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ID PMID Title PublicationDate abstract
18396440 Prolylcarboxypeptidase: a cardioprotective enzyme. 2009 Mar Prolylcarboxypeptidase (PRCP) is involved in regulating the blood flow through active tissues in order to preserve the internal environment. The expression of PRCP in tissues is determined by a number of pharmacological stimuli such as glucocorticoids and a combination of dexamethasone plus the mu-opioid receptor agonist [D-Ala2, N-Me-Phe4, Gly5-ol]-Enkephalin acetate. PRCP is an enzyme which is associated with preeclampsia, rheumatoid arthritis, and tonsillitis. The interplay between inward cellular signalling required for induced and basal transcription, and PRCP expression have not been mechanistically characterized. Molecules modulated by PRCP include angiotensin II (Ang II), angiotensin III (Ang III), alpha-MSH, and prekallikrein (PK), demonstrating its cardiovascular protective role. In addition to regulating vascular tone, PRCP may modulate proliferation, cell migration, and angiogenesis through regulating angiotensin molecules--and bradykinin--induced endothelium activation. The anti-hypertensive and proinflammatory properties of PRCP implicate that this enzyme may well be an accessible target for anti-inflammatory therapy.
17012290 Role of the MHC2TA gene in autoimmune diseases. 2007 Mar OBJECTIVES: Expression of major histocompatibility complex (MHC) class II genes is almost exclusively regulated by the class II transactivator. A promoter polymorphism (-168A/G, rs3087456) in the MHC2TA gene was associated with increased susceptibility to rheumatoid arthritis, multiple sclerosis and myocardial infarction in a northern European population. However, no evidence of association of this MHC2TA variant with the two autoimmune diseases could be subsequently detected in independent cohorts. AIM: To test the aforementioned single nucleotide polymorphism and another G-->C change (nt1614 from coding sequence, rs4774) to analyse the haplotype pattern in this MHC2TA gene. METHODS: A case-control study was performed with 350 patients with rheumatoid arthritis, 396 patients with multiple sclerosis, 663 patients with inflammatory bowel disease (IBD) and 519 healthy controls from Madrid. Genotyping was ascertained by using TaqMan assays-on-demand on a 7900HT analyser, following the manufacturer's suggestions (Applied Biosystems, Foster City, California, USA). Haplotypes were inferred with the expectation-maximisation algorithm implemented by the Arlequin software. RESULTS: No independent association with these autoimmune diseases was found for either polymorphism in the Spanish cohorts tested. However, when haplotypes were compared between patients with rheumatoid arthritis and controls, a significant difference in their overall frequency distribution was observed, evidencing a protective haplotype (-168A/1614C, p = 0.006; odds ratio (OR) 0.7) and a risk haplotype (-168G/1614C, p = 0.019; OR 1.6). Patients with multiple sclerosis mirrored these results, but no effect on IBD was identified. CONCLUSIONS: The MHC2TA gene influences predisposition to rheumatoid arthritis and multiple sclerosis, but not to IBD. The -168G allele is not an aetiological variant in itself, but a genetic marker of susceptibility/protection haplotypes.
16540076 Specific modification of peptide-bound citrulline residues. 2006 May 1 Immune reactions to citrulline-containing proteins appear to be central in the immunopathogenesis of rheumatoid arthritis. Citrulline residues are introduced into proteins by deimination of arginine residues, likely by an enzymatic process. There is a need to characterize which proteins in the inflamed joints of rheumatoid patients contain citrulline in situ. The characterization of deiminated proteins will be greatly facilitated by specific modification of peptide-bound citrulline residues that will enable specific enrichment and detection of citrulline-containing peptides. This study presents the details of such a modification method. The chemistry behind the reaction of the ureido group of citrulline with 2,3-butanedione in the presence of antipyrine is unraveled. Parameters for optimization of the reaction with respect to specificity and completeness, including the testing of different acids, reactant concentrations, and reaction time, are presented. This modification reaction is specific for citrulline residues. The modified product shows a characteristic mass shift of +238Da, as demonstrated by mass spectrometry. The product absorbs UV-Vis radiation at 464nm, and it is demonstrated that this can be used to selectively monitor citrulline-containing peptides during the separation of protein digests. Finally, the structure of the product of modified citrulline is solved by nuclear magnetic resonance spectroscopy using N-butylurea as a model substance. The results presented should facilitate the development of tags that can be used for the enrichment and subsequent detection of citrulline-containing protein fragments by mass spectrometry.
