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ID PMID Title PublicationDate abstract
18830734 Endothelial nitric oxide synthase T-786C polymorphism in rheumatoid arthritis: association 2009 Feb Several genetic factors were implicated in the pathogenesis of rheumatoid arthritis (RA). A case-control study was carried out to verify the associations of T-786C polymorphism in the promoter region of the endothelial nitric oxide synthase (eNOS) gene with RA. One hundred and five consecutive RA patients and 100 healthy controls were genotyped. The distribution of the T-786C genotype and alleles did not differ significantly between RA patients and controls. Nevertheless, the frequency of extraarticular manifestations was significantly greater among the carriers of the C/C genotype than among carriers of the T/C and T/T genotypes (P = 0.022). The C/C genotype was significantly associated with extraarticular manifestations compared with the T/T and T/C genotypes taken together (OR = 4.9, 95% CI = 1.3-18.9). The C allele was significantly associated with extraarticular manifestations of RA (P(corr) = 0.032). The results suggested the existence of an association between the T-786C polymorphism of the eNOS gene and extraarticular manifestations of RA.
17122006 Distribution of Mycoplasma pneumoniae and Mycoplasma salivarium in the synovial fluid of a 2007 Mar By use of a very sensitive nested PCR method targeting part of the strongly conserved mycoplasmal 16S RNA genes, Mycoplasma pneumoniae was found in the synovial fluid of 19/24 (79%) of rheumatoid arthritis patients, 6/6 (100%) of patients with nonrheumatoid inflammatory arthritis, and 8/10 (80%) of osteoarthritis patients attending the rheumatology clinic for drainage of joint effusions. It was not found in the synovial exudates of 13 people attending the orthopedic clinic with traumatic knee injuries or undergoing surgery for knee replacement. However, M. pneumoniae was detected in 2/4 synovial biopsy specimens from orthopedic patients with traumatic knee injuries. M. pneumoniae was associated with the increased synovial fluids found in arthritic flares but was not found in the synovial fluids of trauma patients. Mycoplasma salivarium occurred sporadically. Mycoplasma fermentans had previously been isolated from patients with inflammatory cellular infiltrates, such as rheumatoid arthritis, but it was not detected for osteoarthritic patients from either clinic. It is possible that these organisms may contribute to chronic inflammation within the joints.
19054829 Elevated synovial expression of triggering receptor expressed on myeloid cells 1 in patien 2009 Nov OBJECTIVE: To determine whether synovial expression of triggering receptor expressed on myeloid cells 1 (TREM-1) is upregulated in patients with distinct types of inflammatory or non-inflammatory arthritis. METHODS: Synovial fluid (SF) samples were analysed for levels of soluble TREM-1 (sTREM; n = 132), tumour necrosis factor alpha (TNFalpha, n = 78) and leucocyte TREM-1 messenger RNA (n = 48). Synovial tissue from four rheumatoid arthritis (RA) patients, two patients with Crohn's-associated arthritis, one patient with ankylosing spondylitis and one patient with osteoarthritis were examined for TREM-1 expression by immunohistology, and three of the RA samples were also analysed by Western blotting. RESULTS: Synovial fluid sTREM-1 levels in septic arthritis and RA were similar to each other and were each greater than those in gouty arthritis, non-septic/non-RA inflammatory arthritis and non-inflammatory arthritis. Synovial fluid TNFalpha and sTREM-1 levels correlated with each other, and sTREM-1 and leucocyte TREM-1 mRNA levels each correlated with SF leucocyte counts. TREM-1 in RA was expressed in situ in synovial tissue by cells of myelomonocytic lineage but was not detectably expressed in control osteoarthritis synovial tissue. CONCLUSIONS: Synovial TREM-1 expression is increased in septic arthritis and RA. In patients with acute inflammatory arthritis, elevated SF sTREM-1 levels may point the clinician to a diagnosis of septic arthritis or RA. In RA patients, targeting TREM-1 may have therapeutic benefits by reducing local proinflammatory cytokine and chemokine release.
