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ABSTRACT: OBJECTIVE: The 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria for rheumatoid arthritis (RA) have been thoroughly studied for the test characteristics but it is unclear whether '2010 RA' has a different phenotype than '1987 RA' when assessing the severity of the disease course. Therefore this study compared two long-term disease outcomes. METHODS: 1502 early arthritis patients that had no other diagnoses than RA or undifferentiated arthritis (UA) were studied on fulfilling the 1987 ACR criteria, 2010 criteria or both. The severity of joint damage was studied with yearly radiographs over 7 years. Achieving disease-modifying anti-rheumatic drug (DMARD)-free sustained remission was assessed over 10-years follow-up. Multivariate normal regression and Cox-proportional hazard regression were used, adjusting for age, gender and treatment. RESULTS: 550 patients fulfilled the 1987 criteria, 788 patients the 2010 criteria and 489 both criteria sets. Patients fulfilling the 2010 criteria developed less severe radiological joint damage (p=0.023) and achieved DMARD-free sustained remission more often (HR=1.18 (0.93-1.50)) than patients fulfilling the 1987 criteria, though the latter was not statistically significant. All 1987+2010- patients were anti-citrullinated peptide antibody (ACPA)-negative. When also applying the radiologic criterion of the 2010-criteria, half of the 1987+2010- patients became 2010 criteria positive, but results on the long-term outcome remained similar. CONCLUSIONS: '2010 RA' has a milder disease course than '1987 RA'. This may have important implications for basic scientific studies and clinical trials in RA.
Annals of the rheumatic diseases 05/2013; · 8.11 Impact Factor
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ABSTRACT: OBJECTIVE: Hypercholesterolaemia, a risk factor for atherosclerosis (ATH), has been suggested to have a role in the development of osteoarthritis (OA). To test this hypothesis, the effect of cholesterol and different cholesterol-lowering treatments on OA was investigated in a mouse model resembling human lipoprotein metabolism. METHODS: Female ApolipoproteinE*3Leiden.human Cholesteryl Ester Transfer Protein mice received a western-type diet with 0.1% (w/w) cholesterol (LC), 0.3% (w/w) cholesterol alone (HC) or treated with 3 mg/kg/day atorvastatin or 0.3 mg/kg/day ezetimibe. One group remained on chow (control). After 39 weeks, OA grades of the knees and the extent of ATH were determined. Plasma cholesterol levels were measured throughout the study. RESULTS: LC and HC groups developed significantly more OA at the medial side than the control group in a dose-dependent manner. Atorvastatin but not ezetimibe treatment significantly suppressed OA development. As expected, features of ATH were significantly increased in the LC and HC groups compared with the control group and suppressed by atorvastatin (48%) and ezetimibe (55%) treatment. There were significant correlations between the development of OA on the medial side of the joint and cholesterol exposure (r=0.4) or ATH features (r=0.3). CONCLUSIONS: Dietary cholesterol and accordingly increased plasma levels play a role in the development of OA. The correlation found between OA, cholesterol and ATH demonstrates that these variables are connected, but indicates the contribution of other ongoing processes in the development of OA. The suppressive effect on OA development of atorvastatin but not of ezetimibe, which had similar cholesterol exposure levels, corroborates these findings.
