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ID PMID Title PublicationDate abstract
15948014 Intra-articular methotrexate in the treatment of rheumatoid arthritis and psoriatic arthri 2006 Mar The aim of our study was to evaluate the effects of intra-articular methotrexate (MTX) in patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA). Twenty-three consecutive patients, 10 with RA and 13 with PsA, with prevalent or unique arthritic involvement of one knee, were treated with intra-articular injections of MTX 10 mg every 7 days for 8 weeks. Before the beginning of the treatment and after 9 and 17 weeks, the patients underwent a clinical evaluation measuring maximal knee flexion angle, visual analog scale (VAS) and erythrocyte sedimentation rate (ESR). On the same days, an ultrasonographic examination of the involved knee was performed by two independent experienced operators. Synovial thickness in the suprapatellar bursa and the presence of joint effusion and Baker's cyst were assessed. An increase of the mean value of maximal knee flexion angle and a reduction of the mean values of ESR and VAS between T0, T9 and T17 were demonstrated. Ultrasonographic evaluation showed significant reduction of synovial thickness and joint effusion. No differences were detected for the presence of Baker's cyst. We may conclude that repeated intra-articular injections of MTX resulted in a decrease of local as well as systemic inflammatory signs. As far as we know, this is the first study that explores the effects of intra-articular MTX in RA and PsA both clinically and by ultrasonography.
16174490 Neuroendocrine-immune aspects of accelerated aging in rheumatoid arthritis. 2005 Oct The normal process of aging brings about changes in immune function, hormonal status, overall metabolism, and enhanced occurrence of neuropsychiatric disorders. These alterations are also evident at an accelerating pace in chronic inflammatory diseases. Treatment with immunosuppressive therapeutics is often not sufficiently effective. Treating neuroendocrine-immune alterations to regain homeostasis might enhance remission inducing and maintaining effects. This paper summarizes the phenomena related to normal aging and related to chronic inflammatory disease. Furthermore, a multimodal concept is being proposed to control more effectively chronic inflammatory disease on a neuroendocrine-immune basis.
16758512 The frequency and distribution of minocycline induced hyperpigmentation in a rheumatoid ar 2006 Jul OBJECTIVE: Minocycline is particularly useful in patients with rheumatoid arthritis (RA) with previous major sepsis, where anti-tumor necrosis factor is relatively contraindicated. Pigmentation is a documented side effect, but predisposing factors in an RA population have not been established. We investigated minocycline induced pigmentation in a population with RA to determine whether skin type and eye color influence predisposition to this side effect. METHODS: Patients with RA attending a rheumatology unit who had received minocycline were contacted by telephone and some were also interviewed in the clinic. Those receiving therapy for more than 3 months were assessed. Hair color, eye color, tendency to burn in the sun, and dose and duration of therapy were documented. The frequency, type, and distribution of pigmentation were established. RESULTS: Of 37 patients identified, 10 were excluded because the duration of therapy was less than 3 months. Of the remaining 27 patients, 85% were female, with median age 64 years (range 44-88) and median disease duration 23.5 years (range 4-51). Eleven patients (41%) developed pigmentation after a median of 12 months. Four of the 11 stopped their minocycline due to pigmentation. Hair color, eye color, and tendency to burn in the sun did not predict patients who developed pigmentation. CONCLUSION: Pigmentation is a common side effect in patients receiving minocycline therapy for more than 3 months. Most patients do not stop therapy due to pigmentation. Those who stop are more likely to be female, less than 70 years of age, and have facial pigmentation.