19004047 Association between the aggrecan gene and rheumatoid arthritis. 2008 Dec OBJECTIVE: Genetic and environmental factors seem to be involved in the onset of rheumatoid arthritis (RA). We analyzed whether a variable number of tandem repeats (VNTR) polymorphism in the aggrecan gene was associated to RA. METHODS: The study population comprised 170 European-derived Brazilian patients with diagnosis of RA. The control group comprised 148 European-derived Brazilian healthy blood donors. The aggrecan VNTR polymorphism was genotyped by DNA amplification by polymerase chain reaction, followed by electrophoresis in polyacrylamide gel. RESULTS: There was a statistically significant higher frequency of alleles of shorter length in the patient group compared to controls (p = 0.001), suggesting that individuals carrying short alleles are more likely to develop RA. There was no association between short alleles and clinical characteristics of RA. CONCLUSION: Our results provide evidence of an association between the aggrecan gene VNTR polymorphism and RA.
18189189 Differential CCR5Delta32 allelic frequencies in juvenile idiopathic arthritis subtypes: ev 2008 Jan BACKGROUND: Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease of childhood and is characterized by persistent arthritis for at least 6 weeks. Its aetiopathogenesis is unknown but there is strong evidence that there is a substantial genetic component. Chemokine receptors genes are among the candidate genes for association with arthritis and other inflammatory diseases. The CC chemokine receptor 5 (CCR5)Delta32 polymorphism has been associated with rheumatoid arthritis (RA), conferring a protective effect. OBJECTIVE: To determine whether the CCR5Delta32 polymorphism is associated with JIA and RA in Brazilian patients. METHODS: We investigated 203 RA patients, 101 JIA patients, and 104 healthy individuals by amplification of the CCR5Delta32 deletion. We compared the allelic frequencies among these groups, as well as among different JIA subtypes. RESULTS: The frequency of the Delta32 allele was higher in JIA patients (9.4%) as compared to control subjects (3.8%) and RA patients (3.2%). Grouping the patients according to JIA subtypes, we observed a higher CCR5Delta32 allelic frequency in the subtypes with a greater inflammatory component: 4.1% in oligoarticular (n = 49), 11.2% in polyarticular (n = 40) [9.5% in rheumatoid factor negative (RF-) and 33.3% in RF positive (+)], and 25% in systemic JIA (n = 12). CONCLUSIONS: This study suggests that in JIA, unlike in RA, CCR5Delta32 does not have a protective effect, but instead it could be a factor associated with more inflammatory forms of the disease. These observations give rise to new questions about the mechanism and the cellular types involved in JIA as well as about the aetiology of JIA.
18791351 Effects of glucocorticoid treatment on focal and systemic bone loss in rheumatoid arthriti 2008 Jul Rheumatoid arthritis (RA) is characterized by an extensive dysregulation in skeletal homeostasis recognized as 1) focal articular bone erosions, 2) iuxta-articular osteopenia, 3) systemic osteoporosis (OP) and fractures, as is well documented in both cross-sectional and prospective studies. The disease activity, as a consequence of new insights into the complex interaction between bone cells and a variety of cells of the immune system, has emerged as the main responsible for both focal and systemic bone loss. Given this background, the therapeutic approach to RA has become more aggressive, and a more widespread use of low-dose glucocorticoids (GC), recently categorized as disease modifying antirheumatic drugs (DMARD) because of their additional joint sparing effect on the long-term, has also been recommended from the early stages. Addressing the effects of GC on systemic bone loss in RA, GC are considered, in addition to inflammation and inactivity, the major risk factors for OP and fractures. As a consequence, among the most recent recommendations (i.e. dosing, timing, and tapering strategies) for patients receiving GC for more than 3 months, prevention and treatment of GC-induced OP (i.e. calcium, vitamin D, and bisphosphonates) are included. However, innovative GC, characterized by a more favorable risk/benefit profile such as selective GC receptor agonists (SEGRA), are currently in the pipeline. This article reviews the major points of evidence so far available, regarding the effects of GC on focal and systemic bone loss.