Annals of the rheumatic diseases 04/2013; · 8.11 Impact Factor
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ABSTRACT: OBJECTIVE: Initiation of DMARD-therapy in the 'window of opportunity' is thought to result in a more effective modification of the processes underlying rheumatoid arthritis (RA). We questioned whether this effect is true or hyped and performed a systematic literature review. METHODS: Medical literature databases up to June 2012 were systematically reviewed for cohort studies and randomised controlled trials reporting outcome data of early RA in relation with symptom duration at treatment initiation. The quality of these studies was assessed by two independent reviewers using a criteria scoring system of 15 items. Studies were dichotomised with the median score (79%) as cut-off. Best-evidence synthesis was applied to determine the level of evidence per outcome category. A meta-analysis was performed on the studies reporting on achieving DMARD-free sustained remission (the reverse of disease persistency). RESULTS: Out of 836 screened articles, 18 fulfilled the selection criteria and were not duplicates. Ten were scored as high quality. Remission (various definitions) and radiographic progression were frequently studied outcomes. There was strong evidence for an association between symptom duration and radiographic progression. A meta-analysis on datasets evaluating DMARD-free sustained remission showed that symptom duration was independently associated with such remission; HR 0.989 (95% CI 0.983 to 0.995) per week increase in symptom duration. A moderate level of evidence was observed for other remission outcomes. CONCLUSIONS: Even when heterogeneity of patients is taken into account, prolonged symptom duration is associated with radiographic progression and a lower chance on DMARD-free sustained remission. These data may support the presence of a 'window of opportunity'.
Annals of the rheumatic diseases 04/2013; · 8.11 Impact Factor
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R Knevel,
D P C de Rooy,
A Zhernakova,
G Gröndal,
A Krabben,
K Steinsson,
C Wijmenga,
G Cavet,
R E M Toes, T W J Huizinga,
P K Gregersen,
A H M van der Helm-van Mil
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ABSTRACT: BACKGROUND: Heritability studies have suggested an important role of genetic predisposition ito progression of joint destruction in Rheumatoid Arthritis (RA); the heritability is estimated at 45-58%. Several SNPs have been identified to associate with RA susceptibility. We studied the association of several of these loci with progression of joint destruction. METHOD: In total 1,750 RA-patients with 4,732 Sharp-van der Heijde scored X-rays of four independent data-sets were studied. Thirteen susceptibility SNPs that were not associated with joint destruction before were tested in 596 Dutch RA-patients. Subsequently, significant SNPs were studied in RA data-sets from North-America and Iceland. Data were summarized in inverse weighted variance meta-analyses. Further, the association with circulating protein levels was studied and the associated region was fine-mapped. RESULTS: In stage-1, three loci (AFF3, IL2RA and BLK) were significantly associated with rate of joint destruction and were further analyzed in the additional data-sets. In the combined meta-analyses, the minor allele of IL2RA-rs2104286(C) was associated with less progression of joint destruction (P=7.2x10(-4) ). Furthermore, the IL2RA-rs2104286 protective genotype was associated with lower circulating levels of soluble IL-2RA (0.85 95%CI 0.77-0.93, P=1.4x10(-3) ). Additionally, lower sIL-2RA levels were associated with a lower rate of joint destruction (P=4.2x10(-3) ). The association of IL2RA with rate of joint destruction was further focused to a region of 40kb encompassing the IL2RA intron 1 and the 5' region of IL2RA and RBM17. CONCLUSION: Present genetic and serologic data suggest that inherited altered genetic constitution at IL2RA locus may predispose to a less destructive course of RA. © 2013 American College of Rheumatology.
Arthritis & Rheumatism 03/2013; · 7.87 Impact Factor
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R Knevel,
A Krabben,
A G Wilson,
E Brouwer,
M K Leijsma,
E Lindqvist,
D P C de Rooy,
N A Daha,
M P M van der Linden,
S Tsonaka,
A Zhernakova,
H-J Westra,
L Franke,
J J Houwing-Duistermaat,
R E M Toes, T W J Huizinga,
T Saxne,
A H M van der Helm-van Mil
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ABSTRACT: Genetic factors account for an estimated 45-58% of the variance in joint destruction in rheumatoid arthritis (RA). The serine proteinase granzyme B induces target cell apoptosis, and several in vitro studies suggest that granzyme B is involved in apoptosis of chondrocytes. Serum levels of granzyme B are increased in RA and are also associated with radiographic erosions. The aim of this study was to investigate GZMB as a candidate gene accounting for the severity of joint destruction in RA.
