Rheumatoid Factor Activity Research Articles

A stereotyped light chain may shape virus-specific B-cell receptors in HCV-dependent lymphoproliferative disorders

Hepatitis C virus (HCV) causes B-cell lymphoproliferative disorders (LPDs) expressing stereotyped B-cell receptors (BCRs) endowed with rheumatoid factor (RF) activity and putatively recognizing the HCV E2 protein. To further untangle the shaping and function of these BCRs, we analyzed immunoglobulin gene rearrangements of monoclonal B cells from 13 patients with HCV-associated LPDs and correlated their features with the clinical outcomes of antiviral therapy. While only two patients shared a stereotyped heavy-chain complementarity determining region 3 (CDR3) sequence, two kappa chain CDR3 stereotyped sequences accounted for 77% of BCRs. Light chains were enriched in sequences homologous to anti-HCV E2 antibodies compared with heavy chains (7/13 vs. 0/13; p = 0.005). Anti-HCV E2 homology was uniquely associated (7/7 vs. 0/6; p = 0.0006) with a stereotyped CDR3 sequence encoded by IGKV3-20/3D-20 gene(s) accounting for 54% of BCRs. An IGKV3-15/IGKJ1-encoded stereotyped sequence homologous to WA RF accounted for 23% of BCRs. LPDs expressing KCDR3s homologous to anti-HCV E2 antibodies responded more frequently to the eradication of HCV by antiviral therapy (6/6 vs. 1/6; p = 0.015). These findings, although limited by the small sample size, suggest that a stereotyped KCDR3 may predominantly shape anti-HCV specificity of BCRs, possibly providing a signature that may help identifying bona fide HCV-dependent LPDs.

A novel mass spectrometric-based proteomic approach challenges the current paradigm on cryoglobulin typing in the diagnostic laboratory

Cryoglobulins precipitate out of serum at temperatures lower than 37°C and can have serious clinical manifestations. They may be associated with haematological malignancies, chronic infections and autoimmune diseases. Traditional typing of cryoglobulins use the Brouet classification, depending on the presence or not of rheumatoid factor activity: type I (monoclonal immunoglobulin with no rheumatoid factor), type II (mixed cryoglobulin with monoclonal rheumatoid factor) and type III (mixed cryoglobulin with polyclonal rheumatoid factor). Current methods used to type cryoglobulins include electrophoresis and immunofixation. We describe a novel, streamlined workflow of cryoglobulin analysis using mass spectrometry (MS) to characterise the proteomic signatures [heavy chain complementarity-determining region 3 (HCDR3) regions] of cryoglobulins. This provides an extension to traditional immunochemical methods of analysis and offers increased sensitivity; monitoring capacity by HCDR3 regions at the amino acid level; and clinical applications. Outstandingly, MS analysis offers predictive value by detecting the presence of pathogenic clonotypes before the onset of clinical manifestations. We highlight its applicability and benefits through clinical cases, demonstrating the greater ability to molecularly characterise cryoprecipitates in a similar turn-around time to current methodology. Work to establish clinically relevant libraries of antibody clonotypes is currently underway.

Anti-citrullinated peptide antibodies in rheumatoid arthritis patients exposed to wood smoke

<abstract><sec> <title>Background and Aims</title> <p>Rheumatoid arthritis (RA) is a chronic, systemic, autoimmune disease with an unknown etiology, which attacks the synovial tissue more than any other organ. Citrulline has been observed in the joints of RA patients. Anti-citrullinated peptide antibodies (ACPAs), which are recognized as the most specific serologic markers of RA, are synthesized against unusual citrullinated peptides during the disease. There is little information about the increased production of antibodies against citrullinated peptides in RA patients exposed to wood smoke. Therefore, in this study, we aimed to compare the serum level of ACPA in two groups of exposed and non-exposed RA patients to wood smoke.</p> </sec><sec> <title>Materials and Methods</title> <p>A total of 110 RA patients, including 55 exposed patients to wood smoke and 55 non-exposed patients, were enrolled in this study. The serum level of ACPA, rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), and disease activity (based on the 28-joint Disease Activity Score) were determined in patients and compared between the two groups.</p> </sec><sec> <title>Results</title> <p>In this study, there was no significant difference in the serum level of ACPA between the exposed and non-exposed groups (P = 0.73). On the other hand, RF (P = 0.03), ESR (P = 0.007), and disease activity index (P = 0.01) were significantly higher in the exposed group, compared to the non-exposed group.</p> </sec><sec> <title>Conclusion</title> <p>According to the results of the current study, pollutants from wood smoke significantly increased the RF, ESR, and disease activity index in RA patients. Nonetheless, there was no significant difference in the serum level of ACPA between the two groups.</p> </sec></abstract>

