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1.
Marotte H Pallot-Prades B Grange L Gaudin P Alexandre C Miossec P 《Arthritis research & therapy》2007,9(3):R61
The goal of the present study was to record changes in bone mineral density (BMD) and markers of bone turnover in patients
with rheumatoid arthritis (RA) who were treated with methotrexate combined (or not combined) with infliximab. Included were
90 patients with RA who required anti-TNF-α therapy with infliximab because of persistent active disease despite treatment
with methotrexate. The historical control group included 99 patients with RA who were treated with methotrexate at a time
when anti-TNF-α treatment was not yet available. Lumbar and femoral neck BMD was measured using dual energy X-ray absorptiometry
at baseline and 1 year later. Osteocalcin, C-terminal cross-linked telopeptide of type I collagen, parathyroid hormone and
25-hydroxycholecalciferol were measured in plasma at baseline and 1 year later. At 1 year BMD had decreased in the control
group at spine (P < 0.01) and femoral neck (P < 0.001). In contrast, BMD at spine and femoral neck did not change after 1 year of infliximab treatment. At the same time
point, no change in bone remodelling markers was observed. No association was observed between clinical response and changes
in BMD, indicating that even those who did not respond clinically did not lose bone over a 1-year period. These data confirm
the BMD decrease observed in RA patients treated with methotrexate alone. This bone loss was prevented by infliximab therapy.
Importantly, this beneficial effect was also observed in apparent nonresponders. 相似文献
2.
Jade E Hollis-Moffatt Michael Chen-Xu Ruth Topless Nicola Dalbeth Peter J Gow Andrew A Harrison John Highton Peter BB Jones Michael Nissen Malcolm D Smith Andre van Rij Gregory T Jones Lisa K Stamp Tony R Merriman 《Arthritis research & therapy》2010,12(3):1-11
Introduction
To investigate whether accelerated hand bone mineral density (BMD) loss is associated with progressive joint damage in hands and feet in the first year of rheumatoid arthritis (RA) and whether it is an independent predictor of subsequent progressive total joint damage after 4 years.Methods
In 256 recent-onset RA patients, baseline and 1-year hand BMD was measured in metacarpals 2-4 by digital X-ray radiogrammetry. Joint damage in hands and feet were scored in random order according to the Sharp-van der Heijde method at baseline and yearly up to 4 years.Results
68% of the patients had accelerated hand BMD loss (>-0.003 g/cm2) in the first year of RA. Hand BMD loss was associated with progressive joint damage after 1 year both in hands and feet with odds ratios (OR) (95% confidence intervals [CI]) of 5.3 (1.3-20.9) and 3.1 (1.0-9.7). In univariate analysis, hand BMD loss in the first year was a predictor of subsequent progressive total joint damage after 4 years with an OR (95% CI) of 3.1 (1.3-7.6). Multivariate analysis showed that only progressive joint damage in the first year and anti-citrullinated protein antibody positivity were independent predictors of long-term progressive joint damage.Conclusions
In the first year of RA, accelerated hand BMD loss is associated with progressive joint damage in both hands and feet. Hand BMD loss in the first year of recent-onset RA predicts subsequent progressive total joint damage, however not independent of progressive joint damage in the first year. 相似文献3.
Melek Güler-Yüksel Naomi B Klarenbeek Yvonne PM Goekoop-Ruiterman Jeska K de Vries-Bouwstra Sjoerd M van der Kooij Andreas H Gerards H Karel Ronday Tom WJ Huizinga Ben AC Dijkmans Cornelia F Allaart Willem F Lems 《Arthritis research & therapy》2010,12(3):R96
Introduction
To investigate whether accelerated hand bone mineral density (BMD) loss is associated with progressive joint damage in hands and feet in the first year of rheumatoid arthritis (RA) and whether it is an independent predictor of subsequent progressive total joint damage after 4 years.Methods
In 256 recent-onset RA patients, baseline and 1-year hand BMD was measured in metacarpals 2-4 by digital X-ray radiogrammetry. Joint damage in hands and feet were scored in random order according to the Sharp-van der Heijde method at baseline and yearly up to 4 years.Results
68% of the patients had accelerated hand BMD loss (>-0.003 g/cm2) in the first year of RA. Hand BMD loss was associated with progressive joint damage after 1 year both in hands and feet with odds ratios (OR) (95% confidence intervals [CI]) of 5.3 (1.3-20.9) and 3.1 (1.0-9.7). In univariate analysis, hand BMD loss in the first year was a predictor of subsequent progressive total joint damage after 4 years with an OR (95% CI) of 3.1 (1.3-7.6). Multivariate analysis showed that only progressive joint damage in the first year and anti-citrullinated protein antibody positivity were independent predictors of long-term progressive joint damage.Conclusions
In the first year of RA, accelerated hand BMD loss is associated with progressive joint damage in both hands and feet. Hand BMD loss in the first year of recent-onset RA predicts subsequent progressive total joint damage, however not independent of progressive joint damage in the first year. 相似文献4.