A total of 1,418 patients with 4,885 radiograph sets of the hands and feet from 4 independent cohorts were studied. First, explorative analyses were performed in 600 RA patients in the Leiden Early Arthritis Clinic cohort. Fifteen single-nucleotide polymorphisms (SNPs) tagging GZMB were tested. Significantly associated SNPs were genotyped in data sets representing patients from the Groningen, Sheffield, and Lund cohorts. In each data set, the relative increase in the annual rate of progression in the presence of a genotype was assessed. Data were summarized in a meta-analysis. The association of GZMB with the RNA expression level of the GZMB genomic region was tested by mapping expression quantitative trait loci (QTLs) on 1,469 whole blood samples.
SNP rs8192916 was significantly associated with the rate of joint destruction in the first cohort and in the meta-analysis of all data sets. Patients homozygous for the minor allele of rs8192916 had a higher rate of joint destruction per year compared with other patients (P = 7.8 × 10(-4) ). Expression QTL of GZMB identified higher expression in the presence of the minor allele of rs8192916 (P = 2.27 × 10(-5) ).
SNP rs8192916 located in GZMB is associated with the progression of joint destruction in RA as well as with RNA expression in whole blood.
Arthritis & Rheumatism 03/2013; 65(3):582-9. · 7.87 Impact Factor
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ABSTRACT: OBJECTIVE: To assess the association between high body mass index (BMI) and treatment response in recent onset RA. METHODS: In the BeSt study, 508 patients were randomized to initial monotherapy or combination therapy with prednisone or infliximab (IFX). Response to disease activity score (DAS)≤2.4 steered treatment (first dose and after 1 year) was compared between patients with a BMI <25 and ≥25, using relative risk regression analyses. DAS, components of DAS and functional ability during the first year were compared using linear mixed models. RESULTS: High BMI was independently associated with failure to achieve DAS≤2.4 on initial therapy, RR 1.20 (1.05-1.37). The effect for combination therapy with prednisone was RR 1.55 (1.06-2.28) and for combination therapy with IFX 1.42 (0.98-2.06). The RRs for failure after one year were 1.46 (0.75-2.83) and 2.20 (0.99-4.92) respectively. High BMI was also associated with failure on delayed combination therapy with IFX, after adjustment for selection bias related to previous failure on DMARDs. No significant association was observed in the initial monotherapy groups. In the first year, patients with a high BMI had higher DAS and worse functional ability, with more tender joints and a higher VAS global health, but not more swollen joints and similar systemic inflammation. CONCLUSIONS: High BMI was independently associated with failure to achieve low DAS on initial combination therapy with prednisone and on initial and delayed treatment with infliximab. Patients with a high BMI experienced more pain, but not more swelling or systemic inflammation. © 2013 by the American College of Rheumatology.
Arthritis care & research. 02/2013;
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ABSTRACT: OBJECTIVE: Although a few consistent osteoarthritis (OA) susceptibility genes have been identified, little is known on OA progression. Since OA progression is clinically the most relevant phenotype, we investigate the association between ASPN, BMP5 and GDF5 polymorphisms and progression of hand OA. METHODS: Single-nucleotide polymorphisms (SNPs) ASPN rs13301537, BMP5 rs373444 and GDF5 rs143383 were genotyped in 251 hand OA patients from the Genetics osteoARthritis and Progression (GARP) study and 725 controls. In a case-control comparison we assessed the association between these SNPs and radiographic progression of hand OA over six years, which was based on change in osteophytes or joint space narrowing (JSN), above the smallest detectable change. SNPs with suggestive evidence for association were further analysed for their effect on progression over two years, and for the mean change in osteophytes and JSN. RESULTS: The minor allele of ASPN SNP rs13301537 was associated with hand OA progression over six years (OR (95%CI) 1.49 (1.06, 2.07); p=0.020). The mean change in osteophytes and JSN was higher in carriers of the minor allele compared to homozygous carriers of the common allele with mean difference of 0.73 (95%CI -0.07, 1.56; p=0.073) and 0.82 (95%CI 0.12, 1.52; p=0.022), respectively. An association with similar effect size was found between ASPN SNP rs13301537 and two-year progression, and the mean change in osteophytes and JSN was significantly higher in homozygotes. CONCLUSION: ASPN is associated with hand OA progression. This gives insight in the pathogenesis of hand OA progression and identified a potential target for therapeutic approaches.