TLR9 signalling in HCV-associated atypical memory B cells triggers Th1 and rheumatoid factor autoantibody responses

Hepatitis C virus (HCV) infection contributes to the development of autoimmune disorders such as cryoglobulinaemia vasculitis (CV). However, it remains unclear why only some individuals with HCV develop HCV-associated CV (HCV-CV). HCV-CV is characterized by the expansion of anergic CD19+CD27+CD21low/- atypical memory B cells (AtMs). Herein, we report the mechanisms by which AtMs participate in HCV-associated autoimmunity. The phenotype and function of peripheral AtMs were studied by multicolour flow cytometry and co-culture assays with effector T cells and regulatory T cells in 20 patients with HCV-CV, 10 chronicallyHCV-infected patients without CV and 8 healthy donors. We performed gene expression profile analysis of AtMs stimulated or not by TLR9. Immunoglobulin gene repertoire and antibody reactivity profiles of AtM-expressing IgM antibodies were analysed following single B cell FACS sorting and expression-cloning of monoclonal antibodies. The Tbet+CD11c+CD27+CD21- AtM population is expanded in patients with HCV-CV compared to HCV controls without CV. TLR9 activation of AtMs induces a specific transcriptional signature centred on TNFα overexpression, and an enhanced secretion of TNFα and rheumatoid factor-type IgMs in patients with HCV-CV. AtMs stimulated through TLR9 promote type 1 effector T cell activation and reduce the proliferation of CD4+CD25hiCD127-/lowFoxP3+ regulatory T cells. AtM expansions display intraclonal diversity with immunoglobulin features of antigen-driven maturation. AtM-derived IgM monoclonal antibodies do not react against ubiquitous autoantigens or HCV antigens including NS3 and E2 proteins. Rather, AtM-derived antibodies possess rheumatoid factor activity and target unique epitopes on the human IgG-Fc region. Our data strongly suggest a central role for TLR9 activation of AtMs in driving HCV-CV autoimmunity through rheumatoid factor production and type 1 T cell responses. B cells are best known for their capacity to produce antibodies, which often play a deleterious role in the development of autoimmune diseases. During chronic hepatitis C, self-reactive B cells proliferate and can be responsible for autoimmune symptoms (arthritis, purpura, neuropathy, renal disease) and/or lymphoma. Direct-acting antiviral therapy clears the hepatitis C virus and eliminates deleterious B cells.

Dry eye in rheumatoid arthritis patients: Correlation with disease activity

Introduction and Objectives: Dry eye is a very common disorder of tear film resulting from either decreased tear production or increased tear evaporation. Rheumatoid arthritis is a well-known risk factor for dry eye occurrence. This study was undertaken to assess dry eye prevalence in rheumatoid arthritis patients and assess its correlation with disease activity. Materials and Methods: The study period was one year. Seventy patients diagnosed to have rheumatoid arthritis were enrolled in this study. They were given an OSDI questionnaire, examined for signs of dry eye and subjected to four tests (Schirmer test, TBUT, rose bengal test, Impression cytology), based on which they were labelled as being positive or negative for dry eye. The arthritis disease activity was determined using DAS score. Results: Dry eye prevalence in rheumatoid arthritis was found to be 48.5%. OSDI scores were found to correlate well with diagnostic tests done for dry eye only when they were high indicating poor correlation between signs and symptoms in early stages. Prevalence increased with increase in age of patients. There was no correlation between the occurrence of dry eye and duration of rheumatoid arthritis, rheumatoid factor or arthritis disease activity. Conclusion: Prevalence of dry eye is high in rheumatoid arthritis patients. OSDI questionnaire is a useful screening tool for dry eye. Impression cytology is an easy and useful test to assess surface changes in dry eye patients. Keywords: Disease activity, Dry eye, Impression cytology, OSDI, Rheumatoid arthritis.

