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Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
15843449 Changes of cartilage and bone markers after intra-articular glucocorticoid treatment with 2005 Dec BACKGROUND: Joint immobilisation improves the therapeutic effect of intra-articular glucocorticoid injection for knee synovitis. This may be due to retarded steroid resorption by immobilisation, a procedure that also could influence cartilage and bone metabolism. OBJECTIVE: To evaluate changes in cartilage and bone turnover after intra-articular glucocorticoid treatment for knee synovitis with and without postinjection rest. METHODS: 20 patients with rheumatoid arthritis and knee synovitis were randomised to 24 hour bed rest or to normal activity after intra-articular glucocorticoid treatment. Serum and urine markers of cartilage and bone turnover were studied for two weeks. Cartilage oligomeric matrix protein (COMP) was used as a marker of cartilage turnover, osteocalcin as marker of bone formation, and deoxipyridinoline (DPD) as marker of bone resorption. RESULTS: After the glucocorticoid injection COMP levels decreased in both groups (p<0.001), but significantly more in resting patients. Serum osteocalcin levels decreased significantly (p<0.001) without any difference between the groups. DPD was unchanged in both groups. CONCLUSIONS: Intra-articular glucocorticoid treatment for knee synovitis reduced serum COMP, which suggests that such treatment may have a cartilage protective effect. The slightly larger decrease of serum COMP in the resting group may reflect a lower clearance of COMP from the joint cavity. Serum osteocalcin was temporarily reduced, indicating a reversible suppression of bone formation.
15358625 Proinflammatory mediators elicit secretion of the intracellular B-lymphocyte stimulator po 2005 Jan 15 We have recently shown that granulocyte-colony-stimulating factor (G-CSF)- and interferon-gamma (IFN-gamma)-activated human neutrophils accumulate and release remarkable amounts of soluble B-lymphocyte stimulator (BLyS) in vitro. In this study, we provide evidence that neutrophils migrating into skin window exudates (SWEs) developed in healthy volunteers and in patients with rheumatoid arthritis (RA), synthesized, and released BLyS in response to locally produced G-CSF. Accordingly, the concentrations of soluble BLyS in SWEs were significantly more elevated than in serum. Because the levels of SWE BLyS, but not SWE G-CSF, were higher in patients with RA than in healthy subjects, we examined the effect of CXCL8/IL-8, C5a, and other proinflammatory mediators that dramatically accumulate in RA SWEs and in inflamed synovial fluids. We show that CXCL1/GROalpha, CXCL8/IL-8, C5a, immune complexes, tumor necrosis factor-alpha (TNF-alpha), leukotriene B4, N-formyl-methionyl-leucyl-phenylalanine (fMLP), and lipopolysaccharide (LPS), which by themselves do not induce BLyS de novo synthesis, act as potent secretagogues for BLyS, which is mainly stored in Golgi-related compartments within G-CSF-treated neutrophils, as determined by immunogold electron microscopy. This action is pivotal in greatly amplifying neutrophil-dependent BLyS release in SWEs of patients with RA compared with healthy subjects. Collectively, our data uncover a novel mechanism that might dramatically exacerbate the release of BLyS by neutrophils during pathologic inflammatory responses.
16325657 Rheumatic complications of human immunodeficiency virus infection in the era of highly act 2005 Dec OBJECTIVE: To describe the impact of the introduction of highly active antiretroviral therapy (HAART) on the nature and frequency of rheumatic complications in human immunodeficiency virus (HIV)-infected patients. METHODS: Case report and systematic review of a newly described syndrome of rheumatic immune reconstitution syndrome and prospective longitudinal cohort study analyzing the frequency and nature of rheumatic complications in the setting of HIV infection from 1989 through 2000. RESULTS: A newly described syndrome of either the de novo appearance or the exacerbation of clinically occult autoimmunity following immune reconstitution from HAART is described. Including the present case report, 32 cases have been individually described with sarcoidosis and autoimmune thyroid disease being most common with arthritis and various forms of connective tissue disease making up the rest. The mean onset to their appearance following HAART was nearly 9 months and most resolved with little or no therapy. In addition, a longitudinal analysis of 395 HIV-infected patients from 1989 to 2000 designed to detect the appearance of rheumatic complications has revealed a dramatic decline in certain problems such as reactive arthritis, psoriatic arthritis, and various forms of connective tissue disease. New rheumatic complications possibly due to the effects of longer survival and metabolic derangements associated with this form of therapy are now being described and may become more formidable problems in this population in the future. CONCLUSIONS: HAART has had a profound beneficial effect on survival in HIV-infected patients but has also contributed to both an altered frequency and a different nature of rheumatic complications now being observed in this population. Rheumatologists need to be aware of these changes to provide optimal diagnosis and treatment for this group.
16710710 Sick leave as a predictor of job loss in patients with chronic arthritis. 2006 Nov OBJECTIVES: To study the occurrence and duration of sick leave as potential risk factors for permanent job loss after 24 months among 112 individuals with chronic arthritis and a disease related problem at work. METHODS: Data collection was embedded in a multicentre randomised controlled trial in which the cost-effectiveness of a multidisciplinary job retention vocational rehabilitation programme for employees with chronic arthritis and a disease related problem at work was compared to usual outpatient care. Sick leave (complete or partial) was defined as absenteeism reported to the employer and permanent job loss as receiving a full work disability pension or unemployment. The association between sick leave at baseline and job loss after 24 months was investigated by multivariate logistic regression analysis, including those variables that were univariately significantly associated with job loss after 24 months. RESULTS: At baseline, 60 of the 112 subjects (54%) were on sick leave, with a mean duration of 18.7 weeks, in half of these patients the sick leave was complete. After 24 months, 26 of the 112 patients (23%) had lost their job. The presence of complete sick leave (OR 4.74, 95% CI 1.86-12.07) and the depression score of the hospital anxiety and depression scale (OR 1.18, 95% CI 1.02-1.36) were significantly and independently associated with job loss after 2 years follow-up. CONCLUSION: The occurrence of complete sick leave was found to be an independent risk factor for job loss in patients with chronic arthritis who have a disease related problem at work.
16723203 The NF-kappaB inhibitor pyrrolidine dithiocarbamate blocks IL-1beta induced hyaluronan syn 2006 Jun The glycosaminoglycan hyaluronan is not merely the simple space filling substance it was long thought to be but is instead being increasingly recognized as a key player in numerous biological processes ranging from embryogenesis to the process of aging. Alterations in hyaluronan syntheses play an important role in ailments associated with aging such as rheumatoid arthritis, atherosclerosis and many forms of cancers, e.g. prostate cancers that mostly affect the elderly. Despite the increasing recognition of hyaluronan as a critical player in many disorders, little is known about the intracellular mechanisms involved in the regulation of the genes encoding hyaluronan synthases (HAS). Herein, evidence is provided that in type-B synoviocytes (TBS) HAS1 is a gene that depends on the transcription factor nuclear factor kappa B (NF-kappaB) for its activation. Stimulating such cells with IL-1beta results in a dose and time dependent activation of HAS1. Pyrrolidine dithiocarbamate (PDTC) blocks IL-1beta induced HAS1 activation entirely. Furthermore, PDTC treatment also prevents the degradation of the IkappaBalpha in TBS as shown by Western blot experiments. EMSA data confirm that PDCT, at concentrations sufficient to completely block IL-1beta induced HAS1 transcription, also entirely blocks IL-1beta induced NF-kappaB translocation. The reported findings stress important differences among the genes encoding hyaluronan and point at a role of HAS1 in inflammatory processes.
16527311 Adalimumab-associated optic neuritis. 2006 May 15 We present, to our knowledge, the first published cases of optic neuritis associated with adalimumab, a medication in the class of anti-tumor necrosis factor-alpha (TNF-alpha) antagonists. Approved in recent years by the FDA, adalimumab (Humira, Abbott Laboratories; Abbott Park, IL) is a recombinant monoclonal antibody that targets and blocks the physiologic effects of TNF. Other TNF antagonists have had associations with optic neuritis and demyelinating events.
15494359 A linguistic framework for assessing the quality of written patient information: its use i 2005 Jun Patient information leaflets are an important adjunct to verbal exchange between doctor and patient. Their value is dependent upon whether they contain useful information from the viewpoint of the patient and are easily understood. We developed a framework based upon linguistic theory for assessing the quality of written patient information and applied it to a set of leaflets about methotrexate treatment. Items included the overall structure of the text, the technicality of the vocabulary used, the number of content words per clause ('lexical density'), and the clarity of the role relationship between author and reader. The leaflets consisted of up to nine identifiable sections (range 3-8): background information about the drug, summary of its use, dosage instructions, outline of benefits and side-effects, monitoring information, constraints on patient behavior, storage instructions, and clinical contact availability. Most leaflets contained a high number of content words per clause and the identity of the author was clear in only three (17%). Linguistic analysis provides highly relevant information about written patient information. Together with critical assessment of factual and visual aspects, consideration of key linguistic features should improve the quality of informational texts for our patients.
16100340 Further evidence that a cartilage-pannus junction synovitis predilection is not a specific 2005 Sep BACKGROUND: Qualitative differences in synovitis between the cartilage-pannus junction (CPJ) region and the adjoining suprapatellar pouch (SPP) have been reported in rheumatoid arthritis and the spondyloarthropathies. OBJECTIVE: To determine if the distribution of synovitis is the same in osteoarthritis (OA) using sensitive measures of inflammation derived from dynamic, contrast enhanced magnetic resonance imaging (DEMRI). METHODS: 20 subjects with established OA of the knee were recruited. Conventional MR images together with the DEMRI measurements were obtained. Areas of synovitis at the CPJ region and at a distant site in the SPP were calculated; differences in CPJ and SPP synovitis were determined using DEMRI parameters: the initial rate of contrast enhancement (IRE) and maximal enhancement (ME). RESULTS: The area of synovitis was significantly greater adjacent to the CPJ than in the SPP. IRE and ME measures were greater at the CPJ than the SPP. CONCLUSIONS: The magnitude of synovitis at the CPJ is not disease-specific and applies across the spectrum of degenerative disease as well as inflammatory diseases.
16207316 Differential expression of chemokine receptors on peripheral blood B cells from patients w 2005 Chemokines and their receptors are essential in the recruitment and positioning of lymphocytes. To address the question of B cell migration into the inflamed synovial tissue of patients with rheumatoid arthritis (RA), peripheral blood naive B cells, memory B cells and plasma cells were analyzed for cell surface expression of the chemokine receptors CXCR3, CXCR4, CXCR5, CCR5, CCR6, CCR7 and CCR9. For comparison, B cells in the peripheral blood of patients with the autoimmune disease systemic lupus erythematosus (SLE) or with the degenerative disease osteoarthritis (OA) were analyzed. Expression levels of chemokine receptors were measured by flow cytometry and were compared between the different patient groups and healthy individuals. The analysis of chemokine receptor expression showed that the majority of peripheral blood B cells is positive for CXCR3, CXCR4, CXCR5, CCR6 and CCR7. Whereas a small fraction of B cells were positive for CCR5, practically no expression of CCR9 was found. In comparison with healthy individuals, in patients with RA a significant fraction of B cells showed a decreased expression of CXCR5 and CCR6 and increased levels of CXCR3. The downregulation of CXCR5 correlated with an upregulation of CXCR3. In patients with SLE, significant changes in CXCR5 expression were seen. The functionality of the chemokine receptors CXCR3 and CXCR4 was demonstrated by transmigration assays with the chemokines CXCL10 and CXCL12, respectively. Our results suggest that chronic inflammation leads to modulation of chemokine receptor expression on peripheral blood B cells. However, differences between patients with RA and patients with SLE point toward a disease-specific regulation of receptor expression. These differences may influence the migrational behavior of B cells.
16357749 Immunologic mechanisms in the pathogenesis of rheumatoid arthritis. 2005 Jun Although much is known about the etiology and pathogenesis of rheumatoid arthritis (RA), our understanding of the immune pathways remains incomplete. The observed clinical and pathologic manifestations result from activation of several interrelated immune pathways. Current concepts of RA pathogenesis, supported by animal models, laboratory studies, and clinical observation, have reestablished and revised some of the original views. Early proposals emphasized the importance of autoantibodies and immune complexes in the initiation of RA, suggested a role for T cells in the inflammatory response characteristic of RA, and based disease perpetuation on an imbalance in the cytokine networks. We now recognize that each of these interrelated mechanisms significantly contributes to RA pathogenesis, including T cells that can help initiate and perpetuate the disease. This article reviews the major components and immune pathways involved in RA and briefly discusses the animal models that contribute to our understanding. Although a unified theory of RA pathogenesis may not be possible at this time, a paradigm is presented that considers the immune pathways that contribute to disease progression and joint destruction. These pathways may have important implications for treatment, because their modulation by biologic response modifiers (BRMs) directed toward specific targets provides benefits to patients with RA. BRMs are a new class of therapeutic agents derived from biologically active molecules and designed to modulate specific immune or inflammatory pathways. Although currently approved BRMs still have limitations, choosing an appropriate target, possibly early rather than late in the immune response, might result in new and improved therapies for RA.
16417052 Intra-articular steroid hip injection for osteoarthritis: a survey of orthopedic surgeons 2005 Dec BACKGROUND: Intra-articular steroid hip injection (IASHI) has been prescribed for painful hip arthritis since the 1950s, but with advances in medical and surgical management its role is less certain today. There are very few published data on the utility or prescribing patterns of IASHI. METHODS: We developed a questionnaire to seek expert opinion on IASHI that we distributed to practising Ontario-based members of the Canadian Orthopaedic Association. We systematically describe the current practices and expert opinion of 99 hip surgeons (73% response rate), focusing on indications, current use and complications experienced with IASHI. RESULTS: Only 56% of surgeons felt that IASHI was therapeutically useful, with 72% of surgeons estimating that 60% or less of their patients achieved even transient benefit from IASHI. One-quarter of the surgeons believe that IASHI accelerates arthritis progression, most of whom had stated that it would be no great loss if IASHI was no longer available. Nineteen percent of the surgeons believed that the infection rate related to total hip arthroplasty (THA) may be increased after IASHI, and this was associated with fewer IASHIs ordered per year, compared with the number prescribed by those who did not feel that infection rates would increase. CONCLUSIONS: This systematic collection of expert opinions demonstrates that substantial numbers of surgeons felt that, in their patients, IASHI was not therapeutically helpful, may accelerate arthritis progression or may cause increased infectious complications after subsequent THA.
16365688 Human foamy virus bel1 sequence in patients with autoimmune rheumatic diseases. 2006 Sep Since the association between human foamy virus (HFV) with rheumatic autoimmune diseases remains controversial, this study was designed to determine the relationship between HFV and systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), or progressive systemic sclerosis (PSS). The bel1 and Pol sequences of HFV were measured by reverse transcriptase-polymerase chain reaction (RT-PCR) in plasma and by PCR in peripheral blood mononuclear cells (PBMC) from patients with SLE, RA, and PSS. Antibodies against Bel1 and Pol were assessed by enzyme-linked immunosorbent assay. Active HFV infections were detected by a Bel1-responsive indicator cell line. The bel1 sequence was detected in the plasma (SLE 59, RA 32, and PSS 63%) and PBMC (SLE 54, RA 71, and PSS 57%). However, active HFV infection existed only in patients with the bel1 sequence in both plasma and PBMC. In SLE patients, antibodies against Bel1 (7.1%) and Pol (4.5%) were also detected. The results suggest a possible association between HFV infection and these autoimmune rheumatic diseases.
16356193 B lymphocyte stimulator (BLyS) isoforms in systemic lupus erythematosus: disease activity 2006 Considerable evidence points to a role for B lymphocyte stimulator (BLyS) overproduction in murine and human systemic lupus erythematosus (SLE). Nevertheless, the correlation between circulating levels of BLyS protein and disease activity in human SLE is modest at best. This may be due to an inadequacy of the former to reflect endogenous BLyS overproduction faithfully, in that steady-state protein levels are affected not just by production rates but also by rates of peripheral utilization and excretion. Increased levels of BLyS mRNA may better reflect increased in vivo BLyS production, and therefore they may correlate better with biologic and clinical sequelae of BLyS overexpression than do circulating levels of BLyS protein. Accordingly, we assessed peripheral blood leukocyte levels of BLyS mRNA isoforms (full-length BLyS and DeltaBLyS) and plasma BLyS protein levels in patients with SLE, and correlated these levels with laboratory and clinical features. BLyS protein, full-length BLyS mRNA, and DeltaBLyS mRNA levels were greater in SLE patients (n = 60) than in rheumatoid arthritis patients (n = 60) or normal control individuals (n = 30). Although full-length BLyS and DeltaBLyS mRNA levels correlated significantly with BLyS protein levels in the SLE cohort, BLyS mRNA levels were more closely associated with serum immunoglobulin levels and SLE Disease Activity Index scores than were BLyS protein levels. Moreover, changes in SLE Disease Activity Index scores were more closely associated with changes in BLyS mRNA levels than with changes in BLyS protein levels among the 37 SLE patients from whom repeat blood samples were obtained. Thus, full-length BLyS and DeltaBLyS mRNA levels are elevated in SLE and are more closely associated with disease activity than are BLyS protein levels. BLyS mRNA levels may be a helpful biomarker in the clinical monitoring of SLE patients.
17165005 Carpal tunnel syndrome caused by volar dislocation of the lunate in a patient with rheumat 2006 We report a case of carpal tunnel syndrome caused by volar dislocation of the lunate in a patient with rheumatoid arthritis. A 74-year-old woman complained of numbness in her fingers. Carpal tunnel syndrome was diagnosed, and carpal tunnel release was performed. However, the symptoms recurred. Three-dimensional computed tomography and magnetic resonance imaging revealed volar dislocation of the lunate and synovitis around the distal radioulnar joint, respectively. Resection of the lunate and the Sauvé-Kapandji procedure were effective.
16881100 Reduction of cardiovascular risk factors with longterm fish oil treatment in early rheumat 2006 Oct OBJECTIVE: Rheumatoid arthritis (RA) is associated with increased risk for cardiovascular (CV) events through multiple factors. Fish oil has been shown to reduce symptoms in RA and to reduce CV risk. We assessed the effect of an antiinflammatory dose of fish oil on CV risk factors within a program of combination chemotherapy for patients with early RA. METHODS: Patients who chose not to take fish oil (n = 13) were compared with patients who achieved a sustained elevation of eicosapentaenoic acid (EPA) in plasma phospholipid fatty acids (> 5% total fatty acids) while taking fish oil over a 3-year period (n = 18). We examined cellular content of arachidonic acid (AA), synthesis of thromboxane A2 and prostaglandin E2, use of nonsteroidal antiinflammatory drugs (NSAID), traditional CV lipid risk factors, and disease activity at 3 years. RESULTS: At 3 years, AA (as a proportion of AA plus long-chain n-3 fatty acids that can compete with AA for cyclooxygenase metabolism) was 30% lower in platelets and 40% lower in peripheral blood mononuclear cells in subjects taking fish oil. Serum thromboxane B2 was 35% lower and lipopolysaccharide-stimulated whole-blood prostaglandin E2 was 41% lower with fish oil ingestion compared to no fish oil. NSAID use was reduced by 75% from baseline with fish oil (p < 0.05) and by 37% without fish oil (NS). Favorable changes in fasting blood lipids were seen with, but not without fish oil. Remission at 3 years was more frequent with fish oil use (72%) compared to no fish oil (31%). CONCLUSION: Fish oil reduces cardiovascular risk in patients with RA through multiple mechanisms.
16751383 A membrane form of TNF-alpha presented by exosomes delays T cell activation-induced cell d 2006 Jun 15 In common with many other cell types, synovial fibroblasts produce exosomes. In this study, we show that the exosomes produced by synovial fibroblasts obtained from individuals with rheumatoid arthritis (RASF), but not exosomes produced by synovial fibroblasts obtained from individuals with osteoarthritis, contain a membrane bound form of TNF-alpha as demonstrated by colloidal gold immunostaining of TNF-alpha and confirmed by both Western blot and mass spectrometry. The RASF-derived exosomes, but not exosomes derived from fibroblasts obtained from individuals with osteoarthritis, are cytotoxic for the L929 cell, a TNF-alpha-sensitive cell line, and stimulate activation of NF-kappaB and induction of collagenase-1 in RASF. These effects are blocked by addition of soluble TNFR1 (sTNFbp), suggesting that a TNF-alpha-signaling pathway mediates these biological activities. sTNFbp also reduced the production of exosomes by RASF, suggesting the interruption of a positive amplification loop. Exosomes can transmit signals between cells, and RASF exosomes, effectively taken up by anti-CD3-activated T cells, activated AKT and NF-kappaB and rendered these activated T cells resistant to apoptosis. Neutralization of exosomal membrane TNF-alpha by sTNFbp partially reversed this resistance, suggesting that not only TNF-alpha but also additional exosomal proteins may contribute to the development of apoptosis resistance.
16508968 Vasoactive intestinal peptide induces CD4+,CD25+ T regulatory cells with therapeutic effec 2006 Mar OBJECTIVE: CD4+,CD25+ T regulatory cells (Treg) control the immune response to a variety of antigens, including self antigens, and may offer opportunities to intervene in the course of autoimmune diseases. Several models support the idea of the peripheral generation of CD4+,CD25+ Treg from CD4+,CD25- T cells, but little is known about the endogenous factors and mechanisms controlling the peripheral expansion of CD4+,CD25+ Treg. We undertook this study to investigate the capacity of the vasoactive intestinal peptide (VIP), an immunosuppressive antiarthritic neuropeptide, to induce functional Treg in vivo during the development of collagen-induced arthritis (CIA). METHODS: We measured the number of CD4+,CD25+ Treg following VIP administration to CIA mice, and we characterized their phenotype and their ability to suppress activation of autoreactive T cells. We determined the capacity of VIP to induce Treg in vitro as well as the use of Treg in the treatment of CIA, measuring the clinical evolution and the inflammatory and autoimmune components of the disease. RESULTS: The administration of VIP to arthritic mice resulted in the expansion of CD4+,CD25+,Foxp3+ Treg in the periphery and joints, which inhibited autoreactive T cell activation/expansion. VIP induced more efficient suppressors on a per-cell basis. The VIP-generated CD4+,CD25+ Treg transfer suppressed and significantly ameliorated the progression of the disease. CONCLUSION: These results demonstrate the involvement of the generation of Treg in the therapeutic effect of VIP on CIA. The generation of highly efficient Treg by VIP ex vivo could be used as an attractive therapeutic tool in the future, avoiding the administration of the peptide to patients with rheumatoid arthritis.
16396706 Infliximab therapy does not modify MMP-2 and MMP-9 serum concentrations in chronic arthrit 2005 Nov OBJECTIVE: Matrix metalloprotease-2 (MMP-2) and matrix metalloprotease-9 (MMP-9) play a key role in tissue remodelling after processes such as joint destruction in rheumatoid arthritis. Their expression may reflect the disease activity and they could therefore represent a useful marker to assess the efficacy of therapy. In this study MMP-2 and MMP-9 serum were evaluated in patients with chronic arthritis during therapy with the anti-TNFalpha mAb, infliximab. METHODS: Fifty patients with chronic arthritis, 26 with rheumatoid arthritis and 24 with undifferentiated chronic arthritis, were recruited and treated with infliximab (3 mg/kg). Serum concentrations of MMP-2 and MMP-9 were serially measured by gelatine zymography at baseline and after two and fourteen weeks of infliximab therapy. DAS-28 and ACR response criteria were applied to assess disease activity and clinical improvement. Twenty-four healthy donors were included in the study as controls. RESULTS: Although therapy with infliximab induced a statistically significant reduction of the DAS-28 score and improvement of the ACR clinical response, MMP-2 and MMP-9 serum concentrations were not modulated during therapy with infliximab. CONCLUSIONS: Our study provides further evidence that blocking TNFalpha by infliximab is a powerful tool in the management of chronic arthritis. Nevertheless, infliximab does not seem to be able to modify the serum expression of MMP-2 and MMP-9, probably because modification of these enzymes is restricted to the site of joint inflammation and serum detection can not truly mirror the local situation. Additional soluble factors correlating with joint damage should be investigated as possible markers for monitoring anti-TNFalpha therapy.
15899028 Levels of gastrin-releasing peptide and substance P in synovial fluid and serum correlate 2005 It is well known that cytokines are highly involved in the disease process of rheumatoid arthritis (RA). Recently, targeting of neuropeptides has been suggested to have potential therapeutic effects in RA. The aim of this study was to investigate possible interrelations between five neuropeptides (bombesin/gastrin-releasing peptide (BN/GRP), substance P (SP), vasoactive intestinal peptide, calcitonin-gene-related peptide, and neuropeptide Y) and the three cytokines tumour necrosis factor (TNF)-alpha, IL-6, and monocyte chemoattractant protein-1 in synovial fluid of patients with RA. We also investigated possible interrelations between these neuropeptides and soluble TNF receptor 1 in serum from RA patients. Synovial fluid and sera were collected and assayed with ELISA or RIA. The most interesting findings were correlations between BN/GRP and SP and the cytokines. Thus, in synovial fluid, the concentrations of BN/GRP and SP grouped together with IL-6, and SP also grouped together with TNF-alpha and monocyte chemoattractant protein-1. BN/GRP and SP concentrations in synovial fluid also grouped together with the erythrocyte sedimentation rate. In the sera, BN/GRP concentrations and soluble TNF receptor 1 concentrations were correlated. These results are of interest because blocking of SP effects has long been discussed in relation to RA treatment and because BN/GRP is known to have trophic and growth-promoting effects and to play a role in inflammation and wound healing. Furthermore, the observations strengthen a suggestion that combination treatment with agents interfering with neuropeptides and cytokines would be efficacious in the treatment of RA. In conclusion, BN/GRP and SP are involved together with cytokines in the neuroimmunomodulation that occurs in the arthritic joint.
16901955 Rheumatoid factor and antibodies to cyclic citrullinated peptides are associated with seve 2007 Jan OBJECTIVE: To study antibodies to cyclic citrullinated peptides (anti-CCP) and rheumatoid factor in patients with active, severe extra-articular rheumatoid arthritis (ExRA) compared with controls without ExRA. METHODS: 35 consecutive patients with severe ExRA manifestations according to predefined criteria were studied. 70 patients with rheumatoid arthritis, but no ExRA manifestations, individually matched for age, sex and disease duration, served as controls. Patients were included when ExRA was diagnosed, before any new treatment was started. Anti-CCPs were detected with ELISA, rheumatoid factor was quantified using nephelometry and anti-nuclear antibodies (ANA) were investigated using indirect immune fluorescence. RESULTS: Anti-CCPs were detected in 77% of patients with ExRA versus 56% of controls without ExRA (p = 0.03). Anti-CCP levels also tended to be higher in patients with ExRA (p = 0.09). Rheumatoid factor was detected in 94% v 71% of patients and controls, respectively (p = 0.006), and rheumatoid factor levels were higher in patients with ExRA (median interquartile range (IQR) 245 IU/ml (94-604) v 73 IU/ml (not detected-165); p = 0.001). Levels and occurrence of ANA did not differ between patients with ExRA and controls. Patients with ExRA had higher swollen joint counts and C reactive protein levels, but no correlations were found between anti-CCP or rheumatoid factor levels and these measures within the ExRA group. CONCLUSION: Rheumatoid factor is strongly associated with severe ExRA manifestations in patients with rheumatoid arthritis, and a similar but weaker association exists for anti-CCPs. This suggests a role for rheumatoid factor and anti-CCP in the pathogenesis of ExRA.