, however, inconsistent, and evidence regarding the interference is limited. Our goal was investigate IgM and IgA RF cross-reactivity and/or interference in IgM and IgA aCL and anti-β2 glycoprotein I (aβ2GPI) testing. Serum specimens with high IgM and IgA RF levels were tested for IgG, IgA and IgM aCL and aβ2GPI antibodies to examine cross-reactivity. Samples containing IgG aCL and aβ2GPI antibodies were spiked with IgM (and IgA) RF, and samples with high RF levels were spiked with IgG aCL antibodies. The mixtures were tested for IgM and IgA aCL and aβ2GPI antibodies. Specimens with high IgM and IgA RF concentrations did not test positive for IgM or IgA aCL and aβ2GPI antibodies (except one weak positive IgA aβ2GPI result), indicating the lack of cross-reactivity. In the spiked specimens, addition of IgM RF caused significant positive bias in the measurement of both aCL and aβ2GPI antibodies of IgM isotype in the presence of IgG aCL and aβ2GPI antibodies. The threshold for triggering significant interference was 318( )IU/ml for IgM RF, and 77 GPLU/ml for IgG aCL. Neither IgM, nor IgA RF, however, affected the IgA antiphospholipid (aPL) antibody testing. IgM RF can cause a false-positive IgM aCL result in the presence of IgG aCL antibodies. In studies on the prevalence and clinical significance of IgM aPL antibodies, RF interference should be considered and RF testing should be performed.

Anti-cyclic citrullinated peptide and IgM and IgA rheumatoid factor in Sudanese patients with rheumatoid arthritis

Anti-cyclic citrullinated peptide and IgM and IgA rheumatoid factor in Sudanese patients with rheumatoid arthritis

Isotypes of anticyclic citrullinated peptide and IgM and IgA rheumatoid factor in Sudanese patients with rheumatoid arthritis

Rheumatoid arthritis (RA) is characterised by chronic, erosive polyarthritis and by the presence of various autoantibodies. According to our knowledge there are no data published concerning serologic RA phenotypes in...

Does testing for circulating autoantibodies against disease-relevant citrullinated antigens add value to the CCP2 assay in diagnosing RA among early undifferentiated arthritis patients?

BackgroundThe antigen substrates employed in the widely-used CCP2 assay do not correspond to in vivo-generated citrullinated proteins so far implicated in the potential pathogenesis of rheumatoid arthritis (RA). We assessed...

Serum IgA rheumatoid factor and pyridinoline in very early arthritis as predictors of erosion(s) at two years: A simple model of prediction from a conservatively treated community‐based inception cohort

To identify, in conservatively treated, very early arthritis patients, predictors of ≥1 erosion(s) at 2 years, and to construct a prediction model. Community-based adults (n=310) who had never taken disease-modifying antirheumatic drugs (DMARDs) or steroids with swelling of ≥2 joints persisting for >4 weeks and lasting <6 months were recruited. Erosion status was assessed at 0, 6, 12, and 24 months; evaluations were comprised of clinical criteria (Disease Activity Score, Health Assessment Questionnaire), C-reactive protein level, erythrocyte sedimentation rate, autoantibodies, bone and cartilage markers, hand densitometry, and HLA class II shared epitopes. Patients meeting American College of Rheumatology rheumatoid arthritis (RA) criteria or with undifferentiated arthritis (UA) were followed and treated conservatively: one-third of RA patients and three-fourths of UA patients received no DMARDs during 2 years; a biologic agent was given to 1.8% of the patients during the first year. The main judgment criterion was ≥1 erosion(s) at 2 years. At 2 years, 219 patients were assessed; 31.3% with RA and 10.6% with UA had ≥1 erosion(s). Logistic regression analysis at that time showed erosion(s) strongly associated with serum IgA rheumatoid factor (IgA-RF) and pyridinoline levels for the 190 patients with no baseline erosions, with the corresponding receiver operating characteristic curve having an area under the curve of 0.77 (95% confidence interval 0.64-0.86). A prediction model was constructed with IgA-RF thresholds of 5 and 25 IU/ml and a pyridinoline threshold of 10 nM/liter; odds ratios ranged from 1 for IgA-RF<5 IU/ml and pyridinoline <10 nM/liter to 50.75 for the association of IgA-RF≥5 IU/ml and pyridinoline≥10 nM/liter. This model, using serum IgA-RF and pyridinoline concentrations, was able to predict≥1 erosion(s) at 2 years in very early arthritis patients.

Serum levels of anti-CCP antibodies, anti-MCV antibodies and RF IgA in the follow-up of patients with rheumatoid arthritis treated with rituximab

Rheumatoid arthritis (RA) is characterized by the presence of circulating rheumatoid factor (RF) and anticitrullinated peptide antibodies (ACPA), which are positive in about 70–80% of patients. APCA have a higher specificity and therefore a higher diagnostic power than RF, but are less informative than RF in monitoring the course of the disease in patients under treatment. Recently, it has been reported that the anticitrullinated vimentin (a-MCV) antibody test can identify a particular subgroup of APCA that may be negative for anticyclic citrullinated peptide (a-CCP) antibodies. Concerning RF, the RF IgA isotype has been described as a more specific marker of erosive joint damage than total RF. The aim of our study was to monitor the levels of a-CCP, a-MCV, total RF and RF IgA in the follow-up of patients with RA treated with B-lymphocytedepletive rituximab (RTX), to detect any differences or peculiarities in patterns of these autoantibodies, especially in relation to their potential use as predictive markers of therapeutic response. We studied 30 patients with RA treated with RTX. All patients were previously unresponsive to at least 6 months of therapy with disease-modifying antirheumatic drugs (DMARDs; methotrexate, leflunomide, cyclosporine, chloroquine) and/or at least 6 months of therapy with anti-TNF biologics. The evaluation of response to RTX was made at month +6 using the EULAR criteria (DAS28). a-CCP, a-MCV, total RF and RF IgA were determined at baseline (before the first infusion of RTX) and after 1, 3 and 6 months. In serum samples obtained before treatment two cytokines essential for Blymphocyte proliferation, interleukin 6 (IL-6) and B-lymphocyte stimulator (BLyS) were also determined. In all patients a significant and consistent reduction in all the tested antibodies was found during follow-up, with no differences in respect of the degree of response to RTX. Of note, at baseline, generally a higher titre of all autoantibodies was seen in patients who then showed a better response to RTX. Finally, there were no differences in serum concentrations of IL-6 and BLyS in patients in relation to the presence or absence of the autoantibodies investigated, nor was there any significant correlation between the serum concentrations of the cytokines and the titres of the autoantibodies. Thus, neither a-MCV compared to a- CCP, nor RF IgA compared to routine total RF, provided any additional predictive information in the follow-up of patients with RA treated with RTX.