CTHRC1: A New Candidate Biomarker for Improved Rheumatoid Arthritis Diagnosis.

Background: The purpose of this study was to determine whether plasma levels of the collagen triple helix repeat containing 1 (CTHRC1) protein can serve as a blood-based biomarker for improved diagnosis of rheumatoid arthritis (RA) patients and monitoring of RA disease activity.Methods: We measured levels of CTHRC1 in the plasma of patients diagnosed with RA, osteoarthritis (OA), reactive arthritis (ReA), as well as in healthy individuals. We then assessed the correlation between CTHRC1 protein and a range of indices including the 28-joint disease activity score (DAS28), rheumatoid factor (RF), C-reactive protein (CRP), anti-citrullinated protein antibodies (ACPA), erythrocyte sedimentation rate (ESR), as well as a panel of cytokines, including interleukin 1 beta (IL-1β), interleukin 6 (IL-6), interleukin 8 (IL-8), and interferon gamma (IFNγ). Receiver operating characteristic (ROC) analysis was further performed to assess the diagnostic value of CTHRC1.Results: CTHRC1 plasma levels were significantly elevated in RA patients compared to healthy individuals, OA and ReA patients. ROC curve and risk score analysis suggested that plasma CTHRC1 can accurately discriminate patients with RA from healthy controls and may have practical value for RA diagnosis. CTHRC1 levels were positively associated with RF, ACPA, CRP, and disease activity based on the combined index of DAS28 with CRP (DAS28-CRP), and also strongly correlated with IL-1β, IL-6, IL-8, and IFNγ.Conclusion: Our studies show that CTHRC1 is a sensitive and easy-to-measure plasma marker that differentiates between RA and healthy status and also distinguishes between RA and other forms of arthritis, such as OA and ReA. At the current level of understanding, plasma CTHRC1 levels may improve the diagnosis of RA and these findings warrant confirmation in a larger, more comprehensive patient population.

Expression of CD62P and CD154 in peripheral blood of patients with rheumatoid arthritis and their correlation with clinical indexes

The aim of this study is to investigate the expression of CD62P and CD154 in peripheral blood of patients with rheumatoid arthritis (RA) and their correlation with the clinical indexes of RA. A total of 60 RA patients diagnosed and treated in the Department of Rheumatism in our hospital from January to December 2016 were selected as the RA group, and 60 cases of healthy subjects were selected as the control group. CD62P and CD154 levels in peripheral blood were determined by flow cytometry using the FACS Vantage flow cytometer, and the correlation analysis with the clinical indexes of RA patients were conducted. The levels of CD62P and CD154 in the peripheral blood of RA group were 28.75% ± 1.48% and 26.84% ± 1.03%, respectively, which were significantly higher than those of the control group ( P < 0.05). The levels of white blood cell (WBC), platelet (PLT), erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), C-reactive protein (CRP), and interleukin (IL)-37 in the RA group were significantly higher than those in the control group ( P < 0.05). Pearson test showed that CD62P and CD154 levels in the peripheral blood in the RA group were positively correlated with serum WBC, PLT, ESR, RF, CRP, IL-37, and disease activity score 28 (DAS28) ( P < 0.05), but not correlated with disease course ( P > 0.05). The expression of CD62P and CD154 in peripheral blood of patients with RA was upregulated, and their expression levels were correlated with the activity of RA and the degree of joint lesion.

