Tom W J Huizinga

Leiden University Medical Centre, Leyden, South Holland, Netherlands

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Publications (489)3151.54 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: We recently demonstrated that MRI inflammation is prevalent in clinically non-swollen joints of early arthritis patients. In this study, we assessed the relevance of this subclinical inflammation with regard to radiographic progression.
    Annals of the rheumatic diseases. 07/2014;
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    ABSTRACT: Juvenile idiopathic arthritis (JIA) is considered a complex genetic autoimmune disease. We investigated the association of genetic variants previously implicated in JIA, autoimmunity and/or immunoregulation, with susceptibility to JIA.
    Annals of the rheumatic diseases. 07/2014;
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    ABSTRACT: Magnetic resonance imaging (MRI) is increasingly used in rheumatoid arthritis (RA) research. A European League Against Rheumatism (EULAR) task force recently suggested that MRI can improve the certainty of RA diagnosis. Because this recommendation may reflect a tendency to use MRI in daily practice, thorough studies on the value of MRI are required. Thus far no large studies have evaluated the accuracy of MRI to differentiate early RA from other patients with early arthritis. We performed a large cross-sectional study to determine whether patients who are clinically classified with RA differ in MRI features compared to patients with other diagnoses.
    The Journal of rheumatology. 07/2014;
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    ABSTRACT: Basophils are circulating granulocytes, best known as effector cells in allergic reactions. Recent studies in mice suggest that they might also participate in the suppression of chronic inflammation. The aim of this study was to assess the ability of purified human basophils to modulate monocyte responses upon IL-33 and IgE triggering.Activation of human basophils with IL-33 induced the production of IL-4 and the release of histamine, and enhanced their IgE-mediated activation. In addition, basophils triggered with IL-33 and anti-IgE significantly suppressed the LPS-induced production of the proinflammatory cytokine TNF-α and the upregulation of the co-stimulatory molecule CD80 by monocytes. These effects were mainly explained by the release of histamine, as they could be inhibited by the histamine receptor 2 antagonist ranitidine, with a smaller contribution of IL-4. In contrast, basophil-derived IL-4 and histamine had opposing effects on the expression of the inhibitory Fc γ receptor IIb and the production of IL-10 by monocytes. Our data show that basophils can influence monocyte activation and suggest a previously unrecognized role for human basophils in the modulation of monocyte-mediated immune responses, through the balanced secretion of histamine and IL-4.This article is protected by copyright. All rights reserved
    European Journal of Immunology 07/2014; · 4.97 Impact Factor
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    ABSTRACT: To translate and adapt the University of California, Los Angeles Scleroderma Clinical Trial Consortium Gastrointestinal Tract Instrument 2.0 (UCLA SCTC GIT 2.0) into Dutch and validate it among Dutch systemic sclerosis (SSc) patients.
    Clinical and experimental rheumatology 06/2014; · 2.66 Impact Factor
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    ABSTRACT: To determine whether T1 post-gadolinium chelate images (T1Gd) can replace T2-weighted images (T2) for evaluating bone marrow oedema (BME), thereby allowing a shorter magnetic resonance imaging (MRI) protocol in rheumatoid arthritis (RA).
    European radiology. 06/2014;
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    ABSTRACT: Mast cells may play a role in rheumatoid arthritis (RA), but activation of human mast cells in autoimmune settings has been little studied. Toll-like receptors (TLR) and Fcγ receptors (FcγR) are important receptors for cellular activation in the joint, but expression and stimulation of these receptors in human mast cells or the functional interplay between these pathways is poorly understood. Here, we analysed triggering of human mast cells via these receptors in the context of anti-citrullinated protein antibody-positive (ACPA+) RA. RNA and protein expression of TLRs and FcγR was quantified using PCR and flow cytometry, respectively. Mast cells were stimulated with TLR ligands (including HSP70) combined with IgG immune complexes and IgG-ACPA. Human mast cells expressed TLRs and produced cytokines in response to TLR ligands. Both cultured and synovial mast cells expressed FcγRIIA, and triggering of this receptor by IgG immune complexes synergised with activation by TLR ligands, leading to two- to fivefold increased cytokine levels. Mast cells produced cytokines in response to ACPA immune complexes in a citrulline-specific manner, which synergised in the presence of HSP70. Our data show that synovial mast cells express FcγRIIA and that mast cells can be activated by IgG-ACPA and TLR ligands. Importantly, combined stimulation via TLRs and immune complexes leads to synergy in cytokine production. These findings suggest mast cells are important targets for TLR ligands and immune complexes, and that combined activation of mast cells via these pathways greatly enhances inflammation in synovial tissue of RA patients.
