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Jeremy Sokolove - One of the best experts on this subject based on the ideXlab platform.
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Alveolar Bone Loss Is Associated With Circulating Anti-Citrullinated Protein Antibody (ACPA) in Patients With
2015Co-Authors: Rheumatoid Arthritis, Jeremy SokoloveAbstract:citrullinated Protein Antibody (ACPA)-positive rheumatoid arthritis (RA) patients versus control patients with osteoarthritis (OA); and 2) the association of ABL with RA disease activity and ACPA concentra-tions, including multiple antigen–specific ACPA. Methods: This multicenter case-control study includes 617 patients diagnosed with RA (n = 287) or OA (n = 330). Panoramic radiographs were taken; patients were categorized into low, moderate, or high tertiles based on mean percentage ABL. Serum ACPA was measured using second-generation anti-cyclic citrullinated peptide enzyme-linked immunosorbent assay and a multiplex platform to assess dis-tinct antigen-specific ACPA. A generalized linear mixed model for binary data was used to compare stratified ABL in RA versus OA patients. Associations of moderate and high ABL (versus low) with RA disease activity and severity measures were examined using multivariate regression. Antigen-specific ACPA responses were compared among ABL tertiles using significance analysis of microarrays. Results: ACPA-positive patients with RA had a significantly higher mean percentage of sites with ABL>20 % compared with patients with OA (P = 0.03). After multivariate adjustment, greater ABL was signif-icantly associated with higher serum ACPA concentration (P = 0.004), 28-joint Disease Activity Score (P = 0.023), health assessment questionnaire disability (P = 0.05), tender joint count (P = 0.02) and joint space narrowing scores (P = 0.05) among patients with RA. ACPAs targeting citrullinated vimentin and histone were significantly higher in moderate and high ABL groups versus low, regardless of smoking status (q <0.1%). Conclusions: Greater ABL was associated with higher ACPA, consistent with findings at articular sites. ACPA targeting could provide novel insight into important linkages between RA and periodontitis. J Periodon-tol 2015;86:222-231
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alveolar bone loss is associated with circulating anti citrullinated Protein Antibody acpa in patients with rheumatoid arthritis
Journal of Periodontology, 2015Co-Authors: Shawneen M Gonzalez, Jeffrey B Payne, Geoffrey M Thiele, Alan R Erickson, Paul G Johnson, Marian J Schmid, Grant W Cannon, Gail S Kerr, Andreas M Reimold, Jeremy SokoloveAbstract:Background: This study examines: 1) alveolar bone loss (ABL), a hallmark of periodontitis, in anti-citrullinated Protein Antibody (ACPA)-positive rheumatoid arthritis (RA) patients versus control patients with osteoarthritis (OA); and 2) the association of ABL with RA disease activity and ACPA concentrations, including multiple antigen–specific ACPA.Methods: This multicenter case-control study includes 617 patients diagnosed with RA (n = 287) or OA (n = 330). Panoramic radiographs were taken; patients were categorized into low, moderate, or high tertiles based on mean percentage ABL. Serum ACPA was measured using second-generation anticyclic citrullinated peptide enzyme-linked immunosorbent assay and a multiplex platform to assess distinct antigen-specific ACPA. A generalized linear mixed model for binary data was used to compare stratified ABL in RA versus OA patients. Associations of moderate and high ABL (versus low) with RA disease activity and severity measures were examined using multivariate regres...