Osteoarthritis and Cartilage 01/2013; · 3.90 Impact Factor
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ABSTRACT: Prosthetic joint infection (PJI) is a major complication after total joint arthroplasty. The most common source of these PJIs is a wound infection immediately after implantation of the artificial joint; however, haematogenous infection is also a common source of PJIs. We describe 3 patients, all suffering from (rheumatoid) arthritis, who presented at the emergency department with a wound on the foot or ankle and a swollen and painful prosthetic knee joint, which was functioning well for a long period of time (6 months to 5 years). All patients had several debridements of their infected total knee arthroplasty with local and systemic antibiotics. Patient outcome was widely diverse: from death to successful treatment. These case descriptions are good examples of the different outcomes from a major complication after a small wound. Care should be taken particularly for wounds around the foot and ankle in patients with a total joint arthroplasty, especially those who also have diabetes, rheumatoid arthritis or are immunocompromised.
Nederlands tijdschrift voor geneeskunde 01/2013; 157(12):A5448.
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ABSTRACT: OBJECTIVE: To determine incidence of increased levels of alanine transferase (ALT) >2× upper limit of normal (ULN) in patients receiving methotrexate (MTX), treated according to a dynamic strategy, and to identify predictors of ALT of >2× ULN. METHODS: Data of 508 recent-onset rheumatoid arthritis (RA) patients from the BeSt study, randomized to initial monotherapy or combination therapy, were used. Treatment was dynamic, aiming at a disease activity score = ≤ 2.4. ALT was measured every three months. With logistic regression analyses, baseline variables predictive of first ALT of >2× ULN were identified and the association between use of concomitant antirheumatic drugs, the actual and cumulative dose of MTX and ALT of >2× ULN was determined. RESULTS: In total, 498 patients ever initiated MTX, with a total duration on MTX of 1,416 patient-years. In 89 patients, a first incidence of ALT of >2× ULN occurred. Incidence rate was 6.3 per 100 patient-years and cumulative incidence 18 %. ACPA positivity and baseline ALT of >1× ULN were independent predictors of later ALT of >2× ULN (OR 1.8 (95 % CI, 1.1-3.1) and OR 3.1 (95 % CI, 1.6-6.2), respectively). Smoking showed a trend (OR 1.6 (95 % CI, 0.98-2.7)). Mean MTX dosage over time was higher in patients with an ALT of >2× ULN. Patients who did not have an ALT of >2× ULN used more concomitant disease-modifying antirheumatic drugs and longer. CONCLUSIONS: In RA patients treated with MTX according to a dynamic strategy resembling daily clinical practice, incidence of increased ALT of >2× ULN was lower than previously reported, and also without treatment adjustments, persistence was rare. The recommendations for ALT monitoring may be reevaluated.
Clinical Rheumatology 12/2012; · 2.00 Impact Factor
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ABSTRACT: Rheumatoid arthritis (RA) is a common autoimmune disease affecting around 1% of the population. Although major advances have been made in the treatment of RA, still relatively little is known on disease pathogenesis and aetiology. From treatment studies it has become clear that treating patients early in their disease course will provide the best results. However, especially in the early phase of arthritis, in particular when the patients do not yet fulfil the criteria for RA, it is difficult to decide which patients would benefit most from an early and aggressive intervention. Good biomarkers are important to guide decisions in the clinical management of RA. Next to the well-known rheumatoid factor (RF) and the anti-citrullinated protein antibodies (ACPA), several new markers are now likely to become available with interesting potential. Besides antibody responses directed against citrullinated proteins, also antibodies against carbamylated proteins (anti-CarP) have recently been shown to be present in RA. Interestingly these anti-CarP antibodies are also present in around 20% of the ACPA-negative RA patients and are associated with more severe joint damage in this group. Apart from the antibodies that help in establishing the diagnosis and prognosis, also novel biomarkers that reflect clinical disease activity scores are being discovered. The development of biomarker-based disease activity scores might allow easy and frequent monitoring of patients to rapidly adjust treatment.