    Annals of the rheumatic diseases 05/2014; · 8.11 Impact Factor
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    ABSTRACT: In rheumatoid arthritis (RA), several genetic risk factors and smoking are strongly associated with the presence of anticitrullinated protein antibodies (ACPA), while much less is known about risk factors for ACPA-negative RA. Antibodies against carbamylated proteins (anti-CarP) have been described in both ACPA-positive and ACPA-negative RA patients. In this study, we have analysed the relationships among anti-CarP antibodies, ACPA, genetic risk factors (HLA-DRB1 alleles and PTPN22) and smoking in RA. Presence of antibodies to carbamylated fetal calf serum (CarP-FCS) and fibrinogen (CarP-Fib) was determined by inhouse ELISAs among RA cases in the Leiden Early Arthritis Clinic (n=846) and in the Swedish Epidemiological Investigation of Rheumatoid Arthritis (n=1985) cohorts. ORs for associations with different HLA-DRB1 alleles, PTPN22 genotypes and smoking were calculated separately for each cohort as well as in meta-analysis in RA subsets defined by the presence/absence of anti-CarP and anticyclic citrullinated peptide (anti-CCP) antibodies. In both cohorts, anti-CarP antibody positivity was mainly detected in the anti-CCP-positive population (49%-73%), but also in the anti-CCP-negative population (8%-14%). No associations between anti-CarP antibodies and HLA-DRB1 shared epitope alleles could be identified, while there were data to support an association between anti-CarP-FCS and HLA-DRB1*03. Further analyses did not reveal any specific associations of anti-CarP antibodies with other HLA-DRB1 alleles, PTPN22 genotypes or smoking. Anti-CarP antibodies were present in both ACPA-positive and ACPA-negative RA. There were no significant associations among anti-CarP antibodies and HLA-DRB1 alleles, PTPN22 or smoking. These data suggest that different biological mechanisms may underlie anti-CarP versus anti-CCP antibody formation.
    Annals of the rheumatic diseases 05/2014; · 8.11 Impact Factor
  • Marieke Bax, Tom W J Huizinga, René E M Toes
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    ABSTRACT: Rheumatoid arthritis (RA) is an autoimmune disease affecting ∼1 % of the population. Although major advances have been made in the treatment of RA, relatively little is known about disease pathogenesis. Autoantibodies, present in approximately 60 % of the patients with early disease, might provide indications for immunological mechanisms underlying RA. Among the RA-associated autoantibodies, especially anti-citrullinated protein antibodies (ACPAs) have been studied intensively in the last decade. The discovery of ACPAs resulted into novel insight in RA pathogenesis and allowed division of the heterogeneous entity of RA into an ACPA-positive and ACPA-negative subset of disease. Other autoantibodies discovered in the serum of RA patients, including rheumatoid factors (RFs) targeting human IgG and anti-peptidylarginine deiminase (PAD)3/4 antibodies reactive against and activating the enzyme involved in citrullination, might contribute in collaboration with ACPAs to a feed-forward loop to aggravate erosive outcome of disease. Recently, a novel autoantibody system associated with RA was identified. These autoantibodies recognize carbamylated proteins (anti-CarP antibodies) and are detected in approximately 20 % of ACPA-negative patients, suggesting another parameter to sub-classify RA. In this review, the implication of autoantibodies in RA pathogenesis, diagnosis, prognosis and as biomarker for personalized medicine is discussed.