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rheumatoid factor as a potentiator of anti citrullinated Protein Antibody mediated inflammation in rheumatoid arthritis
Arthritis & Rheumatism, 2014Co-Authors: Jeremy Sokolove, Geoffrey M Thiele, Andreas M Reimold, Dannette S Johnson, Lauren J Lahey, Catriona A Wagner, Danye Cheng, Kaleb Michaud, Harlan Sayles, Liron CaplanAbstract:Objective The co-occurrence of rheumatoid factor (RF) and anti–citrullinated Protein Antibody (ACPA) positivity in rheumatoid arthritis (RA) is well described. However, the mechanisms underlying the potential interaction between these 2 distinct autoantibodies have not been well defined. The aim of this study was to evaluate the epidemiologic and molecular interaction of ACPAs and RF and its association with both disease activity and measures of RA-associated inflammation. Methods In a cohort of 1,488 US veterans with RA, measures of disease activity and serum levels of cytokines and multiplex ACPAs were compared between the following groups of patients: double-negative (anti–cyclic citrullinated peptide [anti-CCP]−/RF−), anti-CCP+/RF−, anti-CCP−/RF+, or double-positive (anti-CCP+/RF+). Additional studies were performed using an in vitro immune complex (IC) stimulation assay in which macrophages were incubated with ACPA ICs in the presence or absence of monoclonal IgM-RF, and tumor necrosis factor α production measured as a readout of macrophage activation. Results Compared with the double-negative subgroup (as well as each single-positive subgroup), the double-positive subgroup exhibited higher disease activity as well as higher levels of C-reactive Protein and inflammatory cytokines (all P < 0.001). In vitro stimulation of macrophages by ACPA ICs increased cytokine production, and the addition of monoclonal IgM-RF significantly increased macrophage tumor necrosis factor α production (P = 0.003 versus ACPA ICs alone). Conclusion The combined presence of ACPAs and IgM-RF mediates increased proinflammatory cytokine production in vitro and is associated with increased systemic inflammation and disease activity in RA. Our data suggest that IgM-RF enhances the capacity of ACPA ICs to stimulate macrophage cytokine production, thereby providing a mechanistic link by which RF enhances the pathogenicity of ACPA ICs in RA.
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brief report citrullination within the atherosclerotic plaque a potential target for the anti citrullinated Protein Antibody response in rheumatoid arthritis
Arthritis & Rheumatism, 2013Co-Authors: Jeremy Sokolove, Lauren J Lahey, Matthew J Brennan, Orr Sharpe, Amy H Kao, Eswar Krishnan, Daniel Edmundowicz, Christin M Lepus, Mary Chester M Wasko, William H RobinsonAbstract:Objective To investigate whether citrullinated Proteins within the atherosclerotic plaque can be targeted by anti–citrullinated Protein antibodies (ACPAs), forming stimulatory immune complexes that propagate the progression of atherosclerosis. Methods Protein lysates prepared from atherosclerotic segments of human aorta were assessed for the presence of citrulline-modified Proteins, and specifically citrullinated fibrinogen (Cit-fibrinogen), by immunoprecipitation and/or immunoblotting followed by mass spectrometry. Immunohistochemical analysis of coronary artery plaque was performed to determine the presence of citrullinated Proteins and peptidylarginine deiminase type 4 (PAD-4). Serum levels of anti–cyclic citrullinated peptide (anti-CCP), anti–citrullinated vimentin (anti–Cit-vimentin), and anti–Cit-fibrinogen antibodies were measured in 134 women with seropositive rheumatoid arthritis; these subjects had previously been characterized for the presence of subclinical atherosclerosis, by electron beam computed tomography scanning. Results Western blot analysis of atherosclerotic plaque lysates demonstrated several citrullinated Proteins, and the presence of Cit-fibrinogen was confirmed by immunoprecipitation and mass spectrometry. Immunohistochemical analysis showed colocalization of citrullinated Proteins and PAD-4 within the coronary artery plaque. In age-adjusted regression models, antibodies targeting Cit-fibrinogen and Cit-vimentin, but not CCP-2, were associated with an increased aortic plaque burden. Conclusion Citrullinated Proteins are prevalent within atherosclerotic plaques, and certain ACPAs are associated with the atherosclerotic burden. These observations suggest that targeting of citrullinated epitopes, specifically Cit-fibrinogen, within atherosclerotic plaques could provide a mechanism for the accelerated atherosclerosis observed in patients with RA.
B A C Dijkmans - One of the best experts on this subject based on the ideXlab platform.
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development of the anti citrullinated Protein Antibody repertoire prior to the onset of rheumatoid arthritis
Arthritis & Rheumatism, 2011Co-Authors: Lotte A Van De Stadt, G Wolbink, R J Van De Stadt, B A C Dijkmans, Margret H M T De Koning, Dorte Hamann, Dirkjan Van SchaardenburgAbstract:Objective. To examine how anti–citrullinated Protein Antibody (ACPA) epitope spreading takes place prior to the onset of clinical rheumatoid arthritis (RA), and to analyze the pattern of autoantigen reactivity at the beginning of the immune response. Methods. Multiple consecutive serum samples from 79 RA patients who had donated blood before disease onset were available for analysis. Fifty-three patients tested positive for ACPAs prior to the onset of clinical RA. For these patients, a median of 6 (interquartile range 4–9) sequential pre-RA serum samples obtained 1–2 years apart were tested. Reactivity to 5 distinct citrullinated peptides was measured by enzymelinked immunosorbent assay. Two peptides were derived from fibrinogen, 1 from vimentin, 1 from -enolase, and 1 from filaggrin. Results. In 25 of 53 ACPA-positive patients, seroconversion from ACPA absence to ACPA presence was observed. In 72% of these patients, the immune response started with reactivity to 1 peptide, without preference for a particular peptide. The number of peptides recognized increased over time, without a dominant epitopespreading pattern. ACPAs appeared in low levels several years prior to the diagnosis of RA. Antibody titers increased markedly 2–4 years before diagnosis. Conclusion. Our findings indicate that ACPA epitope spreading occurs over several years prior to the onset of clinical RA. The initial autoimmune response is mostly directed toward only 1 autoantigen, but this is not always the same antigen. The marked increase in ACPA titers a few years prior to the diagnosis of RA suggests a second stage in disease development, which might be due to a variety of factors.