Cyclophosphamide in a cohort of biologic naïve rheumatoid arthritis patients resistant to conventional DMARDs

Background: Rheumatoid Arthritis (RA) poses a significant economic burden in health services worldwide. The most important factor influences poor outcome in RA patients is the lack of drug adherence that is mainly due to financial cost and poor patient education. There is a significant number of RA patients fail to respond or show poor response to conventional DMARDs and they can’t afford the high cost of biologic therapy. Cyclophosphamide (CYC) is an immunosuppressive drug that inhibit the actively dividing inflammatory cells, suppressing the inflammatory cytokines and stops inflammation induced joint erosions in RA patients. To evaluate the efficacy of IV pulse methylprednisolone (MP) and Cyclophosphamide (CYC) in induction of remission in a cohort biologic naive aggressive RA patients resistant to different combinations of conventional Disease-Modifying Anti Rheumatic Drugs (DMARDs). Methods and Findings: A prospective observational study performed on 30 RA patients diagnosed according to American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria, who fail to respond to different combinations of conventional DMARDs for at least two years. All patients subjected to history taking, rheumatological examination, assessment of RA disease activity, laboratory investigations; Complete Blood Count (CBC), Erythrocyte Sedimentation Rate (ESR), C-Reactive Protein (CRP), Rheumatoid Factor (RF) and anti-cyclic citrullinated peptide antibody (ACCP) recorded at baseline and after 6 months (study endpoint). All RA patients have been treated with monthly IV pulse 1 g MP and CYC at a dose 500 mg/m2 surface area for 6 months. On comparing baseline to endpoint data there was a significant reduction in all disease activity parameters: number of tender and swollen joints, disease activity scores 28 (DAS28), Health Assessment Questionnaire (HAQ), Visual Analog Scale (VAS), ESR, CRP and platelet (PLT) level, with increase in haemoglobin in all treated patients at the study endpoint. No significant difference between RF, ACCP seropositivity and different disease activity markers, except for increased haemoglobin in RF positive and reduction of PLT count in positive ACCP patients’ post-treatment. High CRP at baseline indicates poor prognosis, response to pulse CYC therapy and high VAS at the study endpoint. Conclusions: Pulse MP and CYC monthly for 6 months significantly benefit in induction of remission in a biologic naive aggressive RA patients resistant to different combinations of conventional DMARDs.

IgG cryoglobulinemia.

Mixed Cryoglobulinemia is the most well-known Hepatitis C Virus (HCV)-associated extrahepatic manifestation. MC is both an autoimmune and B-lymphoproliferative disorder. Cryoglobulins (CGs) are classified into three groups according to immunoglobulin (Ig) composition: type I is composed of one isotype or Ig class. Type II and type III mixed CGs are immune complexes composed of polyclonal IgGs acting as autoantigens and mono, polyclonal or oligoclonal IgM with rheumatoid factor activity. IgG1 and IgG3 are the predominant subclasses involved. This study shows the simultaneous presence of IgG-RF and IgG3, supporting the hypothesis of an involvement of this subclass in the initiation of early stages of CGs. We describe a case series of six HCV-positive patients, all of whom had peripheral neuropathy and transient ischemic attacks, presenting cryoprecipitates formed by IgG3 and IgG1. Cryoprecipitate IgG subclass research was carried out by immunofixation electrophoresis by using antisera against IgG1, IgG2, IgG3, and IgG4. Our six patients presented with an immunochemical pattern characterized by the mere presence of IgG1 and IgG3 subclasses with probable RF activity and one of these six patients exhibited monoclonal IgG3 in his cerebrospinal fluid. We can hypothesize that the IgG passage through the blood-brain barrier could have contributed to the cause of TIAs, through a mechanism involving the precipitation of circulating immune complexes formed by the two subclasses in the intrathecal vessels.

Treatment for hepatitis C virus-associated mixed cryoglobulinaemia.

Treatment for hepatitis C virus-associated mixed cryoglobulinaemia.