    Seminars in Immunopathology 04/2014; · 5.38 Impact Factor
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    ABSTRACT: In order to provide more patient-centered care for patients suffering from systemic lupus erythematosus (SLE), we studied their current satisfaction and preferences regarding future health care delivery. We sent questionnaires to all SLE patients visiting the rheumatology outpatient clinic in Leiden, the Netherlands. The questionnaire comprised three topics: (a) health care needs using a modified version of SLE Needs Questionnaire (range 0-38), (b) satisfaction with care per provider (visual analogue scale, range 0 (not at all)-100 (very satisfied)), and (c) preferences for future healthcare (four items). One hundred and two patients (63 % response) reported an average of 16 (±6) health care needs, with all patients reporting a need in the physical domain. More needs were significantly associated with worse physical functioning and a higher educational level. The average satisfaction score was 73 (±19) with a lower overall satisfaction score being associated with younger age and an educational level higher or lower than average. Regarding preferences for future health care delivery, 75 % of patients showed interest in a yearly standardized medical assessment, 57 % in regular, specialized nurse contacts using internet, 50 % in a yearly inventory on the need for self-management support, and 36 % in an education course. The association of age, education level and physical functioning with health care needs, and/or satisfaction suggest that the delivery of care should be better tailored to the needs of subgroups of patients.
    Clinical Rheumatology 04/2014; · 2.04 Impact Factor
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    ABSTRACT: The phase of arthralgia is the earliest moment to clinically recognize patients who may develop Rheumatoid Arthritis (RA). Previous imaging studies in the arthralgia phase have shown that inflammation precedes RA development. It is unknown which symptoms/characteristics relate to subclinical joint inflammation as measured by MRI. Among all patients with arthralgia, those with clinically suspect arthralgia (CSA) are suspected to progress to arthritis according to the clinical judgement of their rheumatologists. We determined the symptoms/characteristics of patients with CSA who had inflammation on MRI. 102 patients with CSA and without clinical arthritis were included. They completed questionnaires, underwent joint counts and unilateral 1.5 T MRI of MCP joints 2-4, wrist and MTP joints 1-5. Synovitis, bone marrow oedema (BME) and tenosynovitis were scored according to the OMERACT rheumatoid arthritis MRI scoring system. Symptoms and signs were related to MRI inflammation (based on MRI scores in symptom-free controls; a sum of synovitis, BME and tenosynovitis scores ≥3 was considered positive). Whether certain clinical characteristics frequently occurred together with MRI inflammation was studied by partial least squares analysis. MRI was performed in 93 patients with CSA, 44% of whom had subclinical MRI inflammation. Synovitis was the most prevalent inflammatory feature on MRI (20%). Patients with MRI inflammation were older and were more frequently positive for anti-citrullinated peptide antibodies than patients without MRI inflammation (p<0.001 and 0.049). In PLS analysis, including 16 clinical and serological characteristics as independent variables and MRI inflammation as dependent variable, no clear clusters of patients with and without MRI inflammation were identified. Subclinical inflammation as measured by MRI is present in 44% of patients with CSA. A combination of symptoms/characteristics incompletely differentiated patients with and without MRI inflammation.
    Annals of the rheumatic diseases 04/2014; · 8.11 Impact Factor
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    ABSTRACT: To investigate whether high molecular weight adiponectin (hmwAPN) mediates the associations of total adiponectin (totAPN) with radiographic progression in rheumatoid arthritis (RA) and hand osteoarthritis (HOA). Associations between baseline hmwAPN or totAPN levels with radiographic progression were determined using multivariate linear regression or generalized estimated equations. In patients with RA, totAPN associated positively, whereas in patients with HOA it associated negatively with radiographic progression. In contrast, hmwAPN did not associate significantly with radiographic progression in either cohort. Our data indicate that the differential effects associated between totAPN and radiographic progression in either RA or HOA are not mediated by hmwAPN.
