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K Vos

Publications and source records attributed to K Vos.

At least 19 recordsLinked to original sources

Early and aggressive treatment of rheumatoid arthritis patients affects the association of HLA class II antigens with progression of joint damage.

OBJECTIVE: The presence of certain HLA class II antigens is strongly associated with the progression of joint destruction in rheumatoid arthritis (RA). Such antigens may be more effective than other class II antigens in inducing the formation of autoreactive T cells after presentation of (auto)antigens. We investigated whether early and aggressive treatment with disease-modifying antirheumatic drugs could modify this relationship. METHODS: We analyzed data from 2 studies of patients with early RA treated according to different strategies. The first study consisted of 2 cohorts, one (n = 109; median disease duration before treatment 4 months) was treated according to the pyramid strategy (initial nonsteroidal antiinflammatory drugs, followed by chloroquine [CQ] or sulfasalazine [SSZ] when necessary), and the other (n = 97; median disease duration before treatment 2 weeks) was immediately treated with CQ or SSZ. The second study comprised 155 patients (median disease duration 4 months) from the Combinatietherapie Bij Reumatoide Artritis (COBRA) trial, in which patients were randomly assigned to combination treatment with step-down prednisolone, methotrexate (MTX), and SSZ (n = 76) or with SSZ alone (n = 79). Prednisolone and MTX dosages were tapered and stopped after 28 and 40 weeks, respectively. The extent of joint damage was measured by the modified Sharp method. RESULTS: In the pyramid treatment cohort, the median increase in Sharp score after 2 years was 12 in patients positive for the shared epitope (SE) and 1 in SE- patients. In the immediate treatment cohort, the median increase was 3 in SE+ patients and 2 in SE- patients. In the SSZ group of the COBRA study, the median increase in Sharp score after 1 year was 11 in DR4+ patients and 3 in DR4- patients. In the combination treatment group, the median increase was 4 in DR4+ patients and 2 in DR4- patients. Significance was confirmed by multiple regression using log-transformed scores. CONCLUSION: Early and aggressive antirheumatic drug treatment affects the association of HLA class II alleles with progression of joint damage in RA.

Adult↗

Long-term outcome in rheumatoid arthritis: a simple algorithm of baseline parameters can predict radiographic damage, disability, and disease course at 12-year followup.

OBJECTIVES: To predict the long-term outcome of rheumatoid arthritis (RA) with respect to radiographic damage, disability, and disease course using baseline variables, and to construct decision trees identifying patients on an individual level at the extremes of the outcome spectrum of these 3 dimensions. METHODS: The 12-year outcome of 112 female RA patients from a prospective inception cohort was assessed by measuring the tertiles of radiographic damage (measured by the modified Sharp/van der Heijde method, SHS), disability (measured by the Health Assessment Questionnaire, HAQ), and severe disease course as defined by patients with either the 33% highest cumulative disease activity (area under the curve of all observed disease activity scores) or the highest tertile of radiographic damage. Patients in the lowest (mild) and highest tertile (severe) of each outcome measure were identified. All baseline parameters known to be associated with each outcome (demographic and socioeconomic parameters; disease duration; disease activity measures; laboratory measures including rheumatoid factor, HLA typing, percentage agalactosyl IgG, functional and radiographic measures) were entered into cross-validated stepwise logistic regression models to find the best predictive combination of baseline parameters for each of the outcomes. Using the results of the logistic regression models, simple decision trees were constructed to categorize patients at an individual level in a particular prognostic group. RESULTS: After 12 years, the lowest and highest tertiles were, respectively, 42.3 and 189 for the SHS and 0.37 and 1.25 for the HAQ. Fifty-five patients had a severe disease course. Mild and severe radiographic damage could be predicted with an accuracy of 90% and 85%, respectively. Mild and severe HAQ could be predicted with an accuracy of 90% and 84%, respectively, and severe disease course with an accuracy of 81%. The baseline variables found to be predictive of all 3 outcome measures were very similar and consisted of combinations of the following baseline parameters: swollen joint count (SJC), Ritchie score, rheumatoid factor (RF), the presence of erosions, and the HAQ score. Additional knowledge of the HLA typing hardly improved the accuracy of the prediction. To predict outcome at the individual level, simple decision trees were constructed using the RF, HAQ, SJC, and presence of erosions at baseline. CONCLUSION: The present study shows that prediction of outcome in long-term RA is possible and can be done using widely available baseline parameters.

Adult↗

Sarcoid arthritis: clinical characteristics, diagnostic aspects, and risk factors.