18061474 The expression of IL-20 and IL-24 and their shared receptors are increased in rheumatoid a 2008 Jan The purpose of this study was to analyze the expression of the two proinflammatory cytokines IL-20 and IL-24 and their shared receptors in rheumatoid arthritis and spondyloarthropathy. IL-20 was increased in plasma of rheumatoid arthritis patients compared with osteoarthritis patients and IL-24 was increased in synovial fluid and plasma of rheumatoid arthritis and spondyloarthropathy patients compared with osteoarthritis patients. IL-20 and IL-24 mRNA was only present at low levels in the synovium. In the synovial membrane, IL-20 protein was present in mononuclear cells and neutrophil granulocytes whereas IL-24 protein was observed in endothelial cells and mononuclear cells. IL-20 receptor type 1 and IL-22 receptor were expressed by granulocytes in the synovial fluid. In synovial fluid mononuclear cell cultures, stimulation with recombinant human IL-20 or recombinant human IL-24 induced monocyte chemoattractant protein 1 (CCL2/MCP-1) secretion, but not tumour necrosis factor alpha mRNA synthesis or IL-6 secretion. Both IL-20 and IL-24 showed correlations to CCL2/MCP-1 in plasma from rheumatoid arthritis and spondyloarthropathy patients. This study associates IL-20 and IL-24 to the synovium of rheumatoid arthritis and spondyloarthropathy and results indicate that the two cytokines contribute to disease pathogenesis through recruitment of neutrophil granulocytes and induction of CCL2/MCP-1.
18613836 Understanding the mechanistic basis in rheumatoid arthritis for clinical response to anti- 2008 Jun With the clinical introduction of the anti-CD20 antibody rituximab for the treatment of rheumatoid arthritis (RA), B-cell-targeted therapy has become an accepted strategy for the treatment of a common chronic inflammatory disease. From recently reported synovial biopsy studies, we can begin to develop a pathophysiologic model of the sequential synovial cellular and molecular changes induced by rituximab infusions. These findings may explain how the rapid and early depletion of CD20-bearing B cells may later lead to the more far-reaching histopathologic changes that are associated with clinical responsiveness. Anti-CD20 antibody treatments may therefore affect the representation of not only mature B lymphocytes and differentiated immunoglobulin-secreting cells but also infiltrating cells such as synovial macrophages and fibroblast-like synoviocytes. In light of the known prominence of recirculating memory B cells in RA pathogenesis, we propose that clinical efficacy also in part reflects the development of an effective blockade of the recirculation of potentially pathologic B cells that may prevent reseeding of pathologic synovial ectopic lymphoid tissues.
16646978 The new IL-1 family member IL-1F8 stimulates production of inflammatory mediators by synov 2006 Six novel members of the IL-1 family of cytokines were recently identified, primarily through the use of DNA database searches for IL-1 homologues, and were named IL-1F5 to IL-1F10. In the present study, we investigated the effect of IL-1F8 on primary human joint cells, and examined the expression of the new IL-1 family members in human and mouse joints. Human synovial fibroblasts (hSFs) and human articular chondrocytes (hACs) expressed the IL-1F8 receptor (IL-1Rrp2) and produced pro-inflammatory mediators in response to recombinant IL-1F8. IL-1F8 mRNA expression was increased in hSFs upon stimulation with proinflammatory cytokines, whereas in hACs IL-1F8 mRNA expression was constitutive. However, IL-1F8 protein was undetectable in hSF and hAC culture supernatants. Furthermore, although IL-1beta protein levels were increased in inflamed human and mouse joint tissue, IL-1F8 protein levels were not. IL-1F8 levels in synovial fluids were similar to or lower than those in matched serum samples, suggesting that the joint itself is not a major source of IL-1F8. Serum levels of IL-1F8 were similar in healthy donors, and patients with rheumatoid arthritis, osteoarthritis and septic shock, and did not correlate with inflammatory status. Interestingly however, we observed high IL-1F8 levels in several serum samples in all groups. In conclusion, IL-1F8 exerts proinflammatory effects in primary human joint cells. Joint and serum IL-1F8 protein levels did not correlate with inflammation, but they were high in some human serum samples tested, including samples from patients with rheumatoid arthritis. It remains to be determined whether circulating IL-1F8 can contribute to joint inflammation in rheumatoid arthritis.