Daniel Aeberli Prisca Eser Harald Bonel Jolanda Widmer Gion Caliezi Pierre-Alain Varisco Burkhard Möller Peter M Villiger 《Arthritis research & therapy》2010,12(3):1-10
Introduction
The objective of this study was to assess three-dimensional bone geometry and density at the epiphysis and shaft of the third meta-carpal bone of rheumatoid arthritis (RA) patients in comparison to healthy controls with the novel method of peripheral quantitative computed tomography (pQCT).Methods
PQCT scans were performed in 50 female RA patients and 100 healthy female controls at the distal epiphyses and shafts of the third metacarpal bone, the radius and the tibia. Reproducibility was determined by coefficient of varia-tion. Bone densitometric and geometric parameters were compared between the two groups and correlated to disease characteristics.Results
Reproducibility of different pQCT parameters was between 0.7% and 2.5%. RA patients had 12% to 19% lower trabecular bone mineral density (BMD) (P ≤ 0.001) at the distal epiphyses of radius, tibia and metacarpal bone. At the shafts of these bones RA patients had 7% to 16% thinner cortices (P ≤ 0.03). Total cross-sectional area (CSA) at the metacarpal bone shaft of pa-tients was larger (between 5% and 7%, P < 0.02), and relative cortical area was reduced by 13%. Erosiveness by Ratingen score correlated negatively with tra-becular and total BMD at the epiphyses and shaft cortical thickness of all measured bones (P < 0.04).Conclusions
Reduced trabecular BMD and thinner cortices at peripheral bones, and a greater bone shaft diameter at the metacarpal bone suggest RA spe-cific bone alterations. The proposed pQCT protocol is reliable and allows measuring juxta-articular trabecular BMD and shaft geometry at the metacarpal bone. 相似文献5.
Kapetanovic MC Larsson L Truedsson L Sturfelt G Saxne T Geborek P 《Arthritis research & therapy》2006,8(4):R131-7
In the present study we evaluated the impact of baseline antinuclear antibody (ANA) status and use of methotrexate on development
of infliximab-related infusion reactions in patients with rheumatoid arthritis (RA) or spondylarthropathies (SpAs), including
psoriatic arthritis. All patients with RA (n = 213) or SpA (n = 76) treated with infliximab during the period 1999–2005 at the Department of Rheumatology in Lund, Sweden were included.
ANAs were present in 28% and 25% of RA and SpA patients, respectively. Because of differences in baseline characteristics,
we used a binary logistic regression model to calculate odds ratios (ORs), adjusting for age, sex and prednisolone dosage.
Altogether 21% of patients with RA and 13% of patients with SpA developed infusion reactions (P = 0.126). The OR for development of infusion reactions in RA patients with baseline ANA positivity alone was 2.1. Infliximab
without methotrexate and infliximab as monotherapy were associated with ORs of 3.1 and 3.6, respectively. Combining infliximab
without methotrexate and ANA positivity yielded an OR for infusion reaction of 4.6. Lower age at disease onset and longer
disease duration were associated with infusion reactions (P = 0.012 and P = 0.036, respectively), but age, sex, C-reactive protein, erythrocyte sedimentation rate, Health Assessment Questionnaire
and Disease Activity Score-28 at baseline were not. No predictors of infusions reactions were identified in SpA patients.
RA patients treated with infliximab without methotrexate, and who are positive at baseline for ANAs are at increased risk
for developing infliximab-related infusion reactions. 相似文献
6.
