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ABSTRACT: Treatment of rheumatic diseases, such as rheumatoid arthritis, systemic lupus erythematosus and Bechterew's disease is still improving and the number of fertile patients with a wish to conceive will probably increase. New knowledge regarding the course of rheumatic diseases during pregnancy and post partum herald a change in the support of women with rheumatic diseases who desire to have children. Justified use of antirheumatic drugs before, during and after pregnancy is a key issue for a successful pregnancy. The newer agents such as tumour necrosis factor (TNF) alpha blocking agents can also be of use. Specific preconception care should be offered to women with rheumatic diseases to optimize and increase chances of a successful pregnancy.
Nederlands tijdschrift voor geneeskunde 01/2011; 155(13):A2622.
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ABSTRACT: Both Th1 cells and Th17 cells have been recognized in rheumatoid arthritis (RA); however, it remains unclear whether Th1 cells and/or Th17 cells are involved in driving disease chronicity and destructiveness. The aim of this study was to identify and characterize the functional role of Th17 cells in early RA.
Flow cytometry analysis was performed on peripheral blood mononuclear cells (PBMCs) from treatment-naive patients with early RA and age-matched healthy volunteers. PBMCs from these patients, naive T cells, and primary CCR6- Th1 cells and CCR6+ Th17 cells were sorted and cultured in the absence or presence of synovial fibroblasts from patients with early RA (RASFs), and cytokine expression and gene transcription were analyzed. In addition, tumor necrosis factor α (TNFα)- and interleukin-17A (IL-17A)-blocking experiments were performed.
In the PBMCs of treatment-naive patients with early RA, an increased fraction of IL-17A-and TNFα-producing CCR6+ Th17 cells was observed. When cocultured with RASFs, these primary Th17 cells were potent inducers of IL-6 and IL-8 and the tissue-destructive enzymes matrix metalloproteinase 1 (MMP-1) and MMP-3, whereas primary Th1 cells or naive T cells were not. Importantly, specific up-regulation of IL-17A but not TNFα or interferon-γ was observed in RASF/Th17 cell cocultures. In addition to TNFα blocking, IL-17A neutralization was required to further down-regulate Th17 activity in RASF/Th17 cell cocultures.
Th17 cells, but not Th1 cells, cooperated with RASFs in a proinflammatory feedback loop, revealing a potential mechanism by which human Th17 cells drive chronic destructive disease in patients with RA. Furthermore, the neutralization of IL-17A activity is essential in current anti-TNF therapies to suppress Th17 cell activity in patients with early RA and potentially other Th17 cell-mediated disorders.
Arthritis & Rheumatism 10/2010; 63(1):73-83. · 7.87 Impact Factor
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ABSTRACT: In RA, conflicting results have been described on the association between genotypes of the complement factor mannose-binding lectin (MBL) and disease susceptibility and severity. This might be due to underpowerment of previous research work and the fact that no confirmation cohorts were used. Therefore a different approach is warranted.
MBL2 gene polymorphisms were determined in two RA cohorts (378 and 261 cases) and 648 controls. Considering MBL polymorphisms, cases and controls were categorized in groups of high, intermediate and low MBL production. The total sample size allows detection of a potential association between RA susceptibility and MBL groups with an odds ratio of 1.37 (alpha < 0.05; 1-beta > 0.8). Disease severity as defined by the need for anti-TNF therapy was also analysed for possible associations with MBL groups.
There was no difference in the frequencies between MBL genotypes of RA cases and controls that are associated with high (cases 54.4%, controls 57.0%), intermediate (cases 28.9%, controls 27.5%) or low (cases 16.7%, controls 15.5%) MBL production. Furthermore, there was no association between MBL groups and disease severity.
MBL genotype groups are not associated with RA disease susceptibility or severity in this large study including a confirmation cohort. Compared with previous smaller studies these results add to more definite conclusions.