17266570 Development of low molecular weight CXCR4 antagonists by exploratory structural tuning of 2007 The chemokine receptor, CXCR4, is a GPCR that transduces signals of its endogenous ligand, CXCL12 (stromal cell-derived factor-1, SDF-1). The CXCL12-CXCR4 system plays an important role in the migration of progenitors during embryologic development of the cardiovascular, hemopoietic, central nervous systems, etc. This system has recently been proven to be involved in several problematic diseases, including HIV infection, cancer cell metastasis, leukemia cell progression, rheumatoid arthritis (RA) and pulmonary fibrosis. Thus, CXCR4 is thought to be an important therapeutic target to overcome the above diseases. Fourteen-mer peptides, T140 and its analogs, were previously found to be specific CXCR4 antagonists that were characterized as HIV-entry inhibitors, anti-cancer-metastatic agents, anti-chronic lymphocytic/acute lymphoblastic leukemia agents and anti-RA agents. Based on our knowledge of pharmacophores of T140, CXCR4 antagonists, such as FC131, were previously found by the efficient utilization of cyclic pentapeptide libraries. This review article focuses on our recent research on the development of low molecular weight CXCR4 antagonists including FC131 analogs, in which structural tuning of the cyclic peptide ring and chemical modifications were performed for an increase in potency and a reduction of the peptide character.
17875183 Variant mannose-binding lectin 2 genotype is a risk factor for reactive systemic amyloidos 2007 Oct OBJECTIVE: The aim of this study was to investigate whether polymorphism of the mannose-binding lectin 2 (MBL2) gene is related to the occurrence of systemic AA amyloidosis in patients with rheumatoid arthritis (RA). METHODS: MBL2 structural gene polymorphisms at codon 52 (CGT-->TGT, Arg-->Cys; D), codon 54 (GGC-->GAC, Gly-->Asp; B) and codon 57 (GGA-->GAA, Gly--> Glu; C), and MBL2 promoter region polymorphism at position -221 (G-->C) were examined in 57 patients with RA complicated by biopsy-proven reactive amyloidosis and 51 control RA patients without amyloid. RESULTS: A strong association was found between the presence of a structural MBL2 gene variant O (B, D or C) and the occurrence of amyloidosis in RA patients: 29 of 57 (50.9%) of the RA patients with amyloid had a variant allele compared with 12 of 51 (23.5%) of the RA patients without amyloid (OR 3.37, 95% CI 1.47-7.72; P = 0.004). CONCLUSION: We conclude that variant MBL2 structural genotype constitutes a significant risk factor for reactive amyloidosis in RA and that the increased risk is probably related to MBL-mediated impairment of mononuclear phagocyte function.