We conducted the present study to determine whether repair of erosions occurs in patients with rheumatoid arthritis (RA) treated
with conventional disease-modifying anti-rheumatic drugs (DMARDs) and to compare clinical characteristics between patients
exhibiting and not exhibiting erosion repair. We included in the study a total of 122 RA patients who fulfilled the 1987 American
College of Rheumatology criteria for RA; all patients had paired sequential radiographs of both hands and wrists showing erosive
changes at baseline. Patients were classified into two groups according to the presence of repair of erosions at follow up,
namely the 'repair observed' and 'repair not observed' groups. Clinical characteristics, disease activity, radiographic scores
and treatment in the two groups were compared. Forty-four repairs were observed in 13 patients (10.7%). Compared with the
repair not observed group, the functional class of the patients in the repair observed group was lower at baseline (P < 0.01) and the mean disease activity was lower at follow up (P < 0.005). The changes in radiographic scores per year (total radiographic score and erosion score) were lower (P < 0.05 and P < 0.01, respectively) in the repair observed group. No difference in treatment was observed. Repair of erosions was detected
in 10.7% of RA patients treated with conventional DMARDs. Repairs were associated with low functional class at baseline and
low disease activity at follow up. These observations support the importance of reduction in disease activity in RA patients.
Because repair of erosions was detected in a substantial number of patients, assessment of erosion repair should be incorporated
into the radiographic evaluation and scoring of RA. 相似文献
7.
Cecilia P Chung Annette Oeser Ingrid Avalos Tebeb Gebretsadik Ayumi Shintani Paolo Raggi Tuulikki Sokka Theodore Pincus C Michael Stein 《Arthritis research & therapy》2007,8(6):R186
The prevalence of ischemic heart disease and atherosclerosis is increased in patients with rheumatoid arthritis (RA). In the
general population, but not in patients with systemic lupus erythematosus, the Framingham risk score identifies patients at
increased cardiovascular risk and helps determine the need for preventive interventions. We examined the hypothesis that the
Framingham score is increased and associated with coronary-artery atherosclerosis in patients with RA. The Framingham score
and the 10-year cardiovascular risk were compared among 155 patients with RA (89 with early disease, 66 with long-standing
disease) and 85 control subjects. The presence of coronary-artery calcification was determined by electron-beam computed tomography.
The Framingham score was compared in patients with RA and control subjects, and the association between the risk score and
coronary-artery calcification was examined in patients. Patients with long-standing RA had a higher Framingham score (14 [11
to 18]) (median [interquartile range]) compared to patients with early RA (11 [8 to 14]) or control subjects (12 [7 to 14],
P < 0.001). This remained significant after adjustment for age and gender (P = 0.015). Seventy-six patients with RA had coronary calcification; their Framingham risk score was higher (14 [12 to 17])
than that of 79 patients without calcification (10 [5 to 14]) (P < 0.001). Furthermore, a higher Framingham score was associated with a higher calcium score (odds ratio [OR] = 1.20, 95%
confidence interval [CI] 1.12 to 1.29, P < 0.001), and the association remained significant after adjustment for age and gender (OR = 1.15, 95% CI 1.02 to 1.29, P = 0.03). In conclusion, a higher Framingham risk score is independently associated with the presence of coronary calcification
in patients with RA. 相似文献
8.
Yousry Mostafa Hussien Amal Shehata Rehab A. Karam Saad S. Alzahrani Hanem Magdy Abeer M. El-Shafey 《Molecular biology reports》2013,40(5):3675-3680
1α,25-Dihydroxyvitamin D3 upregulates the expression of the receptor activator of nuclear factor kB ligand (RANKL), and downregulates osteoprotegerin (OPG) expression. We tested the effects of polymorphisms in the vitamin D receptor gene (VDR), and OPG gene in rheumatoid arthritis (RA) patients and healthy controls and their relationship to bone mineral density (BMD) and development of osteoporosis. Three hundred and fifty women were evaluated, 200 women having RA and 150 healthy control. The subjects were genotyped for polymorphism at BsmI in VDR and A163G in OPG genes by polymerase chain reaction followed by restriction fragment length polymorphism analysis. BMD was also measured. In A163G, the G allele increased the risk for RA and for the development of osteoporosis. We found a significant association between lower hip (BMD-h) and genotype variants of VDR (BsmI) and OPG A163G in RA patients with osteoporosis. Our results suggested that OPG A163G polymorphism was associated with RA susceptibility and with the development of osteoporosis in these patients. Also, VDR and OPG genes are important candidates for osteoporosis in RA patients. 相似文献
9.