Structure–function analyses of a stereotypic rheumatoid factor unravel the structural basis for germline-encoded antibody autoreactivity

Rheumatoid factors (RFs) are autoantibodies against the fragment-crystallizable (Fc) region of IgG. In individuals with hematological diseases such as cryoglobulinemia and certain B cell lymphoma forms, the RFs derived from specific heavy- and light-chain germline pairs, so-called "stereotypic RFs," are frequently produced in copious amounts and form immune complexes with IgG in serum. Of note, many structural details of the antigen recognition mechanisms in RFs are unclear. Here we report the crystal structure of the RF YES8c derived from the IGHV1-69/IGKV3-20 germline pair, the most common of the stereotypic RFs, in complex with human IgG1-Fc at 2.8 Å resolution. We observed that YES8c binds to the CH2-CH3 elbow in the canonical antigen-binding manner involving a large antigen-antibody interface. On the basis of this observation, combined with mutational analyses, we propose a recognition mechanism common to IGHV1-69/IGKV3-20 RFs: (1) the interaction of the Leu432-His435 region of Fc enables the highly variable complementarity-determining region (CDR)-H3 to participate in the binding, (2) the hydrophobic tip in the CDR-H2 typical of IGHV1-69 antibodies recognizes the hydrophobic patch on Fc, and (3) the interaction of the highly conserved RF light chain with Fc is important for RF activity. These features may determine the putative epitope common to the IGHV1-69/IGKV3-20 RFs. We also showed that some mutations in the binding site of RF increase the affinity to Fc, which may aggravate hematological diseases. Our findings unravel the structural basis for germline-encoded antibody autoreactivity.

Identification of novel biomarker as citrullinated inter-alpha-trypsin inhibitor heavy chain 4, specifically increased in sera with experimental and rheumatoid arthritis

BackgroundAnticitrullinated protein antibodies (ACPA) and citrullinated proteins play key roles in the pathogenesis of rheumatoid arthritis (RA). Many candidate citrullinated antigens have been identified in joints, but citrullinated proteins in sera are mostly uncertain in patients with RA. We explored the expression of citrullinated proteins in joints and sera of experimental arthritis, and we further investigated their specific expression correlated with the disease activity in patients with RA.MethodsCitrullinated protein expression in tissues was examined by IHC in peptide glucose-6-phosphate isomerase-induced arthritis (pGIA). Serum citrullinated proteins from pGIA were examined by Western blotting, and the sequence was identified by MS. With the same methods, serum citrullinated proteins were analyzed in patients with RA, primary Sjögren’s syndrome, systemic lupus erythematosus, and osteoarthritis as well as in healthy subjects, by Western blotting and MS. In patients with RA, the relationship between the expression of the identified protein (inter-alpha-trypsin inhibitor heavy chain 4 [ITIH4]) and clinical features was evaluated, and the levels of citrullinated ITIH4 were compared before and after biological treatment. The antibody response against citrullinated ITIH4 peptide was measured by enzyme-linked immunosorbent assay.ResultsCitrullinated proteins were detected specifically in arthritic joints and sera from pGIA relative to controls. In sera, a common band of citrullinated protein at 120 kDa was revealed, and it fluctuated in parallel with arthritis score of pGIA by Western blotting. Interestingly, in 82% of RA patient sera, similar bands of citrullinated protein were specifically detected. These proteins were identified as citrullinated ITIH4, and especially the R438 site was commonly citrullinated between mice and humans. Citrullinated ITIH4 levels were associated with clinical parameters such as C-reactive protein (CRP), rheumatoid factor, and Disease Activity Score in 28 joints as measured by CRP in patients with RA. Its levels were decreased in correlation with the reduction of disease activity score after effective treatment in patients with RA. Moreover, antibody response to citrullinated epitope in ITIH4 was specifically observed in patients with RA.ConclusionsOur results suggest that serum citrullinated ITIH4 was specifically increased in patients with RA and could be a novel biomarker for assessing disease activity in patients with RA.