16611864 Cigarette smoking and the risk of systemic lupus erythematosus and rheumatoid arthritis. 2006 May Smoking may affect the disease course in SLE and patients should be counselled to stop
16691188 High-density SNP analysis of 642 Caucasian families with rheumatoid arthritis identifies t 2006 Jun We have completed a genome wide linkage scan using >5700 informative single-nucleotide polymorphism (SNP) markers (Illumina IV SNP linkage panel) in 642 Caucasian families containing affected sibling pairs with rheumatoid arthritis (RA), ascertained by the North American Rheumatoid Arthritis Consortium. The results show striking new evidence of linkage at chromosomes 2q33 and 11p12 with logarithm of odds (LOD) scores of 3.52 and 3.09, respectively. In addition to a strong and broad linkage interval surrounding the major histocompatibility complex (LOD>16), regions with LOD>2.5 were observed on chromosomes 5 and 10. Additional linkage evidence (LOD scores between 1.46 and 2.35) was also observed on chromosomes 4, 7, 12, 16 and 18. This new evidence for multiple regions of genetic linkage is partly explained by the significantly increased information content of the Illumina IV SNP linkage panel (75.6%) compared with a standard microsatellite linkage panel utilized previously (mean 52.6%). Stratified analyses according to whether or not the sibling pair members showed elevated anticyclic citrullinated peptide titers indicates significant variation in evidence for linkage among strata on chromosomes 4, 5, 6 and 7. Overall, these new linkage data should reinvigorate efforts to utilize positional information to identify susceptibility genes for RA.
16238866 The self-regulatory model in women with rheumatoid arthritis: relationships between illnes 2005 Nov OBJECTIVES: The self-regulatory model proposes that an individual's cognitive representations of illness threat (illness representations) influence the selection and performance of strategies to cope with that illness (Leventhal, Meyer, & Nerenz, 1980). Also implicit in the model is the proposal that such coping strategies influence illness outcomes. These relationships represent a mediational model (Baron & Kenny, 1986). The aim of the present study is to test the hypothesis that coping strategies partially mediate the relationship between illness representations and illness outcome in women with rheumatoid arthritis. DESIGN AND METHODS: The study is an observational cross-sectional design. Self-report measures of illness representations, coping strategies, and illness outcome were collected from 125 women with rheumatoid arthritis attending rheumatology outpatient clinics. Clinical measures of disease activity and severity were obtained from hospital records. RESULTS: Avoidant and resigned coping were found to partially mediate the relationship between symptom identity and the illness outcome measures of disability and psychiatric morbidity. As in other studies, strong relationships were found between illness representations and illness outcome. CONCLUSIONS: The finding that avoidant and resigned coping partially mediated the relationships between the illness representation dimension of symptom identity and two of the illness outcome measures (disability and psychiatric morbidity) provided some support for the hypothesis. However, the hypothesis was not fully supported, as coping did not partially mediate the relationship between any of the other illness representations and illness outcomes.
17225293 The comparative efficacy and safety of biologics for the treatment of rheumatoid arthritis 2006 Dec OBJECTIVE: Biologics are an important therapeutic option for treating patients with rheumatoid arthritis (RA). However, they are associated with rare but severe adverse events such as serious infections, lymphoma, or chronic heart failure. In addition, dosing regimens and routes of administration differ substantially among biologics. In a systematic review, we assessed the comparative efficacy and safety of biologic agents for RA. METHODS: We searched electronic databases up to May 2006. We limited evidence to controlled trials for efficacy but included observational evidence for safety. Outcomes of interest were clinical response, radiographic progression, and quality of life. Given the paucity of head-to-head evidence, we conducted adjusted, indirect comparisons of placebo-controlled trials. RESULTS: Twenty-six controlled trials provided efficacy data; 18 additional studies assessed safety. The only evidence directly comparing 2 biologic agents was a nonrandomized, open-label trial that found no differences in effectiveness and safety between etanercept and infliximab. Adjusted indirect comparisons indicate no significant differences in efficacy between anti-tumor necrosis factor (TNF) drugs. However, anti-TNF drugs appear to be more efficacious than anakinra, although not all comparisons reached statistical significance. Because of the lack of sound longterm safety data, evidence is insufficient to draw firm conclusions about the comparative safety of biologics. CONCLUSION: Anti-TNF drugs appear to be more efficacious than anakinra but do not differ significantly among each other. Clinical considerations such as comorbidities, route of administration, dosing regimens, and specific side effect profiles may guide the choice of an anti-TNF drug.