《Endocrine practice》2021,27(9):934-940
ObjectiveThis retrospective observational study assessed the long-term impact of pulsatile gonadotropin-releasing hormone, combined gonadotropin, or testosterone replacement therapy on total hip, femoral, and lumbar bone mineral density (BMD) and Z-scores in adult men with idiopathic hypogonadotropic hypogonadism (IHH).MethodsIn the cross-sectional study, 69 patients were allocated to untreated (n = 42) and treated (n = 27) groups. The untreated group included IHH patients without hormone therapy history, while the treated group included age- and body mass index-matched patients who had received hormone therapy for at least 5 years. The longitudinal study included 53 IHH patients, and their hip and lumbar BMDs were measured several times during hormone therapy. We then evaluated the changes in their BMD.ResultsOur cross-sectional study showed that the treated group had a significantly higher BMD and Z-score for total hip, femoral neck, and lumbar spine (P < 0.001 for all) than the untreated group, and the average bone mass even reached the age-matched normal range. The prevalence of low BMD was 80.95% and 11.11% in untreated and treated groups, respectively. In the longitudinal study (N = 53), the total hip, femoral neck, and lumbar spine BMD gradually increased during treatment. The lumbar spine showed a greater increment in BMD compared with the total hip and femoral neck (P < 0.05).ConclusionSex hormone therapy improved hip and lumbar spine BMD and Z-scores in patients with IHH. The lumbar spine showed a greater improvement in BMD compared with the total hip and femoral neck. 相似文献
10.
Rheumatoid arthritis (RA) patients experience a markedly increased frequency of cardiovascular disease. We evaluated cardiovascular risk profiles in 79 RA patients and in 39 age-matched and sex-matched osteoarthritis (OA) patients. Laboratory tests comprised ultrasensitive C-reactive protein (CRP) and fasting lipids. Insulin sensitivity (IS) was determined by the Quantitative Insulin Sensitivity Check Index (QUICKI) in all OA patients and in 39 of the RA patients. Ten RA patients were on glucocorticoids. RA patients exercised more frequently than OA patients (χ2 = 3.9, P < 0.05). Nine RA patients and one OA patient had diabetes (χ2 = 4.5, P < 0.05). The median CRP, the mean QUICKI and the mean high-density lipoprotein (HDL) cholesterol were 9 mg/l (range, 0.5–395 mg/l), 0.344 (95% confidence interval [CI], 0.332–0.355) and 1.40 mmol/l (95% CI, 1.30–1.49 mmol/l) in RA patients, respectively, as compared with 2.7 mg/l (range, 0.3–15.9 mg/l), 0.369 (95% CI, 0.356–0.383) and 1.68 mmol/l (95% CI, 1.50–1.85 mmol/l) in OA patients. Each of these differences was significant (P < 0.05). After controlling for the CRP, the QUICKI was similar in RA and OA patients (P = 0.07), while the differences in HDL cholesterol were attenuated but still significant (P = 0.03). The CRP correlated with IS, while IS was associated with high HDL cholesterol and low triglycerides in RA patients and not in OA patients. A high CRP (≥ 8 mg/l) was associated with hypertension (χ2 = 7.4, P < 0.05) in RA patients. RA glucocorticoid and nonglucocorticoid users did not differ in IS and lipids (P > 0.05). Excess cardiovascular risk in RA patients as compared with OA patients includes the presence of decreased IS and HDL cholesterol in RA patients. The latter is only partially attributable to the acute phase response. The CRP, IS, HDL cholesterol, triglycerides and hypertension are inter-related in RA patients, whereas none of these relationships were found in OA patients. 相似文献
11.
The aim of the present work is to compare drug survival and safety of infliximab, etanercept, and adalimumab (tumor necrosis
factor [TNF] antagonists) in spondylarthritis (SpA) with those of rheumatoid arthritis (RA). To this purpose, we analysed
the data in BIOBADASER (2000–2005), a drug registry launched in 2000 for long-term follow-up of the safety of these biologics
in rheumatic diseases. The rates of drug discontinuation and adverse events (AEs) in SpA (n = 1,524) were estimated and compared with those of RA (n = 4,006). Cox regression analyses were used to adjust for independent factors. Total exposure to TNF antagonists for SpA
was 2,430 patient-years and 7,865 for RA. Drug survival in SpA was significantly greater than in RA at 1, 2, and 3 years.