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the extent of the anti citrullinated Protein Antibody repertoire is associated with arthritis development in patients with seropositive arthralgia
Annals of the Rheumatic Diseases, 2011Co-Authors: Lotte A Van De Stadt, Ger J M Pruijn, Wouter H Bos, G Wolbink, R J Van De Stadt, B A C Dijkmans, Ann R Van Der Horst, Margret H M T De Koning, Dirkjan Van Schaardenburg, Dorte HamannAbstract:Objectives To determine the fine specificity of anti-citrullinated Protein antibodies (ACPA) in the early phase of arthritis development, the ACPA repertoire in arthralgia patients and the association with arthritis development were studied. Methods A total of 244 patients with arthralgia positive for anti-cyclic citrullinated peptide antibodies (aCCPs) and/or IgM rheumatoid factor (IgM-RF), without arthritis were included. Development of arthritis was defined as presence of one or more swollen joints at clinical examination during follow-up. Sera were tested at baseline for reactivity to five citrullinated peptides derived from fibrinogen (three), vimentin (one) and α-enolase (one) and five corresponding arginine peptides in an ELISA. Results In all, 69 patients (28%) developed arthritis in a median of 3 joints after a median follow-up of 11 (IQR 5–20) months. Reactivity to each peptide was significantly associated with arthritis development (p Conclusions Arthritis development is not associated with recognition of a specific citrullinated peptide once joint complaints are present. The ACPA repertoire in some patients with arthralgia is expanded. High aCCP levels are associated with a qualitatively broad ACPA repertoire. Patients with an extended ACPA repertoire have a higher risk of developing arthritis.
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arthritis development in patients with arthralgia is strongly associated with anti citrullinated Protein Antibody status a prospective cohort study
Annals of the Rheumatic Diseases, 2010Co-Authors: Wouter H Bos, G Wolbink, M Boers, G J Tijhuis, N De Vries, I E Van Der Horstbruinsma, Paul P Tak, R J Van De Stadt, C J Van Der Laken, B A C DijkmansAbstract:Background Anti-citrullinated Protein antibodies (ACPA) are associated with increased risk for rheumatoid arthritis. Objective To investigate the effect of the presence and levels of ACPA on arthritis development in patients with arthralgia. Methods Patients with arthralgia positive for ACPA or IgM rheumatoid factor (IgM-RF) were tested for the shared epitope (SE) and were prospectively followed up for at least 12 months. Absence of clinical arthritis at inclusion and arthritis development during follow-up were independently confirmed by two investigators. Cox regression hazard analyses were used to calculate hazard ratios (HRs) for arthritis development. Results 147 patients with arthralgia were included (50 ACPA positive, 52 IgM-RF positive and 45 positive for both antibodies). After a median follow-up of 28 months (interquartile range (IQR) 19–39), 29 patients developed arthritis in a median of 4 (IQR 3–6) joints and 26 (90%) of these were ACPA positive. The presence of ACPA (HR = 6.0; 95% confidence interval (95% CI) 1.8 to 19.8; p = 0.004), but not of IgM-RF (HR = 1.4, 95% CI 0.6 to 3.1) nor the SE (HR = 1.5, 95% CI 0.7 to 3.0), was associated with arthritis development. Within the group of ACPA-positive patients, the risk for arthritis was enhanced by the presence of IgM-RF (HR = 3.0; 95% CI 1.4 to 6.9; p = 0.01) and high ACPA levels (HR = 1.7; 95% CI 1.1 to 2.5; p = 0.008), but not the SE (HR = 1.0; 95% CI 0.5 to 2.1; p = 1.0). Conclusion In patients with arthralgia the presence of ACPA (but not of IgM-RF or SE) predicts arthritis development. The risk in ACPA-positive patients may be further increased by the concomitant presence of IgM-RF or high levels of ACPA.