OBJECTIVES: (a) To describe the clinical characteristics of acute sarcoid arthritis and the diagnostic value of its presenting clinical features; (b) to evaluate whether disease onset is seasonal; and (c) to evaluate whether smoking behaviour or the presence of HLA class II alleles is a risk factor for the disease. METHODS: 579 consecutive patients with recent onset arthritis who had been newly referred to a rheumatology outpatient clinic were included in a prospective cohort study. The presenting clinical features, the smoking behaviour, and the results of HLA-DQ and HLA-DR DNA typing of 55 patients with sarcoid arthritis, 524 patients with other arthritides of recent onset, and samples of the normal population were compared. RESULTS: In all cases the disease showed a self limiting arthritis and overall good prognosis. The diagnostic ability of a combination of four clinical features--symmetrical ankle arthritis, symptoms of less than two months, age below 40 years, and erythema nodosum--was exceptionally high. When test positivity is defined as the presence of at least three of four criteria the set rendered a sensitivity of 93%, a specificity of 99%, a positive predictive value of 75%, and a negative predictive value of 99.7%. The disease clustered in the months March-July. The disease was negatively associated with smoking (odds ratio (OR) 0.09; 95% confidence interval (95% CI) 0.02 to 0.37) and positively associated with the presence of the DQ2 (DQB1*0201)-DR3 (DRB1*0301) haplotype (OR 12.33; 95% CI 5.97 to 25.48). CONCLUSION: The disease entity acute sarcoid arthritis has highly diagnostic clinical features. The seasonal clustering, the protective effect of smoking, and the association with specific HLA class II antigens support the hypothesis that it results from exposure of susceptible hosts to environmental agents through the lungs.

Adult↗

An HLA-DRB1-derived peptide associated with protection against rheumatoid arthritis is naturally processed by human APCs.

Predisposition to rheumatoid arthritis (RA) is thought to be associated with HLA-DR1, -DR4, and -DR10. However, many epidemiological observations are better explained by a model in which the DQ alleles that are linked to these DR alleles, i.e., DQ5, DQ7, and DQ8, predispose to RA, while certain DR alleles have a dominant protective effect. All protective DRB1 alleles, e.g., *0402, *1301, and *1302, encode a unique motif, (70)DERAA(74). The protection may be explained by the presentation of DRB1-derived peptides by DQ to immunoregulatory T cells, because it was demonstrated in various autoimmune disease models that T cell responses to certain self-Ags can be involved in disease suppression. The aim of this study was to analyze whether peptides carrying the DERAA motif are naturally processed by human APC and presented in the context of the RA-predisposing DQ. Using a synthetic peptide carrying the DRB1*0402-derived sequence (65)KDILEDERAAVDTYC(79), we generated DERAA peptide-specific DQ-restricted T cell clones (TCC) from a DQ8 homozygous individual carrying DERAA-negative DR4 alleles. By analyzing the proliferation of these TCC, we demonstrated natural processing and presentation of the DERAA sequence by the APC of all the individuals (n = 12) carrying a DERAA-positive DRB1 allele and either DQ8 or the DQ8-related DQ7. Using a panel of truncated synthetic peptides, we identified the sequence (67)(I)LEDERAAVD(TY)(78) as the minimal determinant for binding to DQ8 and for recognition by the TCC. These findings support a model in which self-MHC-derived peptide can modulate predisposition to autoimmune disease in humans.

Alleles↗

Human leukocyte antigen-DQ and DR polymorphisms predict rheumatoid arthritis outcome better than DR alone.

Conflicting data have been published on the value of the shared epitope (SE) hypothesis in predicting disease outcome in rheumatoid arthritis (RA). Recently we have proposed an alternative hypothesis, referred to as the RA protection (RAP) model. In this model, the HLA-DQ loci carry predisposition while HLA-DRB1 alleles encoding the motif DERAA provide protection against severe RA. In the present study, we have compared the respective values of the models in predicting both remission and erosions in early RA patients. We made use of an early arthritis clinic in which 158 RA patients and 138 patients with undifferentiated arthritis were enrolled. Patients were typed for HLA-DQ and -DR using high resolution DNA typing methods. Homozygosity for predisposing HLA-DQ alleles was associated with no remission and high erosion score. The presence of DERAA-bearing DRB1 alleles was negatively associated with erosions in otherwise predisposed individuals and increased the chance of being in remission. We found that the RAP model was significantly better than the SE model in predicting remission rate and erosion scores at one and two years in early RA patients. We conclude that HLA polymorphism does not only affect RA susceptibility, but also protects against severe disease at early stage.

Alleles↗

Evidence for a protective role of the human leukocyte antigen class II region in early rheumatoid arthritis.