17170054 Validation of the ABILHAND questionnaire as a measure of manual ability in patients with r 2007 Aug OBJECTIVE: Hand and upper limb involvement is common in patients with rheumatoid arthritis (RA). However, its impact on manual activities of daily life has not been fully evaluated. A measure of manual ability was developed, through the Rasch measurement model, by adapting and validating the ABILHAND questionnaire, which measures the patient's perceived difficulty in performing everyday manual activities. METHODS: 112 patients with RA were evaluated. The following tests were performed: the ABILHAND questionnaire, the Health Assessment Questionnaire (HAQ), the Jamar grip and key pinch strength tests, the Box and Block dexterity test and the Purdue pegboard dexterity test. In total, 35 patients were reassessed to determine the test-retest reliability of the ABILHAND, and 6 patients were studied before and after therapy with tumour necrosis factor (TNF) blockers to address sensitivity to change. RESULTS: The Rasch refinement of the ABILHAND led to a selection of 27 items rated on a 3-point scale. The resulting ability scale was targeted to the ability of the patients. The item-difficulty hierarchy was stable across demographic and clinical subgroups and over time. Grip and key pinch strength and manual and digital dexterity on both hands were significantly, though moderately, correlated with the ABILHAND measures. Manual ability was also significantly related to the number of affected hands, disease duration, tender and swollen joint counts on upper limbs, disease activity and the HAQ. Sensitivity to change was demonstrated in patients treated with TNF blockers, commensurate with their clinical improvement. CONCLUSION: The ABILHAND questionnaire is a clinically valid person-centred measure of manual ability that could be useful in longitudinal RA studies.
16652437 Adalimumab for treating rheumatoid arthritis. 2006 Jun OBJECTIVE: To assess the efficacy and safety of adalimumab in the treatment of rheumatoid arthritis (RA). METHODS: A Cochrane systematic review was performed. The literature search, selection and assessment of the methodological quality of the studies, and the data extraction were performed according to the standard methodology of the Cochrane reviews. Outcome measures included American College of Rheumatology (ACR) and European League Against Rheumatism responses, Disease Activity Score 28 and components of the ACR response, and radiographic and safety data. Weighted mean difference and relative risk were used for reporting continuous and dichotomous data, respectively. Number needed to treat (NNT) or to harm (NNH) were estimated when appropriate. When significant heterogeneity was not found, data were pooled. RESULTS: Six studies with 2,390 patients were included in this review. With adalimumab 40 mg every other week (eow) + methotrexate versus placebo + methotrexate, the absolute risk differences to achieve an ACR20, ACR50, and ACR70 response at 52 weeks were 35%, 32%, and 19% with NNT of 2.9, 3.1, and 5.3, respectively. At 52 weeks, adalimumab 40 mg eow and 20 mg every week (ew) significantly slowed the radiological progression. With adalimumab 40 mg eow versus placebo, the absolute risk differences to achieve an ACR20, ACR50, and ACR70 response at 24/26 weeks were 23.64%, 15.31%, and 12.22% with NNT of 5.0, 7.0, and 9.0, respectively. In most of the analyzed studies and comparisons, there were no significant differences in safety outcomes between adalimumab and control groups. CONCLUSION: On the basis of studies reviewed here, adalimumab is efficacious in the treatment of RA. No serious adverse effects occurred.