Different biochemical patterns in type II and type III mixed cryoglobulinemia in HCV positive patients

BackgroundReversible cryoprecipitability of proteins is observed as a concomitant feature of immune complex formation. Mixed cryoglobulinemia (MC) is systemic vasculitis, associated with mixed IgM and IgG cryoglobulins (CGs) showing rheumatoid factor (RF) activity. It is frequently associated with hepatitis C virus (HCV). This study investigates the presence of IgG RF and anti-nuclear antibodies (ANA) in cryoprecipitates of patients with type III and type II MC, to understand the biochemical patterns associated with different types of MC to a greater degree. MethodsSera from 70 HCV untreated patients with type III or type II MC were tested by immunofixation for IgG3 and through ELISA for IgG RF. Cryoprecipitates were analysed for ANA by indirect immunofluorescence to identify specific patterns. ResultsAfter stratification according to MC type, the ANA patterns between type II and type III MC were statistically different. IgG3 levels and IgG-RF positivity were significantly higher in type III cryoprecipitate. We observed a higher positivity of IgG3 and a significant difference between the liver fibrosis stage, ANA and IgG-RF in the cryoprecipitate. ConclusionResults show a combination of biochemical markers and autoantibodies associated to mixed cryoglobulinemia; these findings could be further investigated in order to ascertain their usefulness in assessing the risk for the development of mixed cryoglobulinemia.

Direct-acting antiviral agents in the therapy of hepatitis C virus-related mixed cryoglobulinaemia: a single-centre experience

BackgroundThe efficacy and safety of direct-acting antiviral agents (DAAs) were evaluated in a cohort of prospectively enrolled patients with hepatitis C virus (HCV)-related mixed cryoglobulinaemia (MC), an immune complex-mediated vasculitis of small and medium vessels in which the pathogenetic role of HCV has been clearly established.MethodsTwenty-two patients received DAAs. Clinical and laboratory features were recorded at baseline, every 4 weeks until the end of treatment (EoT), and 12 weeks afterwards. Primary efficacy endpoints were (a) sustained virological response 12 weeks after therapy completion (SVR12), (b) regression of symptomatology (clinical response) and (c) cryoglobulin disappearance or cryocrit reduction ≥50% (immunological response). Complete response (CR) was defined as the occurrence of all three primary endpoints; partial response (PR) was defined as the occurrence of SVR12, with or without either immunological or clinical response; and no response was defined as missing the achievement of all three endpoints.ResultsAll patients reached SVR12. Compared with basal values, mean cryocrit values were significantly decreased at EoT and SVR12. A significant reduction of alanine transaminase and a parallel increase of complement component C4 levels were also detected. Rheumatoid factor activity was significantly reduced at EoT but not at SVR12. At SVR12, a CR was established in 14 patients (63.7%) and a PR in 8 patients (36.3%). In one patient with small lymphocytic lymphoma, the tumour progressed despite viral clearance. Mild adverse events were recorded in nine patients (40.9%).ConclusionsThe response rates induced by the use of DAAs in patients with MC were remarkably higher than those previously achieved with pegylated interferon-α/ribavirin, with or without rituximab. A much longer follow-up is desirable to achieve useful information in terms of persistent viral clearance and clinical response.

Efficacy and Safety of Sofosbuvir Plus Daclatasvir for Treatment of HCV-Associated Cryoglobulinemia Vasculitis

Circulating mixed cryoglobulins are detected in 40%-60% of patients with hepatitis C virus (HCV) infection, and overt cryoglobulinemia vasculitis (CryoVas) develops in approximately 15% of patients. Remission of vasculitis has been associated with viral clearance, but few studies have reported the effectiveness of direct-acting antiviral drugs in these patients. We performed an open-label, prospective, multicenter study of the effectiveness and tolerance of an all-oral, interferon- and ribavirin-free regimen of sofosbuvir plus daclatasvir in patients with HCV-associated CryoVas. Forty-one consecutive patients with active HCV-associated CryoVas (median age, 56 y; 53.6% women) were recruited from hospitals in Paris, France, from 2014 through 2016. They received sofosbuvir (400 mg/day) plus daclatasvir (60 mg/day) for 12 weeks (n= 32) or 24 weeks (n= 9), and were evaluated every 4 weeks until week 24 and at week 36. Blood samples were analyzed for complete blood count, serum chemistry profile, level of alanine aminotransferase, rheumatoid factor activity, C4 fraction of complement, and cryoglobulin; peripheral blood mononuclear cells were isolated for flow cytometry analysis. Thirty-seven patients (90.2%) had a complete clinical response (defined by improvement of all the affected organs involved at baseline and no clinical relapse) after a median time of 12 weeks of therapy; all had a sustained virologic response (no detectable serum HCV RNA 12 weeks after the end of antiviral therapy). Patients' mean cryoglobulin level decreased from 0.56 ± 0.18 at baseline to 0.21 ± 0.14 g/L at week 36, and no cryoglobulin was detected in 50% of patients at this time point. After antiviral therapy, patients had increased numbers of T-regulatory cells, IgM+CD21-/low-memory B cells, CD4+CXCR5+ interleukin 21+ cells, and T-helper 17 cells, compared with before therapy. After a median follow-up period of 26 months (interquartile range, 20-30 mo), no patients had a serious adverse event or relapse of vasculitis.