OBJECTIVE: To analyse the distribution of predisposing DQ3 (DQB1*03(*04)/DQA1*03) and DQ5 (DQB1*0501/DQA1*01), shared epitope encoding and protective DRB1 alleles in patients with early rheumatoid arthritis (RA) and undifferentiated arthritis (UA). METHODS: Consecutive patients enrolled in an early arthritis clinic were DNA-typed for HLA-DQ and DR. RA patients (n=195), UA patients (n=160) and controls from the same region (n=306) were sorted according to their DQ-DR phenotypes: DQ3 vs DQ5 and the presence or absence of a protective DERAA-positive DRB1 molecule. The three groups were also sorted according to the shared epitope (SE) hypothesis. RESULTS: We observed the association of both DQ3 and DQ5 with RA. DQ3/3 homozygous individuals had the highest risk of developing disease [odds ratio (OR)=20.00]. Conversely DQ5, but not DQ3, was associated with undifferentiated arthritis (OR=2.15 vs 1.25). Consistent with these differences, DQ3-positive individuals had significantly more active disease at the first visit at the outpatient clinic than DQ5-positive patients. DRB1 alleles encoding a DERAA motif in their third hypervariable region provided a strong dominant protection against RA among DQ5-positive individuals and decreased arthritis activity among DQ3-positive patients. Individuals with SE-positive DR1, DR4 and DR10 alleles were also predisposed to RA, DR4/4 homozygous individuals having the highest risk of developing RA (OR=11.00). CONCLUSION: The DQ3-DR4/9 haplotypes are associated with RA. The DQ5-DR1/10 haplotypes are associated with less active disease, i.e. UA, and DERAA encoding DRB1 alleles modulate either predisposition to or the severity of RA. We propose that HLA polymorphism influences not only the initiation or perpetuation of RA but also protection against the disease.

Arthritis, Rheumatoid↗

Reduction of radiation exposure in the cardiac electrophysiology laboratory.

The purpose of this study was to determine the effects of various protective measures on patient and operator radiation dose levels in catheter ablation procedures. Catheter ablation procedures are associated with significant radiation levels. The patient's skin and operator radiation levels were measured (1) at baseline, (2) after primary beam filtration by 0.3-mm copper sheet and 2-mm aluminium plate and implementation of the LocaLisa system, and (3) after reduction of the left anterior oblique fluoroscopic pulse rate and installation of a lead glass screen. Additionally, a comparative analysis of radiation exposure levels was performed in the seven Dutch catheter ablation centers. Filtration of both primary beams resulted in a more than two-fold reduction in patient skin dose. Together with the LocaLisa system, this resulted in a six-fold reduction in patient and operator dose. As expected, lowering of the left anterior oblique pulse rate from 25 to 12.5 Hz reduced the corresponding patient skin dose with a factor 2 while the lead-glass protection caused an extra factor 2 reduction for the operator. Large differences were observed between fluoroscopy systems used for catheter ablation in the Netherlands. Depending on patient body mass and fluoroscopy system, patient skin dose varied between 0.2 and 8.4 Gy/hour. Proper measures may allow for a significant reduction of patient and operator radiation exposure in catheter ablation procedures. The large influence of body mass and equipment on patient's skin dose requires a more direct monitoring of skin dose than total fluoroscopy time.

Catheter Ablation↗

Cellular immune response to human cartilage glycoprotein-39 (HC gp-39)-derived peptides in rheumatoid arthritis and other inflammatory conditions.

OBJECTIVE: To study the specificity of the peripheral blood mononuclear cell (PBMC) response to peptides derived from human cartilage glycoprotein-39 (HC gp-39) in patients with rheumatoid arthritis (RA) and the correlation between this response and disease activity. METHODS: RA patients, patients with systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD) or osteoarthritis (OA) and healthy controls were studied. All individuals were typed for HLA-DRB1 and their disease activity score was documented. Proliferation of PBMC was measured following incubation with five different HC gp-39-derived peptides, selected by the use of a DR4 (DRB1*0401) binding motif. RESULTS: A proliferative response to one of the five peptides (peptide 259-271 at 10 microg/ml) was more often observed in RA patients than in healthy controls (P=0.001). RA patients who expressed DRB1*0401 more often showed a response against this peptide than RA patients who did not express this RA-associated haplotype. This response was not RA-specific since patients with IBD or OA also showed a response significantly more frequently than healthy controls (P:=0.02 and P=0.03 respectively). However, the level of the response against peptide 259-271 correlated with disease activity in RA patients but not in patients with IBD or SLE. Increased responses to HC gp-39 263-275 were found in patients with IBD or OA; a trend towards such a response failed to reach significance in RA patients in this study. CONCLUSION: In RA patients as well as in patients with other inflammatory conditions, HC gp-39-derived peptides may be targets of the T-cell-mediated immune response. In the RA patient group the immune response to HC gp-39-derived peptide 259-271 correlated with disease activity.

