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Biomedical subjects

T W J Huizinga

Publications and source records attributed to T W J Huizinga.

At least 19 recordsLinked to original sources
PubMed2007

Ex vivo interleukin 1 receptor antagonist production on lipopolysaccharide stimulation is associated with rheumatoid arthritis and with joint damage.

OBJECTIVES: (1) To assess innate ex vivo production of interleukin 1beta (IL1beta) and interleukin 1 receptor antagonist (IL1Ra) in patients with recent-onset rheumatoid arthritis (RA) as compared with healthy controls; (2) to assess the association of ex vivo IL1beta and IL1Ra production with progression of joint damage in RA; (3) to determine whether differences in ex vivo IL1beta production are explained by distribution of the IL1beta single nucleotide polymorphism C-511T. METHODS: Levels of IL1beta and IL1Ra (measured by ELISA after whole-blood stimulation with lipopolysaccharide) and distribution of IL1beta C-511T were compared in 76 patients with recent-onset RA who had received no disease-modifying antirheumatic drugs (DMARDs), and 63 healthy controls. ORs for RA based on ex vivo IL1beta and IL1Ra production were calculated. Association of ex vivo IL1beta and IL1Ra production with progression of joint damage (Sharp-van der Heijde score over 2 years) was determined by linear regression with correction for baseline characteristics. RESULTS: Patients with recent-onset RA showed lower ex vivo IL1beta and higher ex vivo IL1Ra production than healthy controls (p<0.001), with ORs for RA of 2.4 (95% CI 1.2 to 4.9) for low IL1beta-producers and 7.6 (95% CI 3.2 to 18.0) for high IL1Ra-producers. High ex vivo IL1Ra production was associated with progression of joint damage (p = 0.01). The IL1beta C-511T genotype distribution was not significantly different between patients and controls. CONCLUSIONS: Patients with recent-onset RA had decreased ex vivo IL1beta production and increased ex vivo IL1Ra production compared with controls. Ex vivo IL1Ra production is an independent predictor of progression of joint damage in recent-onset RA.

Acute Disease↗
PubMed2006

FCRL3 promoter 169 CC homozygosity is associated with susceptibility to rheumatoid arthritis in Dutch Caucasians.

BACKGROUND: Human leucocyte antigen is the only genetic risk factor for rheumatoid arthritis (RA) that has been consistently observed in different populations. A number of other genes such as PTPN22 and PADI4 showed population-specific association with RA susceptibility. Recently, Fc receptor-like 3 (FCRL3) gene was found to be associated with RA susceptibility in Japanese, but with conflicting results in other populations. OBJECTIVE: To investigate the association of FCRL3 polymorphism with RA susceptibility and severity in Dutch Caucasian patients with RA, as well as to perform a meta-analysis to reveal the contribution of this gene to RA susceptibility. METHODS: A total of 931 Dutch RA cases and 570 unrelated Dutch controls were genotyped for four FCRL3 single-nucleotide polymorphisms (SNPs). Genotyping was performed using the MassArray matrix-assisted laser desorption ionisation-time-of-flight mass spectrometry. Association of the FCRL3 SNPs with susceptibility to RA was examined by single-marker, carrier and haplotype analysis. RESULTS: Carrier analysis of the SNP (rs7528684) revealed the association of CC genotype with a higher risk of developing RA as compared with TT and TC carriers (p = 0.039 and OR = 1.31). There was no significant difference in the genotype and allele frequencies of all investigated SNPs between cases and controls. Meta-analysis of all studies comparing 9467 individuals showed that the OR for the CC genotype to develop RA was 1.2 and the p value <0.001. CONCLUSION: A promoter polymorphism of FCRL3 (rs7528684) is associated with an increased risk of developing RA in Dutch Caucasians, suggesting that this association is relevant for RA in both Japanese and Caucasian populations.

Adult↗
PubMed2006

Arthritis of the large joints - in particular, the knee - at first presentation is predictive for a high level of radiological destruction of the small joints in rheumatoid arthritis.