Rheumatology (Oxford, England) 08/2008; 47(8):1168-71. · 4.24 Impact Factor
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ABSTRACT: The complement factor mannose-binding lectin (MBL) is associated with adverse pregnancy outcome. MBL serum concentrations are increased from early pregnancy onwards and depend upon several gene polymorphisms. We investigated whether MBL polymorphisms are associated with term and preterm birth, since preterm birth is the leading cause of neonatal morbidity and mortality.
MBL2 gene polymorphisms were determined in 157 nulliparous women. Considering MBL polymorphisms cases were categorized in groups of high (A), intermediate (B) and low (C) MBL production. Kaplan-Meier survival and multiple linear regression analysis were performed.
Women with high MBL genotype group A had a shorter gestational age (274 days+/-S.D. 21) than the women with the intermediate MBL genotype group B (283 days+/-S.D. 12) and the low MBL genotype group C (284 days+/-S.D. 9). This difference in mean gestational age is almost totally attributable to premature births in group A, since 12 of the 14 preterm births were from women with the high MBL genotype group A and only two from the intermediate MBL genotype group B.
We found an association between the maternal high MBL genotype group A and premature birth, suggesting that during pregnancy MBL-associated inflammation caused by higher MBL activity may contribute to earlier delivery. Furthermore, this finding might explain why so many individuals are MBL deficient in the general population.
Molecular Immunology 04/2008; 45(5):1514-8. · 2.90 Impact Factor
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ABSTRACT: Reactive arthritis (ReA) in tuberculosis (TB) is known as Poncet's disease. It is a rare aseptic form of arthritis observed in patients with active TB. We present two such patients and review the literature on Poncet's disease.
Two patients who were identified with Poncet's disease at the Department of Rheumatology of Erasmus MC, Rotterdam University Hospital, during the last 5 yrs are reported. In addition, a review of the literature on Poncet's disease is given: the PubMed/MEDLINE database was studied up to December 2005 using the term 'Poncet's disease' and the terms 'arthritis', 'reactive' and 'tuberculosis'.
After careful work-up, the polyarthritis and erythema nodosum in both presented patients with active TB could be diagnosed as Poncet's disease. Resolution of the arthritis with anti-TB drugs occurred in just a few days. Reviewing the literature, 50 case reports were found. In most reports 'Poncet's disease' was described as an aseptic polyarthritis, presumably ReA arthritis developing in the presence of active TB elsewhere. However, no uniform characterization of the term 'Poncet's disease' could be abstracted from these reports.
Both presented patients and the review of the literature demonstrate that active TB may be complicated by ReA known as Poncet's disease. Early recognition of this rare complication of TB is of major importance to avoid delayed initiation of appropriate treatment.
Rheumatology 04/2007; 46(3):484-9. · 4.06 Impact Factor
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ABSTRACT: Pregnancy is associated with changes in the immune system. Although previous studies have focussed mainly on adaptive immunity, there are indications that components of innate immunity, such as mannose-binding lectin (MBL), are associated with pregnancy outcome. Although this would suggest that pregnancy also involves adaptations in innate immunity, there are few studies in this area. Therefore, we aimed to determine whether MBL concentrations and the following steps in complement pathway activation are influenced by pregnancy.
MBL and Ficolin-2 concentrations, MBL-MBL-associated serine protease (MASP) complex activity, MBL pathway activity and classical complement pathway activity were determined by enzyme-linked immunosorbent assay (ELISA) in sera from pregnant women (n=32) during each trimester and post-partum. MBL genotyping was performed by PCR.
During pregnancy, MBL concentrations increased to 140% [interquartile range (IQR) 116-181%, P < 0.0001]. This increase was already present at 12 weeks of pregnancy and was most pronounced in the high-production AA-genotype. Directly Post-partum MBL concentrations dropped to 57% of baseline (IQR 44-66%, P < 0.0001). Variations in MBL levels were reflected by similar changes in the following steps of complement activation, r > 0.93 (P < 0.01). Ficolin-2 levels and classical complement pathway activity were not similarly influenced by pregnancy.
Pregnancy and the post-partum period profoundly influence MBL serum concentration and MBL complement pathway activity.