The hazard ratio (HR) for discontinuation in SpA compared with RA was 0.66 (95% confidence interval [CI], 0.57–0.76) after
adjustment for age, gender, and use of infliximab. The difference remained after controlling for the individual medication
and its place in the sequence of treatment. There were fewer SpA patients with AEs (17%) than RA patients (26%; p < 0.001). The HR for AEs in SpA was 0.80 (95% CI, 0.70–0.91) compared with RA after adjustment for age, disease duration,
and use of infliximab. In conclusion, due in part to a better safety profile, survival of TNF antagonists in SpA is better
than in RA. TNF antagonists are at present a safe and effective therapeutic option for long-term treatment of patients with
SpA failing to respond to traditional drugs. Because chronic therapy is necessary, continual review of this issue is necessary. 相似文献
12.
Pierer M Kaltenhäuser S Arnold S Wahle M Baerwald C Häntzschel H Wagner U 《Arthritis research & therapy》2006,8(3):R75-7
The functional single-nucleotide polymorphism (SNP) of the gene PTPN22 is a susceptibility locus for rheumatoid arthritis (RA). The study presented here describes the association of the PTPN22 1858T allele with RA in a German patient cohort; 390 patients with RA and 349 controls were enrolled in the study. For 123
patients, clinical and radiographic documentation over 6 years was available from the onset of disease. Genotyping of the
PTPN22 1858 SNP was performed using an restriction fragment length polymorphism PCR-based genotyping assay. The odds ratio to develop
RA was 2.57 for carriers of the PTPN22 1858T allele (95% confidence interval (CI) 1.85–3.58, p < 0.001), and 5.58 for homozygotes (95% CI 1.85–16.79). The PTPN22 1858T allele was significantly associated not only with rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP)
positive RA, but also with RF and anti-CCP negative disease. The frequency of the PTPN22 1858T allele was increased disproportionately in male patients (53.8% compared to 33.0% in female patients, p < 0.001), and the resulting odds ratio for male carriers was increased to 4.47 (95% CI 2.5–8.0, p < 0.001). Moreover, within the male patient population, the rare allele was significantly associated with the HLA-DRB1 shared epitope (p = 0.01). No significant differences in disease activity or Larsen scores were detected. The results provide further evidence
that the PTPN22 1858T allele is associated with RA irrespective of autoantibody production. The increased frequency of the risk allele in
male patients and its association with the shared epitope indicate that the genetic contribution to disease pathogenesis might
be more prominent in men. 相似文献
13.
Hydroxychloroquine decreases human MSC‐derived osteoblast differentiation and mineralization in vitro
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Tim Both H. Jeroen van de Peppel M. Carola Zillikens Marijke Koedam Johannes P. T. M. van Leeuwen P. Martin van Hagen Bram C. J. van der Eerden 《Journal of cellular and molecular medicine》2018,22(2):873-882
We recently showed that patients with primary Sjögren Syndrome (pSS) have significantly higher bone mineral density (BMD) compared to healthy controls. The majority of those patients (69%) was using hydroxychloroquine (HCQ), which may have favourable effects on BMD. To study the direct effects of HCQ on human MSC‐derived osteoblast activity. Osteoblasts were cultured from human mesenchymal stromal cells (hMSCs). Cultures were treated with different HCQ doses (control, 1 and 5 µg/ml). Alkaline phosphatase activity and calcium measurements were performed to evaluate osteoblast differentiation and activity, respectively. Detailed microarray analysis was performed in 5 µg/ml HCQ‐treated cells and controls followed by qPCR validation. Additional cultures were performed using the cholesterol synthesis inhibitor simvastatin (SIM) to evaluate a potential mechanism of action. We showed that HCQ inhibits both MSC‐derived osteoblast differentiation and mineralization in vitro. Microarray analysis and additional PCR validation revealed a highly significant up‐regulation of the cholesterol biosynthesis, lysosomal and extracellular matrix pathways in the 5 µg/ml HCQ‐treated cells compared to controls. Besides, we demonstrated that 1 µM SIM also decreases MSC‐derived osteoblast differentiation and mineralization compared to controls. It appears that the positive effect of HCQ on BMD cannot be explained by a stimulating effect on the MSC‐derived osteoblast. The discrepancy between high BMD and decreased MSC‐derived osteoblast function due to HCQ treatment might be caused by systemic factors that stimulate bone formation and/or local factors that reduce bone resorption, which is lacking in cell cultures. 相似文献
14.