15940560 Ultrasonographic evaluation of tendons and enthesal sites in rheumatoid arthritis: compari 2005 Jun The objective of this study was to determine tendon involvements and enthesal abnormalities in patients with rheumatoid arthritis (RA) using high-resolution ultrasonographic images and to compare the findings with those seen in patients with ankylosing spondylitis (AS) and healthy controls. A total of 24 patients with RA, 18 with AS, and 20 healthy controls matched by age and body mass index (BMI) were included in the study. All of the patients and controls underwent clinical and ultrasonographic examinations of both lower limbs at five enthesal sites (superior and inferior pole of the patella, tibial tuberosity, Achilles tendon, and plantar aponeurosis) and both upper limbs at two tendon sites (tendons of m. biceps brachii and supraspinatus at the shoulder). High-resolution ultrasonographic examinations were performed to detect bursitis, structure thickness, bony erosion, and enthesophyte. An ultrasonographic score of lower limb enthesitis was calculated using the Glasgow Ultrasound Enthesitis Scoring System (GUESS) in all patients. Tendon involvements and enthesal abnormalities were found significantly more often in the RA group than in controls (p<0.05 to <0.001), but were not found to be different from the AS group (p>0.05). On clinical examination 67 of 336 (19.9%) tendon and enthesal sites were abnormal and on ultrasonographic examination 130 of 336 (38.2%) sites were abnormal in RA patients. The most frequently affected enthesal sites in the lower limbs were suprapatellar, infrapatellar, and Achilles tendon in both the RA and AS groups. The tibial tuberosity was less affected in both groups, and involvement of the plantar aponeurosis was not different from the controls. A statistically significant correlation was found between the Ritchie articular index and GUESS (r=0.578, p=0.008). Tendon involvements and enthesal abnormalities in RA patients were found more often than had been estimated. Further studies are required to validate our results.
15829572 Risks of solid cancers in patients with rheumatoid arthritis and after treatment with tumo 2005 Oct BACKGROUND: Existing studies of solid cancers in rheumatoid arthritis (RA) reflect cancer morbidity up until the early 1990s in prevalent cohorts admitted to hospital during the 1980s. OBJECTIVE: To depict the cancer pattern of contemporary patients with RA, from updated risk data from prevalent and incident RA populations. To understand the risk of solid cancer after tumour necrosis factor (TNF) treatment by obtaining cancer data from cohorts treated in routine care rather than trials. METHODS: A population based study of three RA cohorts (one prevalent, admitted to hospital 1990-2003 (n = 53,067), one incident, diagnosed 1995-2003 (n = 3703), and one treated with TNF antagonists 1999-2003 (n = 4160)), which were linked with Swedish nationwide cancer and census registers and followed up for cancer occurrence through 2003. RESULTS: With 3379 observed cancers, the prevalent RA cohort was at marginally increased overall risk of solid cancer, with 20-50% increased risks for smoke related cancers and +70% increased risk for non-melanoma skin cancer, but decreased risk for breast (-20%) and colorectal cancer (-25%). With 138 cancers, the incident RA cohort displayed a similar cancer pattern apart from non-decreased risks for colorectal cancer. TNF antagonist treated patients displayed solid cancer (n = 67) risks largely similar to those of other patients with RA. CONCLUSION: The cancer pattern in patients treated with TNF antagonists mirrors those of other contemporary as well as historic RA cohorts. The consistent increase in smoking associated cancers in patients with RA emphasises the potential for smoking cessation as a cancer preventive measure in RA.
17137624 Simultaneous diagnosis of CD3+ T-cell large granular lymphocyte leukaemia and true thymic 2007 Jul CD3+ T-cell large granular lymphocyte (LGL) leukaemia is a mature T-cell neoplasm of cytotoxic T-lymphocytes. Neutropenia represents the most frequent peripheral blood cytopenia associated with CD3+ T-cell LGL leukaemia. A wide variety of diseases associated with LGL leukaemia have been reported, both autoimmune and neoplastic. We describe for the first time the association of true thymic hyperplasia with CD3+ T-cell line LGL leukaemia. The patient presented with severe symptomatic neutropenia. Complete and persistent haematological and molecular remission was induced with an association of low-dose methotrexate and cyclosporin A, followed by thymectomy.