Geoffrey M Thiele - One of the best experts on this subject based on the ideXlab platform.
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autoimmunity of the lung and oral mucosa in a multisystem inflammatory disease the spark that lights the fire in rheumatoid arthritis
The Journal of Allergy and Clinical Immunology, 2016Co-Authors: Ted R Mikuls, Jeffrey B Payne, Kevin D Deane, Geoffrey M ThieleAbstract:There is a growing body of evidence to suggest that autoimmunity in patients with rheumatoid arthritis (RA) is initiated outside the joint. This is supported by the observation that circulating autoantibodies, including both rheumatoid factor and anti-citrullinated Protein Antibody, can be detected in many subjects years before the development of initial joint symptoms leading to an RA diagnosis. Of the potential extra-articular sites implicated in disease initiation, mucosal tissues have garnered increasing attention. Several lines of investigation have separately implicated mucosal tissues from varying anatomic locations as possible initiating sites for RA, including those from the lung and oral cavity. In this review we summarize recent reports incriminating these mucosal tissues as the initial site of autoAntibody generation and inflammation in patients with RA.
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alveolar bone loss is associated with circulating anti citrullinated Protein Antibody acpa in patients with rheumatoid arthritis
Journal of Periodontology, 2015Co-Authors: Shawneen M Gonzalez, Jeffrey B Payne, Geoffrey M Thiele, Alan R Erickson, Paul G Johnson, Marian J Schmid, Grant W Cannon, Gail S Kerr, Andreas M Reimold, Jeremy SokoloveAbstract:Background: This study examines: 1) alveolar bone loss (ABL), a hallmark of periodontitis, in anti-citrullinated Protein Antibody (ACPA)-positive rheumatoid arthritis (RA) patients versus control patients with osteoarthritis (OA); and 2) the association of ABL with RA disease activity and ACPA concentrations, including multiple antigen–specific ACPA.Methods: This multicenter case-control study includes 617 patients diagnosed with RA (n = 287) or OA (n = 330). Panoramic radiographs were taken; patients were categorized into low, moderate, or high tertiles based on mean percentage ABL. Serum ACPA was measured using second-generation anticyclic citrullinated peptide enzyme-linked immunosorbent assay and a multiplex platform to assess distinct antigen-specific ACPA. A generalized linear mixed model for binary data was used to compare stratified ABL in RA versus OA patients. Associations of moderate and high ABL (versus low) with RA disease activity and severity measures were examined using multivariate regres...
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rheumatoid factor as a potentiator of anti citrullinated Protein Antibody mediated inflammation in rheumatoid arthritis
Arthritis & Rheumatism, 2014Co-Authors: Jeremy Sokolove, Geoffrey M Thiele, Andreas M Reimold, Dannette S Johnson, Lauren J Lahey, Catriona A Wagner, Danye Cheng, Kaleb Michaud, Harlan Sayles, Liron CaplanAbstract:Objective The co-occurrence of rheumatoid factor (RF) and anti–citrullinated Protein Antibody (ACPA) positivity in rheumatoid arthritis (RA) is well described. However, the mechanisms underlying the potential interaction between these 2 distinct autoantibodies have not been well defined. The aim of this study was to evaluate the epidemiologic and molecular interaction of ACPAs and RF and its association with both disease activity and measures of RA-associated inflammation. Methods In a cohort of 1,488 US veterans with RA, measures of disease activity and serum levels of cytokines and multiplex ACPAs were compared between the following groups of patients: double-negative (anti–cyclic citrullinated peptide [anti-CCP]−/RF−), anti-CCP+/RF−, anti-CCP−/RF+, or double-positive (anti-CCP+/RF+). Additional studies were performed using an in vitro immune complex (IC) stimulation assay in which macrophages were incubated with ACPA ICs in the presence or absence of monoclonal IgM-RF, and tumor necrosis factor α production measured as a readout of macrophage activation. Results Compared with the double-negative subgroup (as well as each single-positive subgroup), the double-positive subgroup exhibited higher disease activity as well as higher levels of C-reactive Protein and inflammatory cytokines (all P < 0.001). In vitro stimulation of macrophages by ACPA ICs increased cytokine production, and the addition of monoclonal IgM-RF significantly increased macrophage tumor necrosis factor α production (P = 0.003 versus ACPA ICs alone). Conclusion The combined presence of ACPAs and IgM-RF mediates increased proinflammatory cytokine production in vitro and is associated with increased systemic inflammation and disease activity in RA. Our data suggest that IgM-RF enhances the capacity of ACPA ICs to stimulate macrophage cytokine production, thereby providing a mechanistic link by which RF enhances the pathogenicity of ACPA ICs in RA.