18843785 Putative role of functional interferon regulatory factor 5 (IRF5) polymorphism in rheumato 2008 Nov OBJECTIVE: .Recent studies suggest that polymorphisms of interferon regulatory factor 5 (IRF5) are significantly associated with systemic lupus erythematosus in several populations. The effect of IRF5 polymorphism on susceptibility to rheumatoid arthritis (RA) has been investigated, and the results were inconsistent. We analyzed the genetic effects of IRF5 polymorphisms on RA in a Korean population. METHODS: Eight single-nucleotide polymorphisms (SNP) and 2 insertion-deletion polymorphisms in IRF5 were genotyped in 2183 subjects (1204 RA cases and 979 controls) using the TaqMan(R) method. The genetic effects of SNP on the risk of RA were evaluated using chi-square tests and multivariate logistic regression, controlling for age, sex, and shared epitope (SE), and we then performed conditional analysis by SE status and anti-cyclic citrullinated peptide (anti-CCP) antibody (Ab) status. Data from a Mantel-Haenszel metaanalysis of odds ratios (OR) were subsequently combined in a separate analysis with the results of the association of rs2004640 with RA from a previous study. RESULTS: Two of the IRF5 polymorphisms, CGGGGindel (OR 1.38, 95% CI 1.09-1.76, pcorr = 0.04) and rs2004640 (OR 1.36, 95% CI 1.09-1.68, pcorr = 0.03), and one haplotype, including the rs2004640 and the CGGGGindel, ht3 (A-Del-T-C-del-A-T) (OR 1.39, 95% CI 1.09-1.79, pcorr = 0.04) were significantly associated with an increased risk of RA. After stratification according to anti-CCP Ab and SE status, rs2004640 SNP was associated with the anti-CCP Ab-positive (OR 1.47, 95% CI 1.15-1.88, pcorr = 0.01) or SE-positive group (OR 1.54, 95% CI 1.14-2.09, pcorr = 0.03). A combined analysis including all 3 independent cohorts from the previous study revealed an association of the rs2004640 with RA (pooled OR 1.21, 95% CI 1.07-1.38, pooled p = 0.0031 in dominant model). CONCLUSION: Our results suggest that the IRF5 polymorphism is associated with genetic susceptibility to RA at least in a Korean population, and that it may contribute to disease susceptibility in SE-positive or anti-CCP Ab-positive patients with RA.
17467812 Human rheumatoid synovial fibroblasts promote osteoclastogenic activity by activating RANK 2007 May 15 The interplay between the innate immune system and inflammatory bone destruction in the joints of individuals with rheumatoid arthritis (RA) remains unclear. This study was undertaken to explore the effect of toll-like receptor (TLR) signaling in fibroblast-like synoviocytes (FLS) on the expression of RANKL and induction of osteoclastogenic activity. The levels of RANKL mRNA and protein were measured using RT-PCR, real-time PCR, and immunostaining. Monocytes were cocultured with RA -FLS that had been stimulated with TLR ligands in fresh media and subsequently stained for tartrate-resistant acid phosphatase (TRAP) activity. Osteoclast molecule markers were measured using real-time PCR. Expression of TLR-2 and TLR-4 was higher in RA-FLS than in OA-FLS and normal skin fibroblasts. TLR-2 and TLR-4 ligands induced RANKL expression in RA-FLS. TLR stimulation of RA-FLS also induced the production of IL-1beta and TNF-alpha to a lesser extent; however, it had no effect on IL-17 production. Inhibition of TLR induced IL-1beta production, which partially reversed the upregulation of RANKL induced by TLR ligands. RA-FLS stimulated by TLR-2 and TLR-4 ligands and cocultured with human monocytes induced high levels of expression of TRAP, RANK, cathepsin K, calcitonin receptor, and matrix metalloproteinase-9, suggesting that RA-FLS promote osteoclast differentiation. Our results suggest that the TLR signaling pathway, through TLR-2 and TLR-4, induces RANKL expression in RA-FLS and the expression of RANKL promotes the differentiation of osteoclasts in RA synovium. Targeting specific TLRs may be a promising approach to prevent inflammatory bone destruction in the pathogenesis of RA.
17169159 Utility of the Framingham risk score to predict the presence of coronary atherosclerosis i 2006 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.