    The Journal of Rheumatology 04/2014; · 3.26 Impact Factor
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    ABSTRACT: Despite progress in defining human leukocyte antigen (HLA) alleles for anti-citrullinated-protein-autoantibody-positive (ACPA(+)) rheumatoid arthritis (RA), identifying HLA alleles for ACPA-negative (ACPA(-)) RA has been challenging because of clinical heterogeneity within clinical cohorts. We imputed 8,961 classical HLA alleles, amino acids, and SNPs from Immunochip data in a discovery set of 2,406 ACPA(-) RA case and 13,930 control individuals. We developed a statistical approach to identify and adjust for clinical heterogeneity within ACPA(-) RA and observed independent associations for serine and leucine at position 11 in HLA-DRβ1 (p = 1.4 × 10(-13), odds ratio [OR] = 1.30) and for aspartate at position 9 in HLA-B (p = 2.7 × 10(-12), OR = 1.39) within the peptide binding grooves. These amino acid positions induced associations at HLA-DRB1(∗)03 (encoding serine at 11) and HLA-B(∗)08 (encoding aspartate at 9). We validated these findings in an independent set of 427 ACPA(-) case subjects, carefully phenotyped with a highly sensitive ACPA assay, and 1,691 control subjects (HLA-DRβ1 Ser11+Leu11: p = 5.8 × 10(-4), OR = 1.28; HLA-B Asp9: p = 2.6 × 10(-3), OR = 1.34). Although both amino acid sites drove risk of ACPA(+) and ACPA(-) disease, the effects of individual residues at HLA-DRβ1 position 11 were distinct (p < 2.9 × 10(-107)). We also identified an association with ACPA(+) RA at HLA-A position 77 (p = 2.7 × 10(-8), OR = 0.85) in 7,279 ACPA(+) RA case and 15,870 control subjects. These results contribute to mounting evidence that ACPA(+) and ACPA(-) RA are genetically distinct and potentially have separate autoantigens contributing to pathogenesis. We expect that our approach might have broad applications in analyzing clinical conditions with heterogeneity at both major histocompatibility complex (MHC) and non-MHC regions.
    The American Journal of Human Genetics 03/2014; · 11.20 Impact Factor
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    ABSTRACT: In rheumatoid arthritis (RA), smoking has been described to be specifically associated with the presence of anti-citrullinated protein antibodies (ACPA). However, smoking has also been shown to be associated with the presence of autoantibodies in various other autoimmune diseases, such anti-dsDNA in systemic lupus erythematosus and anti-Jo1 in idiopathic inflammatory myopathy. We therefore investigated whether smoking is specifically associated with ACPA-positive RA, or with autoantibody-positive RA in general. A meta-analysis was performed using RA patients from 5 countries: Norway, the Netherlands, Japan, Sweden, and the United Kingdom. Complete data on rheumatoid factor (RF)-, ACPA-status and tobacco exposure were available for 6320 RA patients. The odds ratios (ORs) and 95% confidence intervals (95% CIs) associated with the presence of RF, ACPA or both, were calculated by logistic regression comparing ever smokers with never smokers, and using the RF-negative ACPA-negative RA patients as the reference category. There was no significant association between smoking and RA in patients who were positive for only one antibody, being either RF (OR 1.04, 0.76 - 1.42) or ACPA (OR 1.00, 0.82 - 1.22). However, smoking was significantly associated with double-positive (RF-positive and ACPA-positive) RA (OR 1.55, 1.20 - 2.00). When ANA-status was also taken into account in the Dutch cohort, the association with smoking was strongest for the triple-positive group (OR = 2.43, 95% CI 1.47 - 4.00), although the difference with the double-positive RA patients (RF- and ACPA-positive, ANA-negative) (OR = 1.73, 95% CI 1.14 - 2.62) was not statistically significant. Smoking is not specifically associated with ACPA-positive RA, but rather with the concurrent presence of RF and ACPA in RA patients. These data indicate that smoking predisposes to the development of several autoantibodies, and that current hypotheses about the role of smoking in the pathophysiology of RA may need to be revisited.