17057566 The validity and reliability of the graphic rating scale and verbal rating scale for measu 2006 Nov OBJECTIVE: To compare the validity and reliability of a graphic rating scale (GRS) and a verbal rating scale (VRS) for measuring pain intensity in young female Egyptian and Dutch patients with rheumatoid arthritis (RA). METHODS: Data were obtained in a cross-cultural study of 42 Egyptian and 30 Dutch female outpatients with stable RA. Construct validity was assessed by correlating the scales with other core measures of disease activity in RA. Test-retest reliability was assessed over a 1-week interval. RESULTS: The GRS and the VRS were strongly intercorrelated in the total study cohort and in the Egyptian and Dutch subgroups. In the individual subgroups, only the GRS demonstrated the expected pattern of correlations with other disease activity measures. Test-retest reliability of the GRS was adequate in both Egyptian and Dutch patients (intraclass correlation coefficient 0.78 vs. 0.83, respectively), whereas reliability of the VRS was unsatisfactory in the Egyptian subgroup (weighted kappa 0.60 vs. 0.82 in the Netherlands). DISCUSSION: The study confirmed that the GRS and VRS were reliable and valid in the total study cohort. Within the individual countries, the GRS seemed to perform better than the VRS.
17207385 Cardiovascular and pupillary autonomic nervous dysfunction in patients with rheumatoid art 2006 Nov OBJECTIVES: Patients with inflammatory diseases often demonstrate autonomic nervous dysfunction. This study was initiated to investigate cardiovascular (CAD) or pupillary autonomic dysfunction (PAD) in patients with rheumatoid arthritis (RA). METHODS: Between 1997 and 1998, 33 RA patients were examined for characteristics, and parameters of CAD and PAD. In a longitudinal part of this study, thirty patients have been re-evaluated 8.3 +/- 0.1 yr later (response rate = 91%). RESULTS: A total of 18 patients (60%) demonstrated either CAD or PAD. The prevalence of CAD was 6/30 (20%) and the prevalence of PAD was 15/30 (50%). Of all cardiovascular tests, the Ewing test demonstrated the worst results (13/30 patients were below the 5th percentile). Similar as in other diseases, several RA patients demonstrated autonomic nervous hyperreflexia with values above the 95 th percentile (relative variation coefficient: 7/30; respiratory sinus arrhythmia measure: 12/30; Valsalva measure: 1/30; Ewing measure: 0/30; latency time of pupillary light reflex: 5/30; maximal pupillary area: 0/30). During the 8-year observation period, 4/30 RA patients died. Non-survivors as compared to survivors had increased heart rate variation in the respiratory arrhythmia test (p= 0.038, hyperreflexia) but largely decreased heart rate variation in the Ewing test (p= 0.009, hyporeflexia). Non-survivors as compared to survivors demonstrated more frequent pupillary autonomic dysfunction (100% vs. 42%, p= 0.035). CONCLUSION: This study demonstrates that CAD and PAD were frequent in patients with RA. Patients with a poor test result in the Ewing test and PAD might have an increased risk of death. This study in RA patients demonstrates similar results as in patients with diabetes mellitus.
16142861 Prevalence of rheumatoid arthritis in the South-Transdanubian region of Hungary based on a 2005 Sep OBJECTIVE: To assess the prevalence of rheumatoid arthritis (RA) in a representative study of the South Transdanubian region of Hungary. METHODS: Ten thousand individuals aged between 14-65 years were interviewed. The stratified sample was representative for age, sex and urban/rural residence structure of the regional population of the South-West Hungarian region. As a second step, all individuals with possible RA were asked to undergo a clinical investigation to confirm the diagnosis of RA according to the American Rheumatism Association (ARA) 1987 criteria. Of 10,000 interviewed individuals, 632 reported having RA or symptoms including digital pain, stiffness, and/or swelling. Two hundred and twenty-four individuals were investigated clinically. Individuals fulfilling the 1987 ARA criteria were considered as having definite RA, and their clinical data were evaluated. RESULTS: RA was confirmed in 13 cases. The male/female ratio was 3/10. The prevalence of RA among individuals aged 14-65 years was 0.37% (95% confidence interval, CI: 0.26-0.51), 0.23% (95% CI: 0.15-0.35) in men and 0.48% (95% CI: 0.35-0.64) in women. CONCLUSION: The prevalence of RA in the South Transdanubian region of Hungary is similar to those of other recent studies from other regions around the world.