19003601 Chitinase 3-Like-1 (CHI3L1): a putative disease marker at the interface of proteomics and 2008 Chitinase 3-Like-1 (CHI3L1) is a secreted 40 kDa glycoprotein that is upregulated in a number of human cancers and in non-neoplastic disease states characterized by chronic inflammation and tissue remodeling. Increased serum levels of CHI3L1 parallel disease severity, poorer prognosis, and shorter survival in many human neoplasias, including cancers of the breast, colon, prostate, ovaries, brain, thyroid, lung, and liver. Increased serum CHI3L1 also correlates with disease severity in rheumatoid arthritis, osteoarthritis, liver fibrosis, inflammatory bowel disease, and bacterial septicemia. CHI3L1 is a rheumatoid arthritis (RA) autoantigen, and MHC complexes containing specific CHI3L1 peptides have been found in RA patients; however, intranasal introduction of these same CHI3L1 peptides can induce tolerance towards them. CHI3L1 is a nonhydrolytic member of the human chitinase family that binds chitin tightly and heparin at lower affinity. Interactions with type I collagen, CHI3L1's only known protein-binding partner, helps regulate collagen fibril formation. The principal sources of CHI3L1 are activated macrophages and chondrocytes, neutrophils, and some tissue and tumor cells. CHI3L1 can act as a fibroblast mitogen and can activate several signaling pathways, however, no cell surface-binding partner for CHI3L1 has been identified. The ability of CHI3L1 to bind both proteins and carbohydrates allows potential interactions with a variety of cell-surface and extracellular-matrix proteins, proteoglycans, and polysaccharides, and thus CHI3L1 can interface between proteomics and glycomics.
17564711 Etanercept and infliximab induce the same serological autoimmune modifications in patients 2007 Nov Etanercept and infliximab treatments are often associated with autoantibodies induction. Their reported prevalences vary among different studies and the conclusions are somehow conflicting, mainly regarding whether the two drugs induce the same modifications. In this small prospective study, specifically designed to identify transient phenomena, we assess the prevalence of different relevant rheumatologic autoantibodies during anti-TNF-alpha courses in patients with rheumatoid arthritis. We report that both etanercept and infliximab transiently induce anti-DNA antibodies in 50-78% of patients, respectively, and these antibodies seem to be different from the typical lupus associated ones. Antinuclear antibodies (ANA) increased their titres and were newly produced up to 100% of patients. No other relevant antibodies are affected. Finally, as also confirmed for the first time by the patients switched from one drug to the other, the two TNF-alpha blockers behave similarly.
17039310 SAA1 gene polymorphisms and the risk of AA amyloidosis in Japanese patients with rheumatoi 2006 To investigate the precise modality of association between SAA1 gene polymorphisms and the development of AA amyloidosis in patients with rheumatoid arthritis (RA), Japanese patients with RA (n=153), among whom 29 were histologically diagnosed as having amyloidosis, were genotyped for three single nucleotide polymorphisms (SNPs), C-13T, C2995T, and C3010T, in the SAA gene. Pairwise linkage disequilibrium coefficients between each pair of SNPs were calculated and estimated haplotype frequencies were compared between patients with and without amyloidosis. Possible associations between these SNPs and amyloidosis were analyzed by a case-control study and by the Kaplan-Meier method, in which the endpoint was defined as the time of diagnosis of AA amyloidosis. The -13T and 2995C alleles, which were in a tight linkage disequilibrium, were more frequent in the patients with amyloidosis, and the groups with the -13TT and 2995CC genotype had worse survival curves than patients without these genotypes, whereas C3010T was not associated with amyloidosis. Moreover, the haplotype containing -13C and 2995T was found to be protective. Both C-13T and C2995T were associated with the development of amyloidosis. Examining both polymorphisms may be more useful than examining only one of them for estimating the risk of the development of amyloidosis.
18243320 Lactobacillus casei suppresses experimental arthritis by down-regulating T helper 1 effect 2008 May Although the beneficial effects of probiotics on wide variety of diseases have been shown, little is known about how probiotics modulate the immune system. In this study we elucidated the underlying mechanisms how Lactobacillus casei (L. casei) protects against rheumatoid arthritis (RA) progression by investigating the effector functions of CD4(+) T cells. Oral administration of L. casei suppressed collagen-induced arthritis (CIA) and reduced paw swelling, lymphocyte infiltration and destruction of cartilage tissue. L. casei administration reduced type II collagen (CII)-reactive proinflammatory molecules (IL-1beta, IL-2, IL-6, IL-12, IL-17, IFN-gamma, TNF-alpha and Cox-2) by CD4(+) T cells. L. casei administration also reduced translocation of NF-kappaB into nucleus and CII-reactive Th1-type IgG isotypes IgG2a and IgG2b, while up-regulating immunoregulatory IL-10 levels. Our results suggest that oral administration of L. casei suppresses the type II collagen-reactive effector function of Th1-type cellular and humoral immune responses in arthritic inflammation.