    Annals of the rheumatic diseases 03/2014; 73 Suppl 1:A12. · 8.11 Impact Factor
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    ABSTRACT: In rheumatoid arthritis (RA), the presence of antibodies to citrullinated proteins (ACPA) is strongly associated with certain genetic risk factors and smoking. The recently identified antibodies against carbamylated proteins (anti-CarP) are present in part of ACPA-positive, but also ACPA-negative RA patients. This raised the question whether the presence of anti-CarP may be associated with specific risk factors, which could provide clues about the pathogenesis of ACPA-negative RA. In this study we have therefore analysed the relationship between anti-CarP antibodies, ACPA, genetic risk factors (HLA-DRB1 alleles and PTPN22) and smoking in RA. Presence of antibodies to carbamylated fetal calf serum (CarP-FCS) and fibrinogen (CarP-Fib) was determined by in-house ELISAs in the Leiden Early Arthritis Cohort (EAC) and in the Swedish Epidemiological Investigation of RA (EIRA) cohort. Odds ratios for associations with different HLA-DRB1 alleles, PTPN22 genotypes and smoking were calculated separately for each cohort as well as in a combined meta-analysis, in RA subsets defined by anti-CarP and anti-cyclic citrullinated peptide (CCP) antibody status. In both cohorts,anti-CarP antibodies were mainly detected in the anti-CCP-positive population, but also in the anti-CCP-negative population. No strong associations between anti-CarP antibodies and specific HLA-DRB1 alleles, including shared epitope alleles, could be identified, with the exception of a consistent association between anti-CarP FCS and HLA-DRB1*03. Further analyses did not reveal any specific associations between anti-CarP antibodies and PTPN22 genotypes or smoking. Anti-CarP antibodies were present in both ACPA-positive and ACPA-negative RA patients in the two separate cohorts. Except for a modest association with HLA-DRB1*03, there were no strong associations between anti-CarP antibodies and other HLA-DRB1 alleles, PTPN22 or smoking. Although it cannot be excluded that risk factors not investigated here may be importance for anti-CarP-positive disease, the lack of association found here suggests a possible fundamentally different biological mechanism for anti-CarP antibody formation compared with anti-CCP antibody formation.
    Annals of the rheumatic diseases 03/2014; 73 Suppl 1:A11-2. · 8.11 Impact Factor
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    ABSTRACT: Antibodies against citrullinated proteins are a characteristic of rheumatoid arthritis (RA). Recently, we demonstrated that autoantibodies recognizing homocitrulline containing proteins are present in sera of RA patients and predict joint damage (1). Because homocitrulline is post-translationally formed by a process called carbamylation, we named these novel auto-antibodies anti-Carbamylated Protein antibodies (anti-CarP antibodies). As no information is present on the molecular mechanisms underlying the break of tolerance and hence the induction of anti-CarP-responses, we analysed their appearance in the mouse collagen-induced arthritis (CIA) model. CIA was induced in mice by immunisation with type II collagen (CII) in complete Freund's adjuvant (CFA). Arthritis severity was monitored by clinical scoring and anti-CarP levels were determined by ELISA. The specificity of the ELISA was validated using inhibition and immunoblotting assays. Anti-CarP antibodies were not detected in naïve, non-immunised mice. However they were readily detectable in mice injected with CII and CFA demonstrating arthritic scores. The ELISA results of the specificity of the antibodies for carbamylated proteins were confirmed by inhibition assays and immunoblotting. No correlation between anti-CarP antibody levels and disease severity was observed. Injection of CFA could also cause the development of anti-Carp antibodies, indicating that arthritis is not required for the emergence of anti-CarP antibodies. However, in mice with arthritic disease, the anti-CarP response was stronger and developed more rapidly. The onset of clinical symptoms of CIA was preceded by an increase of anti-CarP IgG2a levels in the serum. Anti-CarP antibodies can be detected before disease onset in mice with CIA, but are not required for disease induction. Our data indicate that induction of inflammation by e.g. CFA can lead to a break of B-cell tolerance to carbamylated proteins and the emergence of anti-CarP-antibodies. This project is supported by Pfizer Inc. as part of the IMI BTCure program. L. A. T. receives a fellowship from Janssen Biologics BV (Johnson & Johnson). M. H. is a Pfizer Inc. employee. Shi J, et al. Autoantibodies recognizing carbamylated proteins are present in sera of patients with rheumatoid arthritis and predict joint damage. Proc. Natl. Acad. Sci. U. S. A 2011;108:17372-7.