Kapetanovic MC Lindqvist E Algulin J Jonsson K Saxne T Eberhardt K Geborek P 《Arthritis research & therapy》2011,13(1):R31
Introduction
Changes in bone mineral density (BMD) in the hand as evaluated by digital X-ray radiogrammetry (DXR) of the second to fourth metacarpal bones has been suggested to predict future joint damage in patients with rheumatoid arthritis (RA). This study's objective was to investigate whether DXR-BMD loss early in the course of the disease predicts the development of joint damage in RA patients followed for up to 20 years. 相似文献15.
Zhi-Chao Yuan Jia-Min Wang Lin-Chong Su Wang-Dong Xu An-Fang Huang 《Journal of cellular physiology》2019,234(7):11760-11767
Recent findings showed elevated expression of tumor necrosis factor (TNF)-like ligand 1A (TL1A) in rheumatoid arthritis (RA) patients and arthritis mice. However, whether TL1A gene polymorphisms may correlate with RA susceptibility needs to be discussed. This case-control study was performed on 350 RA patients and 556 healthy subjects to identify TL1A genetic variants (rs3810936, rs6478109, and rs7848647) and their possible association with TL1A levels, susceptibility to and severity of RA. Odds ratio and 95% confidence interval were calculated to represent the correlation between TL1A polymorphisms and RA. The TL1A serum levels were evaluated. Results showed that frequencies of TC, TT + TC genotypes of rs3810936, rs7848647 in RA patients were significantly lower in RA patients compared with controls. Patients with C allele showed more severe disease course (disease activity index: erythrocyte sedimentation rate, rheumatoid factor) than in carriers of T allele. However, the allele or genotype frequencies of rs6478109 were not associated with RA. In addition, TL1A genetic variants conferred higher TL1A levels in RA patients compared with controls. In conclusion, these findings indicated an association between TL1A rs3810936, rs7848647 variation and the susceptibility of RA in a sample of Chinese individuals, and TL1A may correlate with severity of RA. 相似文献
16.
Pernille Bøyesen Mari Hoff Sigrid Ødegård Glenn Haugeberg Silje W Syversen Per I Gaarder Cecilie Okkenhaug Tore K Kvien 《Arthritis research & therapy》2009,11(4):R103-9
Introduction
Radiographic progression in rheumatoid arthritis (RA) has in several studies been shown to be predicted by serological markers widely used in daily clinical practice. The objective of this longitudinal study was to examine if these serological markers also predict hand bone mineral density (BMD) loss in patients with RA of short disease duration. 相似文献17.
Tissue inhibitors of matrix metalloproteinases (TIMPs) regulate the breakdown of extracellular matrix components and play
an important role in tissue remodelling and growth, in both physiological and pathological conditions. We studied the autoimmune
response to TIMPs in patients with rheumatoid arthritis (RA). Eighty-nine paired blood and synovial fluid samples from patients
with RA were assessed for their reactivity with recombinant tissue inhibitors of metalloproteinases (TIMPs) 1 to 4 by an ELISA
and were compared with blood from 62 healthy controls and 21 synovial fluid samples from patients with degenerative joint
diseases. Presence of antibodies was established as the absorbance of the sample more than 2 standard deviations above the
mean of the controls. In addition, immunoglobulin G (IgG) from blood samples of RA patients possessing TIMP antibodies was
isolated on protein A–sepharose and tested for the in vitro ability to neutralize TIMP-2-dependent effects on metalloproteinase 9 (MMP9). Anti-TIMP antibodies were found in 56% of RA
samples but in only 5% of the controls (P < 0.005). RA patients had high frequencies of antibodies against all TIMPs except TIMP-3. TIMP-2 antibodies were most frequently
found (33%), being significantly more prevalent (P = 0.024) in patients with nonerosive than erosive RA. TIMP-1 antibodies were significantly more often found in synovial fluid
samples than in the matched blood samples (P < 0.025). Importantly, the IgG fraction containing TIMP antibodies down-regulated the TIMP-2 inhibitory effect, thereby supporting
MMP9 activity in vitro. In the present study, we show that RA patients frequently develop autoimmune response to TIMPs that may act as a functionally
significant regulator of MMP activity and thereby of joint destruction. 相似文献
18.