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porphyromonas gingivalis and disease related autoantibodies in individuals at increased risk of rheumatoid arthritis
Arthritis & Rheumatism, 2012Co-Authors: Ted R Mikuls, Jeffrey B Payne, Geoffrey M Thiele, Harlan Sayles, Kevin D Deane, James R Odell, Michael H Weisman, Peter K Gregersen, Jane H Buckner, Richard M KeatingAbstract:Objective. To examine the relationship of Porphyromonas gingivalis to the presence of autoantibodies in individuals at risk of rheumatoid arthritis (RA). Methods. Study participants included the following: 1) a cohort enriched in subjects with HLA–DR4 and 2) subjects at risk of RA by virtue of having a first-degree relative with RA. None of the study subjects satisfied the American College of Rheumatology 1987 classification criteria for RA. Autoantibodies measured included anti–citrullinated Protein Antibody (ACPA; by second-generation anti–cyclic citrullinated peptide
G Zeng - One of the best experts on this subject based on the ideXlab platform.
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effect of 32 67 kda laminin binding Protein Antibody on mouse embryo implantation
Reproduction, 2000Co-Authors: Chi Zhang, Enkui Duan, Yujing Cao, G Jiang, G ZengAbstract:Mouse embryo implantation depends on the complex interaction between the embryo trophoblast cells and the uterine environment, which deposits an extracellular matrix with abundant amounts of laminin. Intrauterine injection and blastocyst or ectoplacental cone culture models were used to study the effect of 32/67 kDa lamininbinding Protein Antibody on mouse embryo implantation in vivo and in vitro. Intrauterine injection of 32/67 kDa laminin-binding Protein Antibody (0.4 mg in 1 ml Ham’s F-10 medium, 5 μl per mouse) into the left uterine horns of mice (n = 22) on day 3 of pregnancy inhibited embryo implantation significantly (P < 0.001) compared with the contralateral horns that had been injected with normal rabbit IgG. A continuous section study on day 5 after injection showed that the embryos in the control uteri implanted normally and developed healthily, but there were no embryos or the remaining embryos had disintegrated in the uteri injected with 32/67 kDa lamininbinding Protein Antibody. Blastocysts or ectoplacental cones were cultured in media containing 32/67 kDa laminin-binding Protein Antibody (0.2 mg ml ‐1 ) on laminincoated dishes with normal rabbit IgG at the same concentration as in the controls. The 32/67 kDa laminin-binding Protein had no effect on blastocyst or ectoplacental cone attachment, but prohibited the blastocyst or ectoplacental cone outgrowth and primary or secondary trophoblast giant cell migration. These results indicate that 32/67 kDa laminin-binding Protein Antibody blocked mouse embryo implantation by preventing embryo trophoblast cell invasion and migration through the uterine decidual basement membrane-like extracellular matrix which has a high laminin content.
G Wolbink - One of the best experts on this subject based on the ideXlab platform.
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development of the anti citrullinated Protein Antibody repertoire prior to the onset of rheumatoid arthritis
Arthritis & Rheumatism, 2011Co-Authors: Lotte A Van De Stadt, G Wolbink, R J Van De Stadt, B A C Dijkmans, Margret H M T De Koning, Dorte Hamann, Dirkjan Van SchaardenburgAbstract:Objective. To examine how anti–citrullinated Protein Antibody (ACPA) epitope spreading takes place prior to the onset of clinical rheumatoid arthritis (RA), and to analyze the pattern of autoantigen reactivity at the beginning of the immune response. Methods. Multiple consecutive serum samples from 79 RA patients who had donated blood before disease onset were available for analysis. Fifty-three patients tested positive for ACPAs prior to the onset of clinical RA. For these patients, a median of 6 (interquartile range 4–9) sequential pre-RA serum samples obtained 1–2 years apart were tested. Reactivity to 5 distinct citrullinated peptides was measured by enzymelinked immunosorbent assay. Two peptides were derived from fibrinogen, 1 from vimentin, 1 from -enolase, and 1 from filaggrin. Results. In 25 of 53 ACPA-positive patients, seroconversion from ACPA absence to ACPA presence was observed. In 72% of these patients, the immune response started with reactivity to 1 peptide, without preference for a particular peptide. The number of peptides recognized increased over time, without a dominant epitopespreading pattern. ACPAs appeared in low levels several years prior to the diagnosis of RA. Antibody titers increased markedly 2–4 years before diagnosis. Conclusion. Our findings indicate that ACPA epitope spreading occurs over several years prior to the onset of clinical RA. The initial autoimmune response is mostly directed toward only 1 autoantigen, but this is not always the same antigen. The marked increase in ACPA titers a few years prior to the diagnosis of RA suggests a second stage in disease development, which might be due to a variety of factors.