    Annals of the rheumatic diseases 03/2014; 73 Suppl 1:A23-4. · 8.11 Impact Factor
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    ABSTRACT: Autoantibodies specific for citrullinated antigens are highly relevant diagnostic and prognostic biomarkers in rheumatoid arthritis and have been considered to be involved in disease pathogenesis. Previous studies have indicated that the ACPA-specific immune response differs from conventional B cell responses by generating polyclonal, cross-reactive antibodies of mostly low-avidity. In addition, ACPA were found to carry aberrant glycosylation patterns at the IgG-Fc tail. The present study was undertaken to further characterise the molecular make-up of ACPA and its potential functional consequences in the context of RA. Serum components of RA patients were fractionated by size exclusion chromatography and analysed for the presence of ACPA-IgG by ELISA. In addition, ACPA-IgG and non-citrulline-specific IgG were affinity purified from RA patient serum and synovial fluid and analysed by gel electrophoresis. Electrophoresis bands were excised and subsequently analysed by HPLC and mass-spectrometry. Recombinant monoclonal ACPA with variations in ACPA molecular structure were used to study binding affinity by surface plasmon resonance. We discovered that ACPA-IgG from RA patients have a higher apparent molecular weight as compared to other IgG molecules including antibodies against recall antigens and other autoantibodies. This higher molecular weight was explained by the overrepresentation of N-linked glycans in the variable domain (Fab region) of ACPA-IgG. Detailed structural analysis of these glycans demonstrated that ACPA-IgG linked Fab glycans are complex-type biantennary N-glycans that differ from the conventional Fc-linked N-glycans by a high degree of sialylation, galactosylation, and fucosylation together with the presence of bisecting N-acetylglucosamine. Using recombinant ACPA-IgG monoclonal antibodies with and without Fab-glycans, we found that Fab-glycans modulate binding affinity of ACPA-IgG for citrullinated antigens. Finally, lectin-immunoblotting showed that ACPA Fab-glycans can bind to sialic acid-binding immunoglobulin-type lectins. This study describes an unusual and novel molecular feature of the citrulline-specific immune response in RA. ACPA-IgG, in contrast to non-citrulline-specific IgG, are highly glycosylated in the variable region, which modulates recognition of citrullinated antigens. Moreover, ACPA-IgG linked Fab glycans can be the target of specific lectins, suggesting additional functional features potentially involved in ACPA-mediated pathogenetic effects. This finding points to aberrations in the development of ACPA-specific B cells and further elucidates our understanding of basic disease mechanisms in RA.
    Annals of the rheumatic diseases 03/2014; 73 Suppl 1:A19. · 8.11 Impact Factor
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    ABSTRACT: Anti-citrullinated protein antibodies (ACPA) and IgM-rheumatoid factor (IgM-RF) are auto-antibodies that can be detected many years before the clinical diagnosis of rheumatoid arthritis (RA). In recent studies we discovered a novel family of autoantibodies, anti-carbamylated protein (anti-CarP) antibodies. Carbamylation, like citrullination, is a post-translational modification of proteins. We observed that in RA, next to an antibody response against citrullinated proteins, also an immune response against carbamylated proteins exists. These anti-CarP antibodies are of prognostic value in RA as they associate with severe joint destruction in ACPA negative RA. In addition anti-CarP antibodies associate with future development of RA in patients suffering from arthralgia. Here we analysed whether anti-CarP antibodies are already present prior to symptom onset of RA and which auto-antibody appears first over time. Sera of 79 RA patients prior to diagnosis and 141 age and sex matched controls that were regular blood donors of the Amsterdam Bloodbank (Amsterdam, The Netherlands) were tested for the presence of anti-CarP antibodies, anti-CCP2 antibodies and RF-IgM using sequential pre-RA sera, obtained at 1-2 year intervals. Anti-CarP antibodies were present in 39% of the serum samples that were drawn just prior to the diagnosis of RA of blood donors compared to 4% of the matched control samples. Anti-CarP antibodies were present in both ACPA positive and in ACPA negative patients. Of the 79 individuals that developed RA, 42% were positive for anti-CCP2 antibodies and 24% for IgM RF. Analysis of the longitudinal samples revealed a gradual increase in the number of samples positive for anti-CarP antibodies and in the levels of anti-CarP antibodies towards the diagnosis of RA. We observed that anti-CarP antibodies could be detected many years before the onset of symptoms with a median of 8 years and a maximum of 14 years. Comparing the first appearance of the three autoantibody families revealed that both ACPA and anti-CarP antibodies appear earlier than IgM-RF. Next to ACPA and IgM-RF also the newly identified anti-CarP antibodies appear many years before the onset of clinical symptoms of RA.