OBJECTIVE: To investigate the predictive value of the distribution of inflamed joints at first presentation for the severity of the disease course in rheumatoid arthritis (RA). METHODS: Of the 1009 consecutive patients included in the Leiden Early Arthritis Clinic (Leiden, The Netherlands), 285 patients fulfilled the American College of Rheumatology criteria for RA within 1 year of follow-up. Of these, 28 patients achieved remission. Radiographs of hands and feet were scored according to the Sharp-van der Heijde method, and the 28 patients with the most destructive disease were selected. The distribution of inflamed joints of the patients with the extreme disease courses was compared. The association between the distribution of inflamed joints and the level of destruction of the joints of hands and feet in the whole group of patients with RA was assessed using regression analysis. RESULTS: Comparison of patients with extreme disease courses using univariate and logistic regression analyses showed that arthritis of the large joints - in particular, the knee - was associated with severe RA. In the whole group of patients with RA, the total number of swollen joints and the presence of knee arthritis were associated independently with the level of destruction of the small joints. Patients with RA with knee arthritis had higher C reactive protein (CRP) levels than patients without knee arthritis, and investigating the distribution of inflamed joints together with other variables yielded the number of swollen joints, CRP, presence of anti-cyclic citrullinated peptide antibodies and symptom duration as predictors for severity of RA. CONCLUSION: Arthritis of large joints - in particular, the knee - at first presentation is associated with a destructive course of RA.

Aged↗
PubMed2006

The 620W allele is the PTPN22 genetic variant conferring susceptibility to RA in a Dutch population.

OBJECTIVES: A missense SNP, C1858T, in PTPN22 has been identified as a genetic risk factor for rheumatoid arthritis (RA). Subsequent work has suggested that other variants in this gene, in particular a haplotype marked by the minor allele of rs3789604, are associated with RA in white North Americans independent of C1858T. We tested this hypothesis in an independent white Dutch study. METHODS: A total of 667 RA patients and 286 controls were genotyped for 13 PTPN22 single nucleotide polymorphisms (SNPs) by allele-specific kinetic polymerase chain reaction. rs3789604 was genotyped in an additional 410 RA and 270 UA patients participating in the Leiden early arthritis inception cohort. We conducted single-marker and haplotype association tests. RESULTS: The sole haplotype strongly associated with RA in our Dutch population carries the PTPN22 1858T allele. A second haplotype identical at all other SNPs tested except 1858 was not associated with disease. No significant association of the haplotype tagged by the 3' PTPN22 SNP, rs3789604, with RA susceptibility (P = 0.134) was observed in our sample set. CONCLUSION: We conclude that C1858T is the sole PTPN22 variant predisposing to RA in our white Dutch sample set.

Adult↗
PubMed2006

Interleukin 10: a new risk marker for the development of restenosis after percutaneous coronary intervention.

Genetic factors appear to be important in the process of restenosis after percutaneous coronary intervention (PCI), as well as in inflammation, a pivotal factor in restenosis. An important mediator in the inflammatory response is interleukin (IL)-10. Our aim was to study whether genetic variants in IL-10 predispose to the risk of restenosis. The GENetic DEterminants of Restenosis (GENDER) study included 3104 patients treated with successful PCI. Target vessel revascularization (TVR) was chosen as primary end point. Genotyping of the -2849G/A, -1082G/A, -592C/A and +4259A/G polymorphisms of the IL-10 gene was performed by MassArray platform. After adjusting for clinical variables, three polymorphisms significantly increased the risk of restenosis (-2849AA: relative risk (RR), 1.7, 95% confidence interval (CI), 1.2-2.5; -1082AA: RR, 1.4, 95% CI, 1.1-1.8 and +4259GG: RR, 2.0, 95% CI, 1.4-2.8). To further exclude possible involvement of neighboring genes due to LD in the IL-10 locus, additional polymorphisms were genotyped. The results reveal that association of the IL-10 gene with restenosis is independent of flanking genes. Our findings demonstrate that IL-10 is associated with restenosis and therefore support the hypothesis that anti-inflammatory genes also may be involved in developing restenosis. Furthermore, they may provide a new targeting gene for drug-eluting stents.

3' Untranslated Regions↗
PubMed2006

Interleukin-10 promoter polymorphisms in male and female fertility and fecundity.