18657665 Tumor necrosis factor-alpha antagonist use and heart failure in elderly patients with rheu 2008 Aug BACKGROUND: Clinical trials have shown that tumor necrosis factor-alpha antagonists (TNFAs) confer little benefit, and some may cause potential harm in advanced heart failure (HF). Although TNFAs had significant benefits in treating rheumatoid arthritis (RA), little is known whether the drugs pose an increased risk of HF in older patients with RA. METHODS: A cohort study was conducted using data from Medicare and drug benefit programs in 2 states (1994-2004). We identified patients with RA aged > or =65 who received TNFA or methotrexate (MTX). The cohort was divided into patients with and without previous HF. We considered demographic variables, cardiovascular risk factors, RA severity-related measures, and other comorbidities. The primary end point was hospitalization with HF. We used stratified Cox proportional hazards regression to estimate the adjusted effect of TNFAs on HF hospitalization. RESULTS: The cohort consisted of 1,002 TNFA users and 5,593 MTX users. There were 59 HF admissions during 1,680 person-years of TNFA use and 227 HF admissions during 10,623 person-years of MTX use. Comparing TNFA with MTX users, the adjusted hazard ratio for HF hospitalization was 1.70 (95% confidence interval 1.07-2.69). We found similar results in patients with and without previous HF. Among patients with previous HF, the adjusted hazard ratio for death was 4.19 (95% confidence interval 1.48-11.89). CONCLUSIONS: TNFAs may increase the risk of both first hospitalization and exacerbation of HF in elderly patients with RA. The potential for residual confounding in our study cannot be ruled out; larger and more detailed studies are needed to confirm the findings.
18230627 The effectiveness of leflunomide as a co-therapy of tumour necrosis factor inhibitors in r 2009 Jan BACKGROUND: Randomised trials have demonstrated that the efficacy of anti-tumour necrosis factor (TNF) agents is significantly increased by concomitant methotrexate (MTX) in rheumatoid arthritis (RA). In clinical routine, anti-TNF agents are commonly prescribed with other disease-modifying antirheumatic drugs (DMARDs) than MTX, however their effectiveness in combination with anti-TNF agents is not well established. OBJECTIVE: To compare the effectiveness of leflunomide (LEF) and other conventional DMARDs with MTX as co-therapy to anti-TNF agents in RA. METHODS: All patients on anti-TNF agents and conventional DMARDs within the Swiss Clinical Quality Management (SCQM)-RA database were included (n = 1218) and categorised according to the type of co-therapy into anti-TNF+MTX (n = 842), anti-TNF+LEF (n = 260) and anti-TNF+other DMARDs (n = 116). Drug discontinuation rates and incidence of toxic side effects were analysed using Cox proportional hazard models. Progression of radiographic damage, the evolution of functional disability and the improvement of RA disease activity were analysed using longitudinal regression models, adjusting for potential confounders. RESULTS: The overall discontinuation rates of anti-TNF and conventional DMARD combination therapies were relatively high with a median survival of only 16 months (interquartile range (IQR): 10-37), but they did not differ between the three regimens (p = 0.69). The progression of radiographic damage (p = 0.77), functional disability (p = 0.09) and RA disease activity (p = 0.33) were also similar between the different regimen. In addition, no significant difference in the frequency of adverse events emerged. CONCLUSION: Overall these results suggest that LEF and potentially other conventional DMARDs offer an effective and safe alternative to MTX as co-therapy in combination with anti-TNF agents.
18344017 Off-target activity of TNF-alpha inhibitors characterized by protein biochips. 2008 Jul Tumor necrosis factor-alpha inhibitors are widely and successfully used to treat rheumatic diseases. However, significant side effects have been reported. To detect the potential off-target activities of such inhibitors we characterized two therapeutic antibodies (adalimumab, infliximab) and one receptor fusion protein (etanercept) on protein biochips (UNIchip AV-400) containing a printed serial dilution of tumor necrosis factor-alpha and about 384 different human proteins. Etanercept binds to ten proteins (affinity: 20-33% of tumor necrosis factor-alpha recognition), and six of these proteins are related to ribosomal proteins. Interestingly, adalimumab binds to the same six proteins related to ribosomal proteins (affinity: 12-18%) as well as to four proteins crucially involved in ribosomal protein synthesis. Alignment of protein sequences indicates no significant sequence homology between these ten proteins bound by the biological drugs with the highest off-target activities. Taken together, our in vitro results demonstrate that a significant number of proteins are recognized by tumor necrosis factor-alpha inhibitors and are related to ribosome biogenesis.