Human Reproduction 03/2007; 22(2):362-71. · 4.47 Impact Factor
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Clinical Nuclear Medicine 09/2006; 31(8):501-3. · 3.67 Impact Factor
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ABSTRACT: To assess the diagnostic value of blindly performed synovial biopsies in carefully selected patients with unclassified arthritis.
Synovial tissue was obtained blindly under local anaesthesia. The Arthroforce III take-apart 3.5 mm needle and 1.5 mm grasping forceps were used for this purpose.
Four patients with unclassified arthritis could be diagnosed properly based upon examination of synovial tissue of the knee obtained by an easy-to-perform blind biopsy. The arthritis of the four patients was diagnosed as being part of Erdheim-Chester disease, sarcoidosis, multicentric reticulohistiocytosis and arthritis caused by foreign-body material, respectively.
Analysis of synovial tissue obtained during a blind biopsy procedure has diagnostic potential in carefully selected patients with unclassified arthritis. The common denominator in all the cases presented was a differential diagnosis consisting of a rheumatological disease with characteristic histological features.
Rheumatology 03/2006; 45(2):192-5. · 4.06 Impact Factor
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ABSTRACT: To evaluate the performance of automated leucocyte (white blood cell; WBC) counting by comparison with manual counting.
The number of WBC was determined in heparinized synovial fluid samples by the use of (i) a standard urine cytometer (Kova) and a microscope (reference method) and (ii) a haematology analyser (Sysmex XE-2100; WBC/BASO and DIFF channels). Imprecision within and between days was determined by replicate analysis of a low (level A; WBC approximately 0.560 x 10(9)/l) and a high (level B; WBC approximately 1.081 x 10(9)/l) dedicated synovial fluid control (Quantimetrix).
The WBC count of the DIFF channel was highly correlated with the WBC count of the microscopic reference method (r = 0.99; WBC analyser = 0.870 x WBC reference method + 0.413). In contrast, no agreement existed between WBC counts generated by the WBC/BASO channel of the analyser and the reference method (r = 0.52; WBC analyser = 0.008 x WBC reference method + 0.079). Within-day imprecision (4-7%) and between-day imprecision (10%) of the haematology analyser were smaller than the within-day imprecision (12%) and the between-day imprecision (20-22%) of the manual reference method. For manual counting, inter-observer coefficients of variation were 35.9% (control level A) and 21.0% (control level B).
The WBC count in synovial fluid can be reliably determined using the DIFF channel of the Sysmex XE-2100. Automated counting of WBC in synovial fluid offers more precise and faster results than manual counting.
Rheumatology 03/2004; 43(2):170-3. · 4.06 Impact Factor
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ABSTRACT: BackgroundThe complement factor mannose-binding lectin (MBL) is associated with adverse pregnancy outcome. MBL serum concentrations are increased from early pregnancy onwards and depend upon several gene polymorphisms. We investigated whether MBL polymorphisms are associated with term and preterm birth, since preterm birth is the leading cause of neonatal morbidity and mortality.MethodsMBL2 gene polymorphisms were determined in 157 nulliparous women. Considering MBL polymorphisms cases were categorized in groups of high (A), intermediate (B) and low (C) MBL production. Kaplan–Meier survival and multiple linear regression analysis were performed.ResultsWomen with high MBL genotype group A had a shorter gestational age (274 days ± S.D. 21) than the women with the intermediate MBL genotype group B (283 days ± S.D. 12) and the low MBL genotype group C (284 days ± S.D. 9). This difference in mean gestational age is almost totally attributable to premature births in group A, since 12 of the 14 preterm births were from women with the high MBL genotype group A and only two from the intermediate MBL genotype group B.ConclusionsWe found an association between the maternal high MBL genotype group A and premature birth, suggesting that during pregnancy MBL-associated inflammation caused by higher MBL activity may contribute to earlier delivery.Furthermore, this finding might explain why so many individuals are MBL deficient in the general population.
Molecular Immunology.
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