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the extent of the anti citrullinated Protein Antibody repertoire is associated with arthritis development in patients with seropositive arthralgia
Annals of the Rheumatic Diseases, 2011Co-Authors: Lotte A Van De Stadt, Ger J M Pruijn, Wouter H Bos, G Wolbink, R J Van De Stadt, B A C Dijkmans, Ann R Van Der Horst, Margret H M T De Koning, Dirkjan Van Schaardenburg, Dorte HamannAbstract:Objectives To determine the fine specificity of anti-citrullinated Protein antibodies (ACPA) in the early phase of arthritis development, the ACPA repertoire in arthralgia patients and the association with arthritis development were studied. Methods A total of 244 patients with arthralgia positive for anti-cyclic citrullinated peptide antibodies (aCCPs) and/or IgM rheumatoid factor (IgM-RF), without arthritis were included. Development of arthritis was defined as presence of one or more swollen joints at clinical examination during follow-up. Sera were tested at baseline for reactivity to five citrullinated peptides derived from fibrinogen (three), vimentin (one) and α-enolase (one) and five corresponding arginine peptides in an ELISA. Results In all, 69 patients (28%) developed arthritis in a median of 3 joints after a median follow-up of 11 (IQR 5–20) months. Reactivity to each peptide was significantly associated with arthritis development (p Conclusions Arthritis development is not associated with recognition of a specific citrullinated peptide once joint complaints are present. The ACPA repertoire in some patients with arthralgia is expanded. High aCCP levels are associated with a qualitatively broad ACPA repertoire. Patients with an extended ACPA repertoire have a higher risk of developing arthritis.
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arthritis development in patients with arthralgia is strongly associated with anti citrullinated Protein Antibody status a prospective cohort study
Annals of the Rheumatic Diseases, 2010Co-Authors: Wouter H Bos, G Wolbink, M Boers, G J Tijhuis, N De Vries, I E Van Der Horstbruinsma, Paul P Tak, R J Van De Stadt, C J Van Der Laken, B A C DijkmansAbstract:Background Anti-citrullinated Protein antibodies (ACPA) are associated with increased risk for rheumatoid arthritis. Objective To investigate the effect of the presence and levels of ACPA on arthritis development in patients with arthralgia. Methods Patients with arthralgia positive for ACPA or IgM rheumatoid factor (IgM-RF) were tested for the shared epitope (SE) and were prospectively followed up for at least 12 months. Absence of clinical arthritis at inclusion and arthritis development during follow-up were independently confirmed by two investigators. Cox regression hazard analyses were used to calculate hazard ratios (HRs) for arthritis development. Results 147 patients with arthralgia were included (50 ACPA positive, 52 IgM-RF positive and 45 positive for both antibodies). After a median follow-up of 28 months (interquartile range (IQR) 19–39), 29 patients developed arthritis in a median of 4 (IQR 3–6) joints and 26 (90%) of these were ACPA positive. The presence of ACPA (HR = 6.0; 95% confidence interval (95% CI) 1.8 to 19.8; p = 0.004), but not of IgM-RF (HR = 1.4, 95% CI 0.6 to 3.1) nor the SE (HR = 1.5, 95% CI 0.7 to 3.0), was associated with arthritis development. Within the group of ACPA-positive patients, the risk for arthritis was enhanced by the presence of IgM-RF (HR = 3.0; 95% CI 1.4 to 6.9; p = 0.01) and high ACPA levels (HR = 1.7; 95% CI 1.1 to 2.5; p = 0.008), but not the SE (HR = 1.0; 95% CI 0.5 to 2.1; p = 1.0). Conclusion In patients with arthralgia the presence of ACPA (but not of IgM-RF or SE) predicts arthritis development. The risk in ACPA-positive patients may be further increased by the concomitant presence of IgM-RF or high levels of ACPA.