17977488 Safety of T-cell co-stimulation modulation with abatacept in patients with rheumatoid arth 2007 Sep Abatacept selectively modulates the CD80/CD86:CD28 co-stimulatory signal required for full T-cell activation, and has been approved for the treatment of rheumatoid arthritis (RA) in combination with methotrexate in a number of countries, including the United States, Canada, and the European Union. As with any new agent, it is important to assess the safety and tolerability of abatacept, and hence an integrated safety analysis of five randomized, placebo-controlled, double-blind core abatacept clinical trials was performed. The 2,944 patients enrolled had active RA and were receiving a variety of biologic and non-biologic background disease-modifying antirheumatic drugs. Overall, 1,955 patients were treated with abatacept during the double-blind periods, and 2,688 during the cumulative double-blind and open-label periods (yielding 4764 patient-years of exposure in total). Overall frequencies of adverse events (AEs; 88.8% vs. 85.1%), serious AEs (SAEs14.0% vs. 12.5%) and malignancies (1.4% vs. 1.1%) were similar in abatacept- versus placebo-treated patients, respectively (regardless of the potential relationship to the study therapy). Discontinuations due to SAEs were 2.8% in the abatacept group vs. 1.6% in the placebo group. The frequency of serious infections was low overall (3.0% vs. 1.9% in abatacept- versus placebo-treated patients, respectively). Acute infusional AEs (9.8% vs. 6.7% in the abatacept versus placebo groups, respectively) were mostly mild-to-moderate in intensity. Safety data through cumulative exposure were consistent with those from the double-blind periods; there was no evidence of an increase in the incidence of serious infections or malignancies with increasing exposure to abatacept. Abatacept was associated with low levels of immunogenicity, with no detectable association between immunogenicity and safety or efficacy. Abatacept treatment did not result in a higher rate of seroconversion for anti-nuclear or anti-dsDNA antibodies versus placebo, and was associated with a similar frequency of autoimmune events versus placebo (1.4% vs. 1.8%, respectively). Moreover, treatment with abatacept may not markedly impair the response to vaccination in healthy volunteers or RA patients. Overall, these findings suggest that abatacept has acceptable safety and tolerability in patients with RA. Ongoing follow-up will monitor whether these features are maintained over long-term abatacept use.
16837489 Etanercept maintains the clinical benefit achieved by infliximab in patients with rheumato 2007 Feb OBJECTIVE: To evaluate the efficacy of switching to etanercept treatment in patients with rheumatoid arthritis who already responded to infliximab, but presented side effects. METHODS: Charts of 553 patients with rheumatoid arthritis were retrospectively reviewed to select patients who responded to the treatment with infliximab and switched to etanercept because of occurrence of adverse effects. Clinical data were gathered during 24 weeks of etanercept treatment and for the same period of infliximab treatment before infliximab was stopped. Disease Activity Score computed on 44 joints (DAS-44), erythrocyte sedimentation rate (ESR) 1st hour, Visual Analogue Scale (VAS) of pain, Health Assessment Questionnaire (HAQ), and C reactive protein (CRP) were assessed every 8 weeks. RESULTS: 37 patients were analysed. Adverse events to infliximab were mostly infusion reactions. No statistically significant difference between infliximab, before withdrawal, and etanercept, after 24 weeks, was detected in terms of DAS-44 (2.7 and 1.9, respectively), HAQ (0.75 and 0.75, respectively), ESR (21 and 14, respectively) and CRP (0.5 and 0.3, respectively). VAS pain decreased significantly after switching to etanercept treatment (40 and 24, respectively; p<0.05). CONCLUSIONS: Our study shows that etanercept maintains the clinical benefit achieved by infliximab, and suggests that a second tumour necrosis factor (TNF) alpha inhibitor can be the favourable treatment for rheumatoid arthritis when the first TNFalpha blocker has been withdrawn because of adverse events.