Rheumatoid Factor as a Potentiator of Anti-Citrullinated Protein Antibody-Mediated Inflammation in Early Undifferentiated Seronegative Osteoarthropathy

Abstract Introduction. To compare the values and accuracy of the test in anticyclic citrullinated peptides antibodies, rheumatoid factor (RF), C-reactive protein (CRP) and disease activity index in early diagnosis of untreated psoriatic arthritis (PsA). Methods. Using the ELISA method of DIA-STATTM Anti CCP (Axis-Shield Diagnostics), sera of 70 participants were examined (35 untreated patients with PsA and 35 subjects from the healthy control group). RF and CRP were determined with the agglutination test (latex test). At the same time the sensitivity, specificity, predictive value for positive and negative testsand accuracy were determined. Results. Of 35 patientswith PsA, 1 patient showed presence of anti-CCP antibodies (sensitivity test 2.86%), while RF was foundin 0 patients(sensitivity test 0%). In the healthy control group positivevalues for RF, CRP and erythrocyte sedimentation rate were detected in 1 patient. Conclusion. ACPA antibodies have low sensitivity, but high specificity in PsA.

Some Aspect of Accuracy of Acpa Assay in Patients with Psoriatic Arthritis

Aims:To compare the values and acuracy of the test in anticyclic citrullinatedpeptides (Anti-CCP /ACPA) antibodies, Rheumatoid factor (RF), C-Reactive Protein (CRP) and disease activity index (PASI) in early diagnosis of untreated Psoriatic arthritis(PsA).Methods:Using the ELISA method of DIA-STATTM Anti CCP (Axis–Shield Diagnostics), sera of 70 participants were examined (35 untreated patients with PsA and 35 persons from the healthy control group). RF and CRP were determined with the agglutination test (Lateks test) in the same participants. In the same time we determined the sensitivity, specificity, predictive value for positive and negative test and accuracy.Results:From 35 pts with PsA, 1 patient showed presence of Anti-CCP antibodies (sensitivity test 2.86%), while RF was present in 0 pts (sensitivity test 0%). In the healthy control group positive values for RF, CRP and Erythroid Sedimentation Rate (ESR) were detected in 1 participant.Conclussion:ACPA antibodies have low sensitivity, but high specificity in PsA.Key words: Anti cyclic citrullinated peptide (Anti-CCP) Psoriatic arthritis (PsA), Rheumatoid factor (RF)

Clinical Relevance and Evaluation of the Antibodies against Cyclic Citrullinated Peptide as Overall Test in Undiferentiated Psoriatic Arthropathy Sine Psoriasis Vulgaris with or without Joint Inflammation

Aims: To compare the values and acuracy of the test in anticyclic citrullinated peptides (Anti-CCP /ACPA) antibodies, Rheumatoid factor (RF), C-Reactive Protein (CRP) and disease activity index (PASI) in early diagnosis of untreated Psoriatic arthritis (PsA). Methods: Using the ELISA method of DIA-STATTM Anti CCP (Axis–Shield Diagnostics), sera of 70 participants were examined (35 untreated patients with PsA and 35 persons from the healthy control group). RF and CRP were determined with the agglutination test (Latex test) in the same participants. In the same time we determined the sensitivity, specificity, predictive value for positive and negative test and accuracy. Results: From 35 pts with PsA, 1 patient showed presence of Anti-CCP antibodies (sensitivity test 2.86%), while RF was present in 0 pts (sensitivity test 0%). In the healthy control group positive values for RF, CRP and erythrocyte sedimentation rate (ESR) were detected in 1 participant. Conclussion: ACPA antibodies have low sensitivity, but high specificity in PsA. Keywords: Anti cyclic citrullinated peptide; Psoriatic arthritis; Rheumatoid factor.