18702106 Rheumatoid arthritis, alcohol, leflunomide and methotrexate. Can changes to the BSR guidel 2008 Dec INTRODUCTION: The summary of product characteristics for leflunomide and methotrexate recommend avoiding alcohol. By contrast, the latest British Society for Rheumatology (BSR) guidelines suggest that alcohol should be 'well within national limits'. A postal survey was performed of rheumatoid arthritis (RA) patients to address their alcohol consumption, and assess whether this influenced any rise in alanine transaminase (ALT) levels while on leflunomide or methotrexate. METHODS: RA patients commenced on methotrexate or leflunomide within the preceding two years were identified using the departmental database. A total of 200 patients on methotrexate or leflunomide were sent questionnaires covering demographics, disease details, duration of disease-modifying anti-rheumatic drug (DMARD) use, previous medical and drug history, alcohol advice recalled, and alcohol consumption while on the drug. ALT levels at drug commencement and the highest level on the drug were recorded. RESULTS: Replies were received from 69.5% of methotrexate and 57.5% of leflunomide patients. 68.6% of patients recalled receiving alcohol advice. 55.8% of leflunomide patients did not drink alcohol prior to taking the DMARD, compared with 39.4% of methotrexate patients. 27.7% of leflunomide patients continued to drink alcohol compared with 64.3% on methotrexate. For both drugs, no patterns emerged to suggest that baseline or highest ALT levels were influenced by higher levels of alcohol consumption. DISCUSSION: No differences were found with either methotrexate or leflunomide for self-reported alcohol consumption influencing ALT levels. It is appropriate to give similar alcohol advice to patients beginning therapy with either methotrexate or leflunomide. This research has not found any evidence to contradict the relaxation of advice on alcohol consumption with methotrexate and leflunomide in the updated BSR guidelines.
18052966 Circulating surfactant protein D is decreased in early rheumatoid arthritis: a 1-year pros 2008 Jan Innate immune system abnormalities, e.g., mannan-binding lectin (MBL) genotype variants, have been demonstrated to modify the disease course of rheumatoid arthritis (RA). Surfactant protein D (SP-D) shares important structural and functional properties with MBL suggesting that SP-D may be an additional RA disease modifier. The Met11Thr polymorphism in the N-terminal part of SP-D is an important determinant for the SP-D serum level, but this polymorphism is also essential to the function and assembly into oligomers. We aimed to compare the serum levels of SP-D in a cohort of newly diagnosed untreated RA patients with healthy matched controls, and to investigate if there was an association to core measures of disease activity within the first year after disease onset. Secondly, we aimed to investigate whether the Met11Thr polymorphism was associated with RA. Serum SP-D was significantly lower in DMARD naive RA patients compared with healthy controls (P = 0.016). Median SP-D concentration at inclusion was 878 ng/ml (95% CI: 730-1033) and 1164 ng/ml (95% CI: 1093-1366) in RA patients and matched controls, respectively. SP-D increased during Methotrexate treatment (P < 0.0001), and at 1-year follow-up median SP-D was 1032 ng/ml (95% CI: 777-1255). SP-D levels did not correlate with traditional disease activity measures. The Thr11/Thr11 genotype and the Thr11 allele tended to be more frequent in RA patients. In conclusion, the low serum level of SP-D and the lack of correlation with traditional disease activity measures indicate that SP-D reflects a distinctive aspect in the RA pathogenesis.
18975138 Recurrent pancreatic arteritis and vasculogenic relapsing pancreatitis in rheumatoid arthr 2008 Dec The aim of this study was to determine: the prevalence, and histological characteristics of vasculitis in the pancreas, and to follow the formal pathogenesis of multifocal pancreatitis due to arteritis and/or arteriolitis (multifocal vasculogenic pancreatitis). A randomized autopsy population of 161 in-patients with rheumatoid arthritis (RA) was studied. Systemic vasculitis (SV) complicated RA in 36 (22.36%) of 161 cases; tissue samples of pancreas were available for histologic evaluation in 28 patients. Pancreatitis and vasculitis were characterized histologically and immunohistochemically. Vasculogenic, multifocal pancreatitis was not recognized clinically. Vasculitis of the pancreatic arterioles and small arteries (branches of splenic artery, upper and lower gastroduodenal arteries) can lead to local ischaemia and to regressive changes in the pancreas. This vasculogenic process is more or less widespread and multifocal, depending on the number of involved vessels and is followed by reactive inflammation, depending on the stages of the pathological process. Because of the recurrent nature of vasculitis with time these regressive changes accumulate within the pancreas and may contribute to an unexpected circulatory failure and sudden death of the patient. Vasculogenic microinfarcts in the pancreas may be clinically characterized by unexplained recurrent abdominal symptoms and spontaneous remissions which insidiously may lead to metabolic failure resistant to therapy.
17589850 The association of DRB1*04 share epitope alleles and tumor necrosis factor-alpha gene poly 2007 Dec Rheumatoid arthritis (RA) in Thai population is significantly associated with HLA-DR4 shared epitope (SE) alleles, particularly with DRB1*0405 (P = 0.00004, OR = 3.84, 95% CI = 1.93, 7.7). In addition, tumor necrosis factor-alpha (TNF-alpha) gene -863A alleles were found to be significantly increased in 77 RA patients compared to 162 healthy controls (P = 0.03, OR = 1.73, 95% CI = 1.05, 2.87). Interestingly, TNF-863 AC and SE have a synergistic effect on the susceptibility to RA. The OR for the presence of both risk factors (DR4 SE and -863 AC) was cumulative: 15.4 (95% CI = 3.75, 73.6) while the separate OR of DR4 SE and -863 AC were 3.84 and 2.36, respectively. The TNF was not associated with the clinical manifestation and severity of Thai RA patients. However, a highly significant association was found between RF positivity, one marker for severity, and RA patients with DR4 SE (P = 0.0005, OR = 9.42, 95% CI = 2.26, 45.27).
17468813 Failure to confirm association between PDCD1 polymorphisms and rheumatoid arthritis in a J 2007 Programmed cell death 1 (PDCD1) is a necessary negative regulator to maintain peripheral tolerance and is a key molecule in the development of autoimmune diseases. Although PDCD1 gene polymorphisms and haplotypes were reported to be associated with rheumatoid arthritis (RA), replication studies later on showed conflicting results. Here, we analyzed the association of PDCD1 with RA using a large series of Japanese RA patients and population-based controls. DNA samples were obtained from 1,504 RA patients and 449 sex-matched controls. All samples were genotyped for three SNPs on PDCD1 (PD-1.1, PD-1.3 and PD-1.5) using the TaqMan fluorogenic 5' nuclease assay. Chi-square testing was performed for a case-control study, and the PENHAPLO program was used for haplotype estimation. We could not observe any significant association of PD-1.1 or PD-1.5 polymorphisms between RA. PD-1.3, which was reported to be involved in susceptibility to RA in patients of European descent, was non-polymorphic in the Japanese population. We conclude that polymorphisms in the PDCD1 gene analyzed here are not associated with RA in a Japanese population.
17133560 Isotype distribution of anti-cyclic citrullinated peptide antibodies in undifferentiated a 2006 Dec OBJECTIVE: The evolution of the rheumatoid arthritis (RA)-specific anti-cyclic citrullinated peptide (anti-CCP) antibody response, as measured by the isotypes of anti-CCP, has not been described. This study was undertaken to determine anti-CCP isotype usage in patients with undifferentiated arthritis (UA), patients with recent-onset RA, and patients with RA of long duration. METHODS: IgA, IgM, and IgG subclasses of anti-CCP were measured by enzyme-linked immunosorbent assay in serum samples that were obtained from IgG anti-CCP antibody-positive patients with UA (n = 110) and IgG anti-CCP antibody-positive patients with RA (n = 152) early after the onset of arthritis. Patients with UA in whom RA developed within 1 year (UA-->RA) were compared with patients with UA in whom RA did not develop within 1 year (UA-->UA). In addition, baseline serum samples obtained from a subset of patients with RA (n = 64) were compared with sera obtained from the same patients a median of 7 years later. RESULTS: IgM anti-CCP was present in early samples from both patients with UA and patients with RA and in followup samples from patients with RA. Several IgG anti-CCP antibody-positive patients who did not have IgM anti-CCP early after disease onset did display IgM anti-CCP later in the course of the arthritis. A diverse pattern of isotype usage was detected in early samples, with a trend toward lower frequencies of all isotypes of anti-CCP in patients with UA compared with patients with RA and in UA-->UA patients compared with UA-->RA patients. Levels of all isotypes except IgG1 had decreased after 7 years. CONCLUSION: These data indicate development of the anti-CCP isotype repertoire into full usage early in the course of arthritis. The sustained presence of IgM anti-CCP indicates ongoing recruitment of new B cells into the anti-CCP response, reflecting a continuous (re)activation of the RA-specific anti-CCP response during the course of anti-CCP-positive arthritis.
17039315 Leflunomide-related acute interstitial pneumonia in two patients with rheumatoid arthritis 2006 We describe two cases of leflunomide-related interstitial pneumonia (IP). A 75-year-old woman with rheumatoid arthritis (RA) developed rapidly progressing IP 45 days after institution of leflunomide. She died of respiratory failure, and an autopsy revealed a mixed pattern of acute and organizing diffuse alveolar damage. A 69-year-old woman with RA also developed acute IP 3 months after institution of leflunomide. Methylprednisolone pulse therapy and cholestyramine ameliorated her IP. The implication of leflunomide in the pathogenesis of IP was suggested.
18821671 Induction of osteoclast-associated receptor, a key osteoclast costimulation molecule, in r 2008 Oct OBJECTIVE: Osteoclast-associated receptor (OSCAR) is a newly identified osteoclast-specific receptor and is of key importance in the process of osteoclast costimulation. This study was undertaken to define the role of costimulation in osteoclast differentiation during inflammatory arthritis. METHODS: OSCAR expression was assessed in the synovium and peripheral blood monocytes of patients with rheumatoid arthritis (RA), and associations with disease activity were assessed. Serum levels of OSCAR were determined by enzyme-linked immunosorbent assay. In vitro osteoclast assays were performed to characterize the role of OSCAR in human osteoclastogenesis. Cytokine regulation of OSCAR was investigated by reverse transcriptase-polymerase chain reaction. RESULTS: OSCAR was expressed by osteoclasts at the erosion front and by mononuclear cells around synovial microvessels. Flow cytometry revealed enhanced expression of OSCAR in peripheral blood monocytes of RA patients as compared with healthy controls. OSCAR expression was correlated with disease activity and acute-phase reactant concentrations. Serum levels of soluble OSCAR were lower in RA patients than in healthy controls. Monocytes with high OSCAR expression exhibited an enhanced potential to differentiate into osteoclasts. Tumor necrosis factor alpha was identified as the main inducer of OSCAR expression in monocytes. CONCLUSION: These data suggest that the osteoclast costimulation pathway is activated in RA. OSCAR is induced in monocytes of RA patients, facilitating their differentiation into osteoclasts and bone resorption.