19169303 [Corneal manifestations in systemic diseases]. 2008 Systemic diseases affecting the cornea have a wide range of manifestations. The detailed study of all pathologies that cause corneal alteration is unapproachable, so we have centered our interest in the most prevalent or characteristic of them. In this paper we have divided these pathologies in sections to facilitate their study. Pulmonar and conective tissue (like colagen, rheumatologic and idiopathic inflamatory diseases), dermatologic, cardiovascular, hematologic, digestive and hepatopancreatic diseases with corneal alteration are described. Endocrine and metabolic diseases, malnutrition and carential states are also studied, as well as some otorhinolaryngologic and genetic diseases that affect the cornea. Finally, a brief report of ocular toxicity induced by drugs is referred.
16932953 The effect of 3435C>T MDR1 gene polymorphism on rheumatoid arthritis treatment with diseas 2006 Nov OBJECTIVE: Rheumatoid arthritis (RA) is a multifactorial disease, with immunological, genetical as well as environmental factors being implicated in its pathogenesis. Treatment of RA is based mainly on drugs modulating the course of the disease, e.g. methotrexate (MTX) or sulfasalazine (SL). The MDR1 gene product, P-glycoprotein (P-gp), is probably one of the most important and best defined transporters for drug delivery in humans. P-gp transports a wide range of substrates with diverse chemical structures, among them anticancer agents, cardiac drugs, and immunosuppressants. The aim of this study was to examine the effect of the 3435C>T MDR1 gene polymorphism on the efficacy of RA treatment with disease-modifying antirheumatic drugs, i.e. MTX plus methylprednisolone (MP), and SL. METHODS: The study was carried out on 255 patients with RA treated according to two regimes: (1) MTX (7.5-15.0 mg weekly) plus low doses of MP (n=174), (2) SL (1.5-3 g daily, n=81). RESULTS: The probability of remission of RA symptoms after MTX plus MP therapy was 4.65-fold higher in carriers of the TT genotype compared to patients with CC genotype (P=0.003, OR 4.65, 95%CI 1.66-13.05), whereas the probability of remission of RA symptoms in patients treated with SL was 2-fold higher in carriers of TT genotype compared to patients with CC genotype, but did not reach statistical significance (P=0.358, OR=2.00 95% CI=0.58-6.87). CONCLUSION: The results from the present study suggest that the 3435C>T MDR1 gene polymorphism may influence the efficacy of RA therapy with disease-modifying antirheumatic drugs.
16463412 Synovial fluid levels of anti-cyclic citrullinated peptide antibodies and IgA rheumatoid f 2006 Feb 15 OBJECTIVE: To assess the levels of anti-cyclic citrullinated peptide (anti-CCP) and IgA rheumatoid factor (IgA-RF) in synovial fluids of patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and osteoarthritis (OA). METHODS: Knee effusions of 29 patients with RA (23 women, 6 men; mean +/- SD age 60 +/- 15 years), 20 with PsA (6 women, 14 men; mean age 51 +/- 12 years), and 19 with OA (9 women, 10 men; mean age 73 +/- 11.8 years) were aspirated, tested for white blood cell (WBC) counts, centrifuged, and stored at -20 degrees . Sera of 22, 11, and 12 of these patients with RA, PsA, and OA, respectively, were similarly stored. IgG anti-CCP and IgA-RF were detected by enzyme-linked immunosorbent assay. Erythrocyte sedimentation rate and C-reactive protein levels were used as measures of disease activity. RESULTS: Mean levels of synovial fluid anti-CCP and IgA-RF were significantly increased in RA joint effusions compared with PsA and OA (anti-CCP: 150 +/- 134, 34 +/- 29, and 24 +/- 26 units, respectively [P < 0.003]; IgA-RF: 76 +/- 77, 15.7 +/- 10, and 18 +/- 20 units, respectively). No significant difference was noted between OA and PsA. A significant correlation was found between synovial fluid anti-CCP and serum anti-CCP and IgA-RF. In patients with RA, a significant correlation was found between synovial fluid WBC counts and IgA-RF (P = 0.03) and serum IgA-RF (P = 0.008), but not between synovial fluid and serum anti-CCP levels. In RA patients, C-reactive protein correlated with serum IgA-RF. CONCLUSION: Anti-CCP and IgA-RF were significantly increased in synovial fluid of RA in comparison with PsA and OA patients.