16099338 Tumor necrosis factor-alpha microsatellite polymorphism association with rheumatoid arthri 2005 Sep BACKGROUND: Level of TNF-alpha increases significantly in synovial fluid of rheumatoid arthritis (RA) patients. It is proposed that tumor necrosis factor (TNF) microsatellite alleles may influence its expression and presumably can contribute to the disease severity. However, there is a lack of such study to predict any such association with RA in an Indian population. METHODS: In this study, we investigated the differential pattern of distribution of TNF microsatellite alleles in an Indian population and its association with RA. One hundred eighteen RA patients and 120 healthy individuals were genotyped for TNF microsatellite alleles using Genescan. Odds ratio was calculated to demonstrate the correlation between allelic distribution and clinical severity. RESULTS: The study shows that distribution of TNF microsatellite alleles in an Indian population is very different from other Asian Oriental and Western populations, except for some similarities with an Italian population. Frequency of microsatellite TNFd3 allele (9.24 vs. 3.85%, chi(2)=5.6, p < or =0.0179, OR=0.393, 95% CI=0.177-0.87) and more interestingly TNFd3 containing haplotypes has been found significantly reduced in patients. On the contrary, TNFb5 allele frequency increased in the patients (22.3 vs. 30.8%, chi(2)=4.4, p < or =0.036, OR=1.55, 95% CI=1.027-2.344) as compared to controls. Furthermore, significant increase in frequency of this allele in severe patients (22.3 vs. 33.8%, chi(2)=6.22, p < or =0.013, OR=1.78, 95% CI=1.132-2.798) along with the significant increase in haplotypes containing this allele supports the association of TNFb5 with disease severity. CONCLUSIONS: In an Indian population, TNFb5 may be considered as a risk factor, whereas TNFd3, unlike others, may be protective for RA.
16277675 Polymorphism in the tumour necrosis factor receptor II gene is associated with circulating 2005 Levels of soluble tumour necrosis factor receptors (sTNFRs) are elevated in the circulation of patients with rheumatoid arthritis (RA). Although these receptors can act as natural inhibitors of tumour necrosis factor-alpha, levels of sTNFRs in RA appear to be insufficient to prevent tumour necrosis factor-alpha induced inflammation. The factors that regulate circulating levels of sTNFRs are unclear, but polymorphisms in the tumour necrosis factor receptor genes may play a role. We investigated the relationship between polymorphisms in the tumour necrosis factor receptor I (TNF-RI) and II (TNF-RII) genes and levels of sTNFRs in two groups of Caucasian RA patients: one with early (disease duration < or = 2 years; n = 103) and one with established disease (disease duration > or = 5 years; n = 151). PCR restriction fragment length polymorphism analysis was used to genotype patients for the A36G polymorphism in the TNF-RI gene and the T676G polymorphism in TNF-RII. Levels of sTNFRs were measured using ELISA. We also isolated T cells from peripheral blood of 58 patients with established RA with known TNF-R genotypes, and release of sTNFRs into the culture medium was measured in cells incubated with or without phytohaemagglutinin. Serum levels of the two sTNFRs (sTNF-RI and sTNF-RII) were positively correlated in both populations, and the level of each sTNFR was significantly higher in the patients with established disease (P < 0.0001). Multiple regression analyses corrected for age, sex and disease duration revealed a significant trend toward decreasing sTNF-RI and sTNF-RII levels across the TNF-RII genotypes (TT > TG > GG) of patients with established disease (P for trend = 0.01 and P for trend = 0.03, respectively). A similar nonsignificant trend was seen for early disease. No relationship with the TNF-RI A36G polymorphism was observed. sTNFRs released by isolated T cells exhibited a similar trend toward decreasing levels according to TNF-RII genotype, although only the association with levels of sTNF-RII was significant. Strong correlations were found between levels of circulating sTNFRs and levels released by T cells in vitro. Our data indicate that the T676G polymorphism in TNF-RII is associated with levels of sTNFRs released from peripheral blood T cells, and with circulating levels of sTNFR in patients with RA.