    Annals of the rheumatic diseases 03/2014; 73 Suppl 1:A21. · 8.11 Impact Factor
  • Arthritis & rheumatology (Hoboken, N.J.). 02/2014;
  • I M Markusse, G Akdemir, T W J Huizinga, C F Allaart
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    ABSTRACT: Clinical trials have shown that in patients with long-standing low disease activity, tapering and/or stopping antirheumatic medication is a realistic option. The objective of this study is to explore patients' opinion about tapering and discontinuing antirheumatic drugs. This qualitative study is based on interviews with 20 patients with rheumatoid arthritis (RA) about RA treatment and treatment discontinuation through structured interviewing. Interviews were tape-recorded, transcribed verbatim, and screened by three assessors independently for meaning units. Not only positive emotions about drug discontinuation such as hope, happiness, and relief, but also fear and disappointment were mentioned. Some patients expect that drug discontinuation will be possible in other patients and/or themselves, while others do not expect this. The concept of increase in disease activity after discontinuing medication was mentioned, and while patients expect that disease activity will decrease again after restarting medication, they expect that this will take (too much) time. Positive emotions about the option to taper and discontinue antirheumatic medication, with negative expectations is a common combination in these RA patients. In particular, patients expect that disease activity will flare and that improvement upon restarting medication will take time. Patients' expectations and feelings should be addressed before drug tapering is attempted in a clear strategy of continued monitoring of disease activity.
    Clinical Rheumatology 01/2014; · 2.04 Impact Factor

Publication Stats

12k Citations
3,151.54 Total Impact Points


  • 2001–2014
    • Leiden University Medical Centre
      • Department of Rheumatology
      Leyden, South Holland, Netherlands
  • 2013
    • University of Leeds
      • Division of Rheumatic and Musculoskeletal Disease
      Leeds, ENG, United Kingdom
    • Harvard Medical School
      Boston, Massachusetts, United States
    • Bronovo Hospital
      's-Gravenhage, South Holland, Netherlands
    • GGD Zuid-Holland Zuid
      Dordt, South Holland, Netherlands
  • 2012
    • Maasstad Ziekenhuis
      Rotterdam, South Holland, Netherlands
  • 2011
    • The Bracton Centre, Oxleas NHS Trust
      Дартфорде, England, United Kingdom
  • 2010–2011
    • Karolinska Institutet
      • • Institutet för miljömedicin - IMM
      • • Institutionen för medicin, Huddinge
      Solna, Stockholm, Sweden
    • King's College London
      • Department of Academic Rheumatology
      London, ENG, United Kingdom
  • 2009–2010
    • Brigham and Women's Hospital
      • Division of Rheumatology, Immunology, and Allergy
      Boston, MA, United States
    • University Medical Center Utrecht
      Utrecht, Utrecht, Netherlands
    • Medical University of Vienna
      Wien, Vienna, Austria
  • 2008
    • Broad Institute of MIT and Harvard
      • Program in Medical and Population Genetics
      Cambridge, MA, United States
    • University of Coimbra
      Coímbra, Coimbra, Portugal
  • 2005–2008
    • VU University Medical Center
      • Department of Rheumatology
      Amsterdamo, North Holland, Netherlands
  • 2006
    • Revmatologicky Ustav
      Praha, Praha, Czech Republic
  • 2004
    • Ghent University
      • Rheumatology
      Gent, VLG, Belgium
    • Erasmus MC
      • Department of Obstetrics and Gynaecology
      Rotterdam, South Holland, Netherlands
  • 2003
    • Fundação Oswaldo Cruz
      • Laboratório de Hanseníase (IOC)
      Rio de Janeiro, Rio de Janeiro, Brazil
  • 2002
    • University of Glasgow
      Glasgow, Scotland, United Kingdom