The Netherlands Journal of Medicine 11/2012; 70(9):392-9. · 2.07 Impact Factor
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ABSTRACT: OBJECTIVE: To assess risk factors for progression of hand osteoarthritis (OA). METHODS: In a systematic review of cohort studies, medical literature databases were searched up to May 2012 for articles reporting data on the association between risk factors and hand OA progression. The quality of these studies was assessed by two independent reviewers using a criteria scoring system of 16 items, and studies were dichotomized in those with scores over or under ò69%. Best-evidence synthesis was used to determine the level of evidence per risk factor. RESULTS: Fourteen articles were included that fulfilled the selection criteria, of which eight were of high quality. The most frequently investigated risk factors were age, sex, radiographic features (e.g. erosive OA) and scintigraphy. Progression was mostly defined on radiographic criteria, but also clinical progression as outcome was described. Most investigated factors showed limited or inconclusive evidence for the association with hand OA progression. Limited evidence according to the best-evidence synthesis with most available studies was present for the association between a positive scintigraphic scan and radiographic progression (up to 2.8 times more progression than negative joints). CONCLUSION: Limited evidence is available for a positive association between an abnormal scintigraphic scans and radiographic hand OA progression. These data suggest that a positive scintigraphy as inclusion criteria for studies that aim to show structural modification can increase the power of such studies. Future longitudinal studies with a well-defined baseline population are needed to search for risk factors of hand OA progression. © 2012 by the American College of Rheumatology.
Arthritis care & research. 09/2012;
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ABSTRACT: Although osteoarthritis (OA) is considered a non-inflammatory condition, it is widely accepted that synovial inflammation is a feature of OA. However, the role of immune cells and their cytokines in OA is largely unknown. This narrative systematic review summarizes the knowledge of inflammatory properties, immune cells and their cytokines in synovial tissues (STs) of OA patients.
Broad literature search in different databases was performed which resulted in 100 articles.
Of 100 articles 33 solely investigated inflammation in OA ST with or without comparison with normal samples; the remaining primarily focussed on rheumatoid arthritis (RA) ST. Studies investigating different severity stages or cellular source of cytokines were sparse. OA ST displayed mild/moderate grade inflammation when investigated by means of haematoxylin and eosin (H&E) staining. Most frequently found cells types were macrophages, T cells and mast cells (MCs). Overall the number of cells was lower than in RA, although the number of MCs was as high as or sometimes even higher than in RA ST. Cytokines related to T cell or macrophage function were found in OA ST. Their expression was overall higher than in normal ST, but lower than in RA ST. Their cellular source remains largely unknown in OA ST.
Inflammation is common in OA ST and characterized by immune cell infiltration and cytokine secretion. This inflammation seems quantitatively and qualitatively different from inflammation in RA. Further research is needed to clarify the role of inflammation, immune cells and their cytokines in the pathogenesis of OA.