Interleukin-10 (IL10) is assumed beneficial for a successful pregnancy; it may increase fertility and fecundity. Allele frequencies of IL10 polymorphisms at position -2849, -1082 and -592 were analyzed in association with a past history of fertility and fecundity in men and women of at least 85 years old. Fertility was decreased in association with the -2849 A allele in females; 27% of the AA genotype carriers produced no offspring in marriage compared to 14% of the G allele carriers (odds ratio (OR): 2.2, 95% confidence interval (CI): 1.2-4.2, P=0.01). Effective fecundability was decreased in association with the -2849 A allele in females; 7% of female -2849 AA genotype carriers had a child within 371 days of marriage (therefore, conceived within 3 months of marriage) compared to 28% of female G allele carriers (OR: 0.2, 95% CI: 0.04-0.7, P=0.01). This suggests an association between the -2849 AA genotype and a decreased fertility and fecundity in females.

Aged, 80 and over↗
PubMed2006

How evidence-based are advertisements in journals regarding the subspecialty of rheumatology?

OBJECTIVES: In rheumatology, five different billion-dollar drugs have emerged in recent years, making this subspecialty the focus of extensive advertising campaigns. Considering this development and the fact that the scientific content of advertisements has been questioned, we initiated a study to determine how evidence-based advertisements are in four leading journals of rheumatology. METHODS: Advertisements were extracted from the journals Arthritis and Rheumatism, Rheumatology, Seminars in Arthritis and Rheumatism and the Journal of Rheumatology, and were evaluated using a standardized score form. RESULTS: In total, 353 advertisements were obtained, of which 84 were unique. Of the 300 references provided by these unique advertisements, 53 (18%) were considered 'supporting'. In addition, 87 (29%) of the 300 references referred to randomized controlled trials (RCTs), of which 49% supported the claim. The vast majority of RCTs (97%) were sponsored by the advertising company. In the 84 unique advertisements 288 claims were made, of which 190 provided one or more references. Of these 190 claims, 33 (17%) were judged 'well supported'. In total, only four (5%) of the 84 different advertisements were judged 'well supported' and 11 (13%) of the 84 were judged 'misleading' because they contained one or more misleading claims, i.e. claims with references to articles contradicting the claim. CONCLUSIONS: This study indicates that few advertisements in rheumatology journals are entirely evidence-based.

Advertising↗
PubMed2006

[Neurological or psychiatric symptoms in patients with systemic lupus erythematosus (SLE): terminological problems, pathogenesis, diagnosis and therapy].

The nomenclature of the American College of Rheumatology leads to misunderstandings in multidisciplinary discussions on patients with systemic lupus erythematosus (SLE) who also have neurological or psychiatric symptoms. These proposed neuropsychiatric syndromes are rarely syndromes and the symptoms are rarely neuropsychiatric. It is better first of all to determine whether the SLE patients have neurological or psychiatric symptoms, and if these symptoms are present, the first question is what is the cause. Vasculitis of the cerebral blood vessels should be considered as a possible explanation only if ischaemic lesions in the brain have been demonstrated, other causes of cerebral ischaemia in SLE are unlikely, and the clinical signs are consistent with cerebral vasculitis. These other causes of cerebral ischaemia include: antiphospholipid antibodies, atherosclerosis, heart valve disorders and thrombotic thrombocytopenic purpura.

Brain↗
PubMed2006

Isotype distribution of anti-cyclic citrullinated peptide antibodies in undifferentiated arthritis and rheumatoid arthritis reflects an ongoing immune response.

OBJECTIVE: The evolution of the rheumatoid arthritis (RA)-specific anti-cyclic citrullinated peptide (anti-CCP) antibody response, as measured by the isotypes of anti-CCP, has not been described. This study was undertaken to determine anti-CCP isotype usage in patients with undifferentiated arthritis (UA), patients with recent-onset RA, and patients with RA of long duration. METHODS: IgA, IgM, and IgG subclasses of anti-CCP were measured by enzyme-linked immunosorbent assay in serum samples that were obtained from IgG anti-CCP antibody-positive patients with UA (n = 110) and IgG anti-CCP antibody-positive patients with RA (n = 152) early after the onset of arthritis. Patients with UA in whom RA developed within 1 year (UA-->RA) were compared with patients with UA in whom RA did not develop within 1 year (UA-->UA). In addition, baseline serum samples obtained from a subset of patients with RA (n = 64) were compared with sera obtained from the same patients a median of 7 years later. RESULTS: IgM anti-CCP was present in early samples from both patients with UA and patients with RA and in followup samples from patients with RA. Several IgG anti-CCP antibody-positive patients who did not have IgM anti-CCP early after disease onset did display IgM anti-CCP later in the course of the arthritis. A diverse pattern of isotype usage was detected in early samples, with a trend toward lower frequencies of all isotypes of anti-CCP in patients with UA compared with patients with RA and in UA-->UA patients compared with UA-->RA patients. Levels of all isotypes except IgG1 had decreased after 7 years. CONCLUSION: These data indicate development of the anti-CCP isotype repertoire into full usage early in the course of arthritis. The sustained presence of IgM anti-CCP indicates ongoing recruitment of new B cells into the anti-CCP response, reflecting a continuous (re)activation of the RA-specific anti-CCP response during the course of anti-CCP-positive arthritis.