Relationship between asymmetric dimethylarginine and endothelial dysfunction in patients with rheumatoid arthritis.

In rheumatoid arthritis (RA), endothelial dysfunction caused by the inflammatory process increases the risk of cardiovascular disease. Asymmetric Dimethylarginine (ADMA) leads to vascular dysfunction, whereas atherosclerosis and increased ADMA is associated with cardiovascular disease risk factors. Flow-mediated Dilation (FMD) is a radiological method to demonstrate endothelial dysfunction. In the present study, we assessed the availability of ADMA as a marker for endothelial dysfunction in RA patients. ADMA can be used as a simple and cheaper method for the determination of endothelial dysfunction. Forty patients (1 male, 39 female) diagnosed with RA according to the classification criteria and 29 healthy volunteers (2 males, 27 females) were included in this study. ADMA was studied by enzyme-linked immunosorbent assay (ELISA). Chi-square, Fisher's exact test, Mann-Whitney U test, and Spearman's correlation tests were used for analytical analysis, and p<0.05 was considered as the level of statistical significance. In our study, ADMA levels were significantly higher in RA patients. The ADMA level was inversely correlated with FMD. Although high levels of both C-reactive protein and ADMA were detected in patients with high disease activity, there was no statistically significant difference between these parameters (p=0.18). There were statistically significant negative correlations between FMD and age and disease duration (p=0.01, p=0.01). However, there were no statistically significant correlations with erythrocyte sedimentation rate, rheumatoid factor, and disease activity score (p=0.68). In RA patients, there was a statistically significant positive correlation between disease duration and ADMA, whereas a negative correlation was found between FMD and ADMA (p<0.05). Our results support the hypothesis that ADMA may be used in the assessment of endothelial dysfunction in patients with RA. It will be cost-effective when commonly used. ADMA may be used in the assessment of endothelial dysfunction in patients with RA.

Rheumatoid Factor and Disease Activity Are Independent Predictors of Lymphoma in Primary Sjögren's Syndrome.

To define parameters predictive of lymphoma development in patients with primary Sjögren's syndrome (SS). A multicenter case-control survey was performed to identify predictors of lymphoma. Cases were patients who developed lymphoma after diagnosis of primary SS and were mainly recruited through the Club Rhumatismes et Inflammation network. For each case, 2 controls (matched for disease duration and age) were randomly selected among patients with primary SS and without lymphoma. Cases and controls were compared using univariate analysis and then using multivariate analysis to identify independent predictors of lymphoma. One hundred one patients with primary SS and lymphoma were included. Eighty-seven patients were women (86.1%), and the mean ± SD age at lymphoma diagnosis was 57.4 ± 12.6 years. The most frequent histologic type was B cell non-Hodgkin's lymphoma (NHL) in 99 of 101 patients, with marginal-zone lymphoma in 76 of the 99 patients (76.8%) including 58 (58.6%) with lymphoma of the mucosa-associated lymphoid tissue type. Lymphomas were most frequently located in the salivary glands (43 patients). A specific treatment was initiated at diagnosis in 87 patients with B cell NHL, and 61 patients (61.6%) achieved complete sustained remission after the first line of treatment. In the multivariate analysis, salivary gland enlargement, the presence of rheumatoid factor (RF), low C4, cryoglobulinemia, lymphopenia, and disease activity according to the European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (excluding the lymphoma domain) were found to be predictors of lymphoma. No previous treatment for primary SS was associated with any effect on lymphoma occurrence. In addition to previously known factors predictive of lymphoma occurrence, the independent roles of RF and disease activity were demonstrated in this case-control study of primary SS-associated lymphoma. Our findings highlight the roles of chronic antigenic stimulation and disease activity in the development of this severe complication.