Masahiro Iwamoto Eleanor B. Golden Sherrill L. Adams Sumihare Noji Maurizio Pacifici 《Experimental cell research》1993,205(2)
We previously showed that retinoic acid (RA) participates in the regulation of chondrocyte maturation during endochondral ossification, a process involving multiple developmental stages. To assess whether the responsiveness to RA treatment changes during chondrocyte maturation, immature chondrocytes were isolated from the caudal portion of Day 18-19 chick embryo sterna, a portion that remains cartilaginous through early postnatal life but ossifies with age. The immature cells were allowed to reach different stages of maturation by growth for different time in culture. Progression by the cells toward the mature phenotype during culture was confirmed by increases in average cell diameter, proteoglycan synthesis, and alkaline phosphatase (APase) activity. When developmentally immature passage 0 (PO) cultures were treated with RA (10-100 nM) for 72 h, the cells readily became fibroblastic, reduced drastically their proteoglycan synthesis, and failed to activate type X collagen gene expression. When older cultures (P1 and P2) were treated with RA, the cells acquired a characteristic epithelioid shape and increased their APase activity. Moreover, 5-10% of P1 cells and 20-25% of P2 cells activated type X collagen synthesis in response to RA. RA treatment markedly induced expression of the gene encoding the β isoform of retinoic acid receptor (RARβ) and also provoked a moderate 2.5-fold increase in RARα gene expression. A similar change in responsiveness to RA was observed during maturation in vivo. Chondrocytes were isolated from the cephalic portion of Day 10, 11, 13, and 16 chick embryo sterna, and were treated with different doses of RA (10-100 nM) for 72 h. The cells from the Day 10 sternum failed to activate type X collagen gene expression in response to RA. In contrast, with increasing age of the embryos, an increasing fraction of cells induced type X collagen gene expression in response to RA. We conclude that responsiveness to RA changes during the early stages of chondrocyte maturation and that maturation depends on interactions between exogenous retinoids and the endogenous developmental program of chondrocytes. 相似文献
19.
Flendrie M Vissers WH Creemers MC de Jong EM van de Kerkhof PC van Riel PL 《Arthritis research & therapy》2005,7(3):R666-R676
Various dermatological conditions have been reported during tumor necrosis factor (TNF)-α-blocking therapy, but until now
no prospective studies have been focused on this aspect. The present study was set up to investigate the number and nature
of clinically important dermatological conditions during TNF-α-blocking therapy in patients with rheumatoid arthritis (RA).
RA patients starting on TNF-α-blocking therapy were prospectively followed up. The numbers and natures of dermatological events
giving rise to a dermatological consultation were recorded. The patients with a dermatological event were compared with a
group of prospectively followed up RA control patients, naive to TNF-α-blocking therapy and matched for follow-up period.
289 RA patients started TNF-α-blocking therapy. 128 dermatological events were recorded in 72 patients (25%) during 911 patient-years
of follow-up. TNF-α-blocking therapy was stopped in 19 (26%) of these 72 patients because of the dermatological event. More
of the RA patients given TNF-α-blocking therapy (25%) than of the anti-TNF-α-naive patients (13%) visited a dermatologist
during follow-up (P < 0.0005). Events were recorded more often during active treatment (0.16 events per patient-year) than during the period
of withdrawal of TNF-α-blocking therapy (0.09 events per patient-year, P < 0.0005). The events recorded most frequently were skin infections (n = 33), eczema (n = 20), and drug-related eruptions (n = 15). Other events with a possible relation to TNF-α-blocking therapy included vasculitis, psoriasis, drug-induced systemic
lupus erythematosus, dermatomyositis, and a lymphomatoid-papulosis-like eruption. This study is the first large prospective
study focusing on dermatological conditions during TNF-α-blocking therapy. It shows that dermatological conditions are a significant
and clinically important problem in RA patients receiving TNF-α-blocking therapy. 相似文献
20.
Lotta Ljung Johan Askling Solbritt Rantap??-Dahlqvist Lennart Jacobsson 《Arthritis research & therapy》2014,16(3):R127