Antibody Formation↗
PubMed2005

Smoking is a risk factor for anti-CCP antibodies only in rheumatoid arthritis patients who carry HLA-DRB1 shared epitope alleles.

OBJECTIVES: To study the gene-environment interaction of tobacco exposure and shared epitope on autoantibodies in patients with rheumatoid arthritis and undifferentiated arthritis. METHODS: From incident cases of arthritis (n = 1305), patients who did not fulfil any classification criteria (undifferentiated arthritis (n = 486)) and those who fulfilled the American College of Rheumatology criteria for rheumatoid arthritis (n = 407) were identified. IgM rheumatoid factor (RF), anti-cyclic-citrullinated peptide (CCP) antibodies, and HLA-DRB1 alleles were determined. RESULTS: In rheumatoid arthritis, an interaction was found between tobacco exposure and shared epitope for the presence of anti-CCP antibodies, as the odds ratio for anti-CCP antibodies in patients having both tobacco exposure (TE) and shared epitope (SE) was higher than the summed odds ratios of patients having only tobacco exposure or shared epitope (odds ratios: TE+/SE-, 1.07; TE-/SE+, 2.49; and TE+/SE+, 5.27-all relative to TE-/SE-). A similar effect was found for RF, but stratification showed that the interaction primarily associated with the anti-CCP antibody response. In patients with undifferentiated arthritis at two weeks, or with persistent undifferentiated arthritis after one year, no interaction between tobacco exposure and shared epitope was observed for the presence of autoantibodies. CONCLUSIONS: Tobacco exposure increases the risk factor for anti-CCP antibodies only in shared epitope positive patients with rheumatoid arthritis. The gene-environment interaction between smoking and shared epitope leading to autoantibodies is specific for rheumatoid arthritis and is not observed in undifferentiated arthritis.

Aged↗
PubMed2005

Comparison of long term outcome of patients with rheumatoid arthritis presenting with undifferentiated arthritis or with rheumatoid arthritis: an observational cohort study.

BACKGROUND: The outcome of undifferentiated arthritis (UA) ranges from remission to rheumatoid arthritis (RA) fulfilling the American College of Rheumatology (ACR) classification criteria. OBJECTIVES: To report the outcome of UA after 1 year of follow up and compare the disease course of patients who presented with UA, but evolved into RA within 1 year (UA-RA group), with that of patients who presented with RA fulfilling the ACR criteria (RA-RA group). METHODS: The diagnosis of 330 patients who presented with UA was recorded at 1 year. The UA-RA and RA-RA groups were then followed up for 3 more years. Outcome measurements were radiographic progression, disease activity, and functional capacity. RESULTS: From 330 patients who were diagnosed UA, 91 had evolved into RA at 1 year; 62 patients had presented with RA. No significant differences were detected between the UA-RA and RA-RA groups in median Sharp/van der Heijde score at baseline, radiographic progression rates, disease activity, and functional capacity. However, significantly more disease modifying antirheumatic drugs were prescribed in the RA-RA group. CONCLUSION: The disease outcome of patients who present with UA that evolves into RA within 1 year is the same as that of patients who present with RA as measured by radiographic progression, disease activity, and functional capacity.

Adult↗
PubMed2005

A comparison of the diagnostic accuracy and prognostic value of the first and second anti-cyclic citrullinated peptides (CCP1 and CCP2) autoantibody tests for rheumatoid arthritis.