16176994 Radiological outcome in rheumatoid arthritis is predicted by presence of antibodies agains 2006 Apr OBJECTIVE: To evaluate the significance of antibodies against cyclic citrullinated peptide (anti-CCP) and rheumatoid factors (RFs), before the onset of rheumatoid arthritis and when presenting as early disease (baseline), for disease activity and progression. METHODS: 93 of a cohort of 138 patients with early rheumatoid arthritis (<12 months of symptoms) had donated blood before symptoms of rheumatoid arthritis (defined as pre-patients) and were identified from among blood donors within the Medical Biobank of northern Sweden. Disease activity (erythrocyte sedimentation rate (ESR), C reactive protein, joint score, global visual analogue scale) and radiological destruction in hands and feet (Larsen score) were assessed at baseline and after two years. Anti-CCP antibodies and RFs were analysed using enzyme immunoassays. HLA shared epitope (SE) alleles (DRB1*0401/0404) were identified. RESULTS: Patients with anti-CCP antibodies before disease onset had significantly higher Larsen score at baseline and after two years. In multiple regression analyses baseline values of anti-CCP/IgA-RF/IgG-RF/IgM-RF, swollen joint count, and Larsen score significantly predicted radiological outcome at two years. In logistic regression analyses, baseline values of anti-CCP antibodies/IgA-RF, therapeutic response at six months, and swollen joint count/ESR significantly predicted radiological progression after two years. The baseline titre of anti-CCP antibodies was higher in patients with radiological progression and decreased significantly in those with response to therapy. SE allele carriage was associated with a positive test for anti-CCP antibodies in pre-patients and in early rheumatoid arthritis. CONCLUSIONS: Presence of anti-CCP antibodies before disease onset is associated with more severe radiological damage. The titre of anti-CCP antibodies is related to disease severity.
15987500 ADAMTS proteinases: a multi-domain, multi-functional family with roles in extracellular ma 2005 Members of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family are known to influence development, angiogenesis, coagulation and progression of arthritis. As proteinases their substrates include the von Willebrand factor precursor and extracellular matrix components such as procollagen, hyalectans (hyaluronan-binding proteoglycans including aggrecan), decorin, fibromodulin and cartilage oligomeric matrix protein. ADAMTS levels and activities are regulated at multiple levels through the control of gene expression, mRNA splicing, protein processing and inhibition by TIMP (tissue inhibitor of metalloproteinases). A recent screen of human cartilage has shown that multiple members of the ADAMTS family may be important in connective tissue homeostasis and pathology.
16846525 A cell-cycle independent role for p21 in regulating synovial fibroblast migration in rheum 2006 Rheumatoid arthritis (RA) is characterized by synovial hyperplasia and destruction of cartilage and bone. The fibroblast-like synoviocyte (FLS) population is central to the development of pannus by migrating into cartilage and bone. We demonstrated previously that expression of the cell cycle inhibitor p21 is significantly reduced in RA synovial lining, particularly in the FLS. The aim of this study was to determine whether reduced expression of p21 in FLS could alter the migratory behavior of these cells. FLS were isolated from mice deficient in p21 (p21(-/-)) and were examined with respect to growth and migration. p21(-/-) and wild-type (WT) FLS were compared with respect to migration towards chemoattractants found in RA synovial fluid in the presence and absence of cell cycle inhibitors. Restoration of p21 expression was accomplished using adenoviral infection. As anticipated from the loss of a cell cycle inhibitor, p21(-/-) FLS grow more rapidly than WT FLS. In examining migration towards biologically relevant RA synovial fluid, p21(-/-) FLS display a marked increase (3.1-fold; p < 0.05) in migration compared to WT cells. Moreover, this effect is independent of the cell cycle since chemical inhibitors that block the cell cycle have no effect on migration. In contrast, p21 is required to repress migration as restoration of p21 expression in p21(-/-) FLS reverses this effect. Taken together, these data suggest that p21 plays a novel role in normal FLS, namely to repress migration. Loss of p21 expression that occurs in RA FLS may contribute to excessive invasion and subsequent joint destruction.