Osteoarthritis and Cartilage 09/2012; 20(12):1484-99. · 3.90 Impact Factor
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Annals of the rheumatic diseases 07/2012; · 8.11 Impact Factor
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ABSTRACT: OBJECTIVE: To evaluate the contribution of joint space narrowing (JSN) and erosions in general and in four different joint groups in relation to physical disability in rheumatoid arthritis (RA). METHODS: 5-year follow-up data from the Behandel Strategieën (BeSt) trial were used, where 508 patients with recent onset RA were treated aiming at a disease activity score ≤2.4. Joint damage was assessed annually and scored according to the Sharp-van der Heijde method. Physical disability was measured 3-monthly with the Health Assessment Questionnaire (HAQ). Generalised Estimating Equations analyses were performed to assess the relationship between the HAQ and JSN scores and erosions scores, separately and in joint groups. RESULTS: Overall, damage scores were low, and neither total JSN nor erosions showed a significant effect on HAQ (β=0.001 95% CI -0.003 to 0.004 and β=0.002 95% CI -0.001 to 0.006, respectively). Of the total damage scores per joint group, damage in the wrist shows a trend for association with physical disability displaying the largest effect size (β=0.005 95% CI 0.000 to 0.011). Also in the analysis with erosions per joint group, the wrist was most strongly related with physical functioning (β=0.016 95% CI 0.003 to 0.029); in the analysis with JSN per joint group no joint group was significantly related to the HAQ. Analysis of all erosion and narrowing scores per joint group in one model reveals only erosions in the wrist to be independently associated with impaired physical functioning (β=0.017 95% CI 0.003 to 0.030). CONCLUSIONS: Joint damage in the wrist, erosions more than JSN, is associated with impaired physical functioning even in patients with early RA with limited overall damage after 5 years tightly controlled treatment.
Annals of the rheumatic diseases 06/2012; · 8.11 Impact Factor
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ABSTRACT: Rheumatoid arthritis (RA) is diagnosed based on phenotypic characteristics. The 2010 ACR/EULAR criteria were derived with the aim of classifying RA earlier in the disease course than the 1987 ACR criteria. When reviewing thus far published validation studies, it is clear that the 2010 criteria can be fulfilled earlier in time than the 1987 criteria. Therefore, the taskforce that derived the 2010 criteria has succeeded in their main objective. Furthermore, it has been repeatedly shown that the sensitivity of the 2010 criteria is increased compared with the 1987 criteria, but the specificity decreased. As classification criteria aim to arrive at homogeneous groups of patients in order to compare the results of clinical or experimental studies, this decrease in specificity is of concern, as patients with diagnoses other than RA can test positive on the criteria. With regard to diagnosing RA, the overall trend in the data is that early arthritis patients in the rheumatological setting who fulfil the 2010 criteria have a high probability of the disease. Not fulfilling the criteria, in contrast, does not rule out RA in these individuals.
Annals of the rheumatic diseases 05/2012; 71(10):1596-8. · 8.11 Impact Factor
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Journal of Neurology 04/2012; 247(1):63-64. · 3.47 Impact Factor
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ABSTRACT: Several prediction models for rapid radiological progression (RRP) in the first year of rheumatoid arthritis have been designed to aid rheumatologists in their choice of initial treatment. The association was assessed between RRP and disability and joint damage progression in 8 years.
Patients from the BeSt cohort were used. RRP was defined as an increase of ≥5 points in the Sharp/van der Heijde score (SHS) in year 1. Functional ability over 8 years, measured with the health assessment questionnaire (HAQ), was compared for patients with and without RRP using linear mixed models. Joint damage progression from years 1 to 8 was compared using logistic regression analyses.
RRP was observed in 102/465 patients. Over 8 years, patients with RRP had worse functional ability: difference in HAQ score 0.21 (0.14 after adjustment for disease activity score (over time)). RRP was associated with joint damage progression ≥25 points in SHS in years 1-8: OR 4.6.
RRP in year 1 is a predictor of worse functional ability over 8 years, independent of baseline joint damage and disease activity. Patients with RRP have more joint damage progression in subsequent years. RRP is thus a relevant outcome on which to base the initial treatment decision.
Annals of the rheumatic diseases 04/2012; 71(9):1530-3. · 8.11 Impact Factor
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R Knevel,
A Krabben,
E Brouwer,
M D Posthumus,
A G Wilson,
E Lindqvist,
T Saxne,
D de Rooy,
N Daha,
M P M van der Linden,
G Stoeken,
L van Toorn,
B Koeleman,
R Tsonaka,
A Zhernakoza,
J J Houwing-Duistermaat,
R Toes, T W J Huizinga,
A van der Helm-van Mil
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ABSTRACT: Interleukin (IL)-15 levels are increased in serum, synovium and bone marrow of patients with rheumatoid arthritis (RA). IL-15 influences both the innate and the adaptive immune response; its major role is activation and proliferation of T cells. There are also emerging data that IL-15 affects osteoclastogenesis. The authors investigated the association of genetic variants in IL15 with the rate of joint destruction in RA.
1418 patients with 4885 x-ray sets of both hands and feet of four independent data sets were studied. First, explorative analyses were performed on 600 patients with early RA enrolled in the Leiden Early Arthritis Clinic. Twenty-five single-nucleotide polymorphisms (SNPs) tagging IL-15 were tested. Second, SNPs with significant associations in the explorative phase were genotyped in data sets from Groningen, Sheffield and Lund. In each data set, the relative increase of the progression rate per year in the presence of a genotype was assessed. Subsequently, data were summarised in an inverse weighting meta-analysis.
Five SNPs were significantly associated with rate of joint destruction in phase 1 and typed in the other data sets. Patients homozygous for rs7667746, rs7665842, rs2322182, rs6821171 and rs4371699 had respectively 0.94-, 1.04-, 1.09-, 1.09- and 1.09-fold rate of joint destruction compared to other patients (p=4.0×10(-6), p=3.8×10(-4), p=5.0×10(-3), p=5.0×10(-3) and p=9.4×10(-3)).
Independent replication was not obtained, possibly due to insufficient power. Meta-analyses of all data sets combined resulted in significant results for four SNPs (rs7667746, p<0.001; rs7665842, p<0.001; rs4371699, p=0.01; rs6821171, p=0.01). These SNPs were also significant after correction for multiple testing.
Genetic variants in IL-15 are associated with progression of joint destruction in RA.
Annals of the rheumatic diseases 03/2012; 71(10):1651-7. · 8.11 Impact Factor
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P Suwannalai,
L A van de Stadt,
H Radner,
G Steiner,
H S El-Gabalawy,
C M Jol-van der Zijde,
M J van Tol,
D van Schaardenburg, T W J Huizinga,
R E M Toes,
L A Trouw
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ABSTRACT: Anti-citrullinated protein antibodies (ACPAs) are highly specific for rheumatoid arthritis (RA) and are present years before the onset of symptoms. The avidity of autoantibodies can have a strong impact on their effector potency. This study was undertaken to analyze the avidity of ACPAs in serum samples obtained from ACPA-positive healthy individuals (predisease), patients with early disease, and patients with established RA as well as the avidity maturation over time in samples from healthy subjects who later developed RA.
We measured ACPA avidity in serum samples from ACPA-positive healthy individuals, symptomatic individuals, and patients with established RA in 5 collections from The Netherlands, Canada, and Austria. We determined the dynamics of avidity maturation of ACPAs from the predisease stage to established disease in 1 case from the native North American population and in 10 cases from a Dutch blood donor cohort.
The overall ACPA response was characterized by low-avidity antibodies. Higher-avidity ACPAs were observed in symptomatic patients only, while low-avidity ACPAs were observed in both healthy subjects and patients. In longitudinal samples obtained from subjects prior to disease onset, ACPA avidity increased over time until disease onset. No further avidity maturation was observed after disease onset.
Our findings indicate that avidity maturation of the ACPA response takes place prior to disease onset.
Arthritis & Rheumatism 11/2011; 64(5):1323-8. · 7.87 Impact Factor
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Annals of the rheumatic diseases 11/2011; 71(4):627-8. · 8.11 Impact Factor