18785316 Differential response of the rheumatoid factor and anticitrullinated protein antibodies du 2008 Oct OBJECTIVE: To investigate the effect of anti-tumor necrosis factor (TNF) treatment on rheumatoid factor (IgM-RF) and anticitrullinated protein antibodies (ACPA) and its association with treatment response and acute-phase reactants. METHODS: In a cohort of 188 consecutive patients with rheumatoid arthritis (RA) treated with adalimumab, baseline IgM-RF and ACPA were determined by ELISA, and compared to levels after 28 weeks of treatment. ACPA were measured as antibodies to cyclic citrullinated peptide (anti-CCP). The relative change of antibody levels was correlated to the European League Against Rheumatism response criteria and to the change in acute-phase reactants [erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)]. RESULTS: The median decline in IgM-RF levels was greater than the decline in ACPA levels (31% vs 8%; p<0.001). The decrease in antibody levels was greater in the group of good responders than in the group of nonresponders [43% vs 7% for IgM-RF (p<0.0001) and 16 vs -4% for ACPA (p=0.03)]. Seventeen percent of IgM-RF-positive patients at baseline turned negative at 28 weeks; this qualitative effect was not observed for ACPA. Further, the decline in IgM-RF, but not ACPA, was associated with a decrease in CRP and ESR (p=0.004 and p=0.006, respectively). CONCLUSION: TNF treatment directly influences IgM-RF and ACPA levels, but in those responding to treatment only. The effect on IgM-RF levels and positivity status is greater than on ACPA levels and is associated with the decline in markers of inflammation. These results further emphasize the differential role these autoantibodies may play in RA; IgM-RF as marker of inflammatory activity, and ACPA as qualitatively stable hallmark of RA.
16754627 Ages of onset suggestive of genetic anticipation in rheumatoid arthritis multicase sibship 2007 Jan OBJECTIVES: Previous work has suggested that features of genetic anticipation might be present in familial rheumatoid arthritis (RA), but bias is difficult to exclude when looking at disease in two consecutive generations. We used data from the North American Rheumatoid Arthritis Consortium (NARAC) and the Arthritis Research Campaign National repository for RA multicase pedigrees to determine whether differences in age of onset within multicase sibships were supportive of genetic anticipation. METHOD: RA sibling pairs were identified from both data sets. The period of observation was defined as the time between the first sibling developing RA and the time that the sibship was ascertained for the study. A paired t-test for the difference in ages of RA onset within the pairs was calculated. Ages of conception of the parent were correlated with the age of RA onset. RESULTS: Information was available for 743 sibships in the NARAC data set and 396 sibships in the Arthritis Research Campaign (ARC) data set. In both data sets, the older siblings had an older age of onset than their younger siblings (39.3 vs 36.9 in the NARAC, and 43.8 vs 40.1 in the ARC data set, both P < 0.001). The two data sets were then stratified into tertiles by a period of observation. In both data sets, there was a progressive decline in the sibling age of onset differences. For the first tertile (shortest observation period), the older sibling had a significantly older age of onset than the younger. This difference decreased in the second tertile, and was not significant in the third tertile (longest observation period). There was no significant correlation between the age of RA onset and the maternal or paternal ages of conception in either data set. CONCLUSION: Features compatible with genetic anticipation in RA multicase sibships are subject to observational bias. This does not support a role for genetic anticipation in familial RA.
17690541 Optimized system design and construction of a compact whole-hand scanner for diagnosis of 2007 We have developed a compact magnetic resonance (MR) imaging scanner with permanent magnet, gradient coil set, and radiofrequency (RF) coils optimized for whole-hand examination for the diagnosis of rheumatoid arthritis (RA). The system weighs about 600 kg, and installation space is 2 m(2), excluding the shield room. Hand examinations of normal volunteers and patients with RA were performed using a 3D T(1)-weighted gradient-echo (GRE) sequence and short T(I) inversion recovery 3D fast spin-echo (STIR-3DFSE) sequence, and anatomical structures and various lesions of the hand caused by RA were clearly visualized in a 16-min examination. It was concluded that the system could be used for diagnosis of RA in even a small clinic.