OBJECTIVES: To compare the diagnostic performance and prognostic value of the anti-cyclic citrullinated peptide (CCP1) and anti-CCP2 autoantibody tests in a clinical setting. METHODS: Anti-CCP1 and anti-CCP2 antibody tests were performed on the same serum samples obtained from 467 patients with early arthritis from the Leiden Arthritis Cohort. The sensitivity, specificity, positive predictive value, and negative predictive value for discriminating between rheumatoid arthritis (RA) and non-RA at 1 year's follow up were calculated for both tests. Results were graphically presented using receiver operating characteristic curves. Progression of radiological joint damage was assessed over 4 years in patients with RA and used to assess the prognostics values of the CCP tests. RESULTS: At a similar specificity the CCP2 test had a higher sensitivity than the CCP1 test. Both tests identified a subgroup of patients with RA with an increased rate of joint damage progression. The anti-CCP2 test identified more patients with an increased rate of joint damage progression than the anti-CCP1 test, and in multiple regression analysis CCP2 was the better predictor of joint damage. CONCLUSIONS: The CCP2 test had better diagnostic and prognostic ability than the CCP1 test.

Adolescent↗
PubMed2005

MMP protein and activity levels in synovial fluid from patients with joint injury, inflammatory arthritis, and osteoarthritis.

OBJECTIVE: To determine protein and activity levels of matrix metalloproteinases 1 and 3 (MMP-1 and MMP-3) in synovial fluid of patients with knee joint injury, primary osteoarthritis, and acute pyrophosphate arthritis (pseudogout). METHODS: Measurements were done on knee synovial fluid obtained in a cross sectional study of cases of injury (n = 283), osteoarthritis (n = 105), and pseudogout (n = 65), and in healthy controls (n = 35). Activity of MMP-1 and MMP-3 in alpha(2) macroglobulin complexes was measured using specific low molecular weight fluorogenic substrates. ProMMP-1, proMMP-3, and TIMP-1 (tissue inhibitor of metalloproteinase 1) were quantified by immunoassay. RESULTS: Mean levels of proMMP-1, proMMP-3, and TIMP-1 were increased in injury, osteoarthritis, and pseudogout compared with controls. MMP-1 activity was increased in pseudogout and injury groups over control levels, whereas MMP-3 activity was increased only in the pseudogout group. The increase in MMP-1 activity coincided with a decrease in TIMP-1 levels in the injury group. CONCLUSIONS: Patients with joint injury have a persistent increase in proMMP-1 and proMMP-3 in synovial fluid and an increase in activated MMPs, which are not inhibited by TIMP. The differences in activation and inhibition patterns between the study groups are consistent with disease specific patterns of MMP activation and/or inhibition in joint pathology.

Acute Disease↗
PubMed2005

Clinical efficacy of infliximab plus methotrexate in DMARD naive and DMARD refractory rheumatoid arthritis is associated with decreased synovial expression of TNF alpha and IL18 but not CXCL12.

BACKGROUND: Tumour necrosis alpha (TNF alpha) blocking agents lead to pronounced clinical effects and reduced synovial infiltrate in rheumatoid arthritis. Laboratory and clinical studies suggest that TNF alpha independent pathways play a role in the disease. OBJECTIVES: To evaluate the immunopathological effects of combination therapy on rheumatoid synovial tissue in order to identify TNF alpha independent mechanisms. METHODS: 12 rheumatoid patients, including four DMARD (disease modifying antirheumatic drug) naive patients with early disease, were studied for the effect of combination therapy with infliximab and methotrexate on the synovial infiltrate. Biopsies and clinical assessments (DAS28) were carried out before the first and after the third infusion of infliximab. Synovial inflammation was scored semiquantitatively. Co-expression of CD38(+) cells was studied by an immunofluorescent double labelling technique. RESULTS: Marked clinical responses were associated with a global reduction in the synovial infiltrate and expression of cytokines, notably interleukin 18 and TNF alpha, but low grade disease activity persisted. There was no effect on the expression of CXC chemokine ligand (CXCL12), and germinal centre-like structures were still detectable in synovial tissue in two patients after treatment. CD38(+) activated T cells were more resistant to treatment than CD38(+) plasma cells. No differences in clinical response or effects on synovial infiltrate were observed between DMARD refractory and DMARD naive patients. CONCLUSIONS: Persistent expression of CXCL12 and incomplete resolution of lymphocytic infiltrates after infliximab plus methotrexate indicates that TNF alpha independent mechanisms are operative in rheumatoid arthritis. This may contribute to low grade disease activity, even in DMARD naive patients with early disease.

Adult↗