Adipokines↗

Raised human cartilage glycoprotein-39 plasma levels in patients with rheumatoid arthritis and other inflammatory conditions.

OBJECTIVE: To evaluate plasma human cartilage glycoprotein (HC gp-39) as a possible marker for the presence and/or activity of rheumatoid arthritis (RA) and other inflammatory conditions. BACKGROUND: HC gp-39 is a secretory product of chondrocytes, synovial cells, macrophages, and neutrophils. HC gp-39, also described as YKL-40, was found to be a marker of joint disease and tissue injury in RA and various other diseases. METHODS: Levels of HC gp-39 were determined by a sandwich enzyme linked immunosorbent assay (ELISA) in 47 patients with RA, 47 with osteoarthritis (OA), 24 with systemic lupus erythematosus (SLE), 24 with inflammatory bowel disease (IBD), and in 47 healthy controls. A disease activity score was assessed in the patients with RA, SLE, and IBD. RESULTS: The plasma level of HC gp-39 in the RA patient group was significantly higher than in the other patient groups and healthy controls. The level in patients with OA, SLE, and IBD was also significantly higher than the HC gp-39 level found in the healthy control group. HC gp-39 levels in patients with RA correlated positively with the ESR and IgM rheumatoid factor level but not with other variables of disease activity. In the patients with SLE and IBD no correlation was found with the disease activity score. CONCLUSION: The plasma level of HC gp-39 is increased in inflammatory conditions with and without joint disease (SLE, IBD, OA, and RA). Thus increased levels of HC gp-39 do not only reflect joint disease but also reflect inflammation or tissue degradation in various conditions. Notably, the highest level of HC gp-39 was found in patients with RA. Only in the RA patient group was a correlation between HC gp-39 plasma levels and some laboratory variables of disease activity found.

Adipokines↗

The clinical role of nuclear medicine in rheumatoid arthritis patients. A comparison with other diagnostic imaging modalities.

In patients with rheumatoid arthritis (RA) synovitis activity is the dominant clinical variable that determines the therapeutic approach. At present, the amount of painful and swollen joints assessed by physical examination, is generally used to measure the degree of synovitis activity. A gold standard for the assessment of synovitis activity is not available. The availability of an objective and reproducible method to evaluate synovitis activity in RA would be of great value in patient management and in examination of therapeutic effects. An advantage of the use of radiopharmaceuticals in detection of arthritis activity, compared with other imaging techniques, is the possibility to depict all joints in a single image. Furthermore the technique may image joints which are difficult to assess clinically or radiographically and may also detect joint inflammation in an early phase. In this overview different scintigraphic techniques are compared with each other and with other diagnostic imaging modalities.

Arthritis, Rheumatoid↗

Randomized trial of nurse-assisted strategies for smoking cessation in primary care.

BACKGROUND: Brief advice to stop smoking from general practitioners (GPs) has been repeatedly shown to increase smoking cessation by a small, but measurable amount. Some studies have suggested that adding more intensive interventions to brief advice may increase its effectiveness, but it is unclear whether this is true in general practice. AIMS: To determine whether brief advice from a doctor together with counselling and follow-up from a trained practice nurse is more effective than brief advice alone in helping people to stop smoking. METHODS: The design was a randomized controlled trial. Four hundred and ninety-seven general practice patients aged older than 18 years and smoking at least one cigarette per day in six general practices in Oxfordshire, Berkshire, and Buckinghamshire were randomized to one of two interventions: brief verbal or written advice from a GP plus extended counselling and follow-up from a trained practice nurse; brief advice from a GP alone. The primary outcome was sustained abstinence from smoking at three and 12 months. A secondary outcome was forward movement in the stages of change cycle. RESULTS: The proportion showing sustained abstinence was 3.6% in the extended counselling group, and 4.4% in the brief advice group (difference = -0.8%; 95% confidence interval = -4.3% to 2.6%). Seventy-four (30%) of those randomized to extended counselling actually took up this offer. No significant progression in stages of change was detected between the two groups. CONCLUSIONS: In unselected general practice patients who smoke, brief advice from a GP combined with intensive intervention and follow-up by a practice nurse is no more effective than brief advice alone.

Adolescent↗

Isolation of Borrelia burgdorferi from biopsy specimens taken from healthy-looking skin of patients with Lyme borreliosis.

Erythematous skin lesions due to infection with Borrelia burgdorferi will often disappear without antibiotic treatment. The aim of the study was to assess whether after disappearance of the erythematous skin lesion B. burgdorferi is still present in the healthy-looking skin of untreated patients. In six patients, a skin biopsy specimen was taken at the site of a previous erythematous skin lesion 1 to 6 months after disappearance of the lesion. Four of them presented with early disseminated Lyme borreliosis. In one additional patient with early disseminated Lyme borreliosis, the site of a previous tick bite was biopsied. None of these patients had been treated with antibiotics before presentation. The cultures of the skin biopsy specimens of the seven patients showed growth of Borrelia species. By rRNA gene restriction analysis and genospecies-specific PCR, six isolates were classified as Borrelia garinii and one as Borrelia group VS461. These results show that B. burgdorferi can still be cultured from the skin after disappearance of the erythematous skin lesion or at the site of a previous tick bite.

Adolescent↗

Seroconversion for Lyme borreliosis among Dutch military.

Few prospective studies for Lyme borreliosis (LB) have been conducted among subjects at risk to acquire this disease during their work when wearing well-defined protective clothing against tick-bites. We prospectively compared the rate of seroconversion and the occurrence of clinical manifestations of LB among 2 groups of Dutch military. The at risk-group worked predominantly outdoors, and the control-group conducted predominantly indoor activities. During outdoor work, the at risk-group wore long sleeves, long trousers, closed around the ankles and high boots. Initial serum samples from 2158 military were collected immediately after entering the service. From 932 military (at risk-group: 469, control-group: 463) a second sample was drawn 9 to 12 months later. Sera were tested for IgG and IgM antibodies by ELISA. Four persons (0.9%) in the at risk-group and 10 persons (2.2%) in the control-group seroconverted for IgG and/or IgM antibodies against B. burgdorferi. This difference was not statistically significant. Only 1 person who had seroconverted had noticed an erythema migrans. In conclusion, military performing outdoor activities have a low risk for infection with B. burgdorferi, most likely because they wear protective clothing. Among seroconverted persons clinical manifestations of Lyme borreliosis occurred rarely.

Adolescent↗

Different genospecies of Borrelia burgdorferi are associated with distinct clinical manifestations of Lyme borreliosis.

Borrelia burgdorferi sensu lato has been subdivided into three genospecies: B. burgdorferi sensu stricto, B. garinii, and B. burgdorferi group VS461. Sixty-eight isolates cultured from patients and 26 strains from ticks were characterized with use of SDS-PAGE, western blotting, and rRNA gene restriction analysis. Fifty-seven of 58 strains obtained from the skin of 70 patients who had erythema migrams or acrodermatitis chronica atrophicans were of group VS461, whereas the genotype of the remaining strain was unidentifiable. Of 10 strains cultured from CSF (n = 3) and skin (n = 7) of 20 patients with extracutaneous symptoms of Lyme borreliosis, nine were B. garinii and one was B. burgdorferi sensu stricto. Of these 20 patients, 17 had neuroborreliosis, one had arthritis and carditis, one had myalgia, and one had erythema and arthralgia. All 26 isolates from ticks were of group VS461. In conclusion, infections due to group VS461 and B. garinii are associated with cutaneous and extracutaneous symptoms, respectively. Our findings suggest that B. burgdorferi genotypes have different pathogenic potentials.

Acrodermatitis↗

Absence of Lyme borreliosis among patients with presumed Bell's palsy.

In a prospective study, 69 patients with a presumed idiopathic (Bell's) peripheral facial palsy were clinically and serologically evaluated for the presence of Lyme borreliosis. In addition, their clinical spectrum was compared with clinical manifestations collected retrospectively in nine patients with symptomatic peripheral facial palsy due to Lyme borreliosis. The seroprevalence of Borrelia burgdorferi antibodies, determined by flagellum enzyme-linked immunosorbent assay, among 69 patients with idiopathic peripheral facial palsy (6%) and 153 healthy controls (4.5%) was not significantly different (odds ratio, 1.28; 95% confidence interval, 0.27 to 5.25). None of the patients with idiopathic peripheral facial palsy had or experienced the development of Lyme borreliosis. All patients with Lyme peripheral facial palsy had additional manifestations not present in patients with idiopathic peripheral facial palsy. These findings show that patients with a Lyme peripheral facial palsy can be differentiated from patients with idiopathic peripheral facial palsy by clinical examination. Therefore, screening of antibodies to B burgdorferi among patients with idiopathic peripheral facial palsy without additional manifestations is not recommended.

Adolescent↗