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ID PMID Title PublicationDate abstract
12223282 Mannan-binding lectin: clinical significance and applications. 2002 Sep 19 Mannan-binding lectin (MBL) is a collectin (protein with both collagen-like and C-type lectin domains) synthesised in the liver and secreted into the bloodstream. Its plasma concentration is for the most part genetically determined by a series of allelic dimorphisms located both in the structural gene and in the promoter region. Genotypes made up of combinations of seven haplotypes are mainly responsible for a 1000-fold concentration variation found in human beings. MBL is a pattern recognition molecule able to bind repeating sugar arrays on many microbial surfaces, and can activate complement via associated serine proteases. A poorly defined proportion (roughly 10%) of the population with the lowest MBL concentrations is thought to be MBL insufficient and more vulnerable to a variety of infectious and noninfectious disorders. The evidence that MBL makes an important contribution to innate immunity, by increasing susceptibility to disease and/or affecting the course of disease, is discussed in detail. Preliminary results from MBL replacement therapy are encouraging, and extension of this approach to large-scale randomised clinical trials would provide solid evidence concerning the physiological significance of this protein.
12588667 The chemokines CCL5, CCL2 and CXCL12 play significant roles in the migration of Th1 cells 2003 Feb As the T-cell population in the synovial tissue (ST) in rheumatoid arthritis (RA) is dominated by T helper (Th) 1 cells, this study was designed to examine whether there is a preferential migration of polarized T cells to ST, and to identify the chemokines responsible for the migration. This was done by developing 10 T-cell clones specific for an arbitrary antigen (mouse immunoglobulin G (IgG)) from the peripheral blood (PB) of a healthy donor sensitized to mouse IgG. The Th polarizations of the clones were determined by measuring secreted interferon-gamma and interleukin-4, following anti-CD3 stimulation. Migration to pools of RA ST cell-derived supernatants was analysed. Expression of the chemokine receptors CCR1, CCR2, CCR3, CCR4, CCR5, CCR6, CCR7, CCR8, CXCR3 and CXCR4 were analysed by flow cytometry. Th1 clones showed significantly higher migration to RA ST cell-derived supernatant compared with Th2 clones. Blocking of either of the chemokines, CCL5 or CCL2, strongly inhibited migration of the Th1 cells between 56 and 77%, while blocking of CXCL12 inhibited migration between 44 and 61%. Blocking of CXCL10 had only a minor inhibitory effect. Our results demonstrate a selective migration of Th1 cells to RA ST supernatant and that blocking either CCL5, CCL2 or CXCL12 significantly inhibits T-cell migration. This indicates that CCL5, CCL2 and CXCL12 play significant roles in attracting Th1 cells towards the RA ST, and may prove potent targets for obstructing T-cell migration to the synovium.
12810427 Prevalence of self reported musculoskeletal diseases is high. 2003 Jul OBJECTIVES: To present the prevalence of self reported musculoskeletal diseases, the coexistence of these diseases, the test-retest reliability with six months in between, and the association with musculoskeletal pain symptoms. METHODS: Twelve layman descriptions of common musculoskeletal diseases were part of the questionnaires of a prospective cohort study of a random sample in the general Dutch population aged 25 years or more (baseline: n=3664, follow up after six months: n=2338). Data collection also included information about pain relating to five different anatomical areas. RESULTS: Osteoarthritis of the knee (men 10.1%, women 13.6%) was amongst the most reported musculoskeletal diseases, whereas the figures for self reported rheumatoid arthritis (RA) were 1.6% and 4.6% for men and women, respectively. The coexistence of these diseases is high: 47 of the 66 combinations were reported more often than would be expected if they were independent of each other (p<0.05). For most diseases the test-retest reliability was good (kappa between 0.6 and 0.8), but for repetitive strain injury (kappa=0.37) and chronic arthritis other than RA (kappa=0.44) the agreement was fair to moderate. All complaints of pain were more often reported by those with musculoskeletal diseases than those without those diseases, and the pain pattern was disease-specific. CONCLUSIONS: Self reported musculoskeletal diseases are highly prevalent, with a fair to good reliability and a disease-specific pain pattern. Health surveys are a limited but valuable source of information for this group of health problems, which is not available from most other sources of information.
14622362 Drug-induced bilateral transient myopia with the sulphonamide sulphasalazine. 2003 Nov Whereas there are numerous reported ocular side effects from systemic sulpha medication, most are rare and reversible, with myopia being the most common reaction observed. A case report is presented of sudden bilateral onset of -1.0 DS of myopia (from -3.0 to -4.0 DS) in a young adult female following the addition of a sulphonamide (sulphasalazine) to oral non-steroidal anti-inflammatory treatment (meloxicam) for rheumatoid arthritis. The myopia regressed to -3.50 DS after 2 weeks when all medication was withdrawn and stabilised at this level when subsequent treatment was resumed after 8 weeks with the non-steroidal anti-inflammatory drug celecoxib. The case indicates that account needs to be taken of the possibility that relatively modest myopic shifts encountered in young adult contact lens wearers may be associated with concomitant systemic medication.
12855687 Oligomerization of soluble Fas antigen induces its cytotoxicity. 2003 Sep 19 Soluble Fas antigen can protect cells against Fas-mediated apoptosis. High level soluble Fas antigen characteristic for blood of patients with autoimmune disease or cancer is believed to prevent the elimination of autoimmune lymphocytes or tumor cells. Here we first report that human recombinant FasDeltaTM, i.e. soluble Fas generated by alternative splicing of the intact exon 6, is capable of inducing death of transformed cells by "reverse" apoptotic signaling via transmembrane Fas ligand. FasDeltaTM, as well as transmembrane Fas antigen, can be either monomeric or oligomeric, and both its forms are efficient in blocking Fas-mediated apoptosis, although the cytotoxic activity is exhibited solely by the latter. An in vivo analysis of soluble Fas antigen showed that unlike in healthy controls, nearly the total FasDeltaTM present in sera of rheumatoid arthritis patients was oligomeric. This resulted in suppression of cell proliferation in the experimental sera and in its promotion in controls. Thus, oligomerization/depolymerization of soluble Fas antigen can regulate its activity and contribute to the pathogenesis of autoimmune diseases and cancer.
15515777 Serum soluble CD30 levels in Behçet's disease. 2004 Jul Behçet's disease is associated with the inflammatory response. Several reports indicate the presence of primarily CD4+ T cells of the Th1 subtype in the inflammation process of the disease. Serum soluble CD30 (sCD30) is reported to be released from CD4+ Th2 type cells and has been suggested to be a marker of Th2 activity. In this study, serum sCD30 levels were measured in active and inactive patients with Behçet's disease, healthy controls and a group of patients with rheumatoid arthritis, typical Th1 disorder using enzyme immunoassay kit. Mean sCD30 value of 54 active patients were found significantly higher than in those of 17 inactive patients (p = 0.027), 20 healthy controls (p = 0.040) and 25 patients with rheumatoid arthritis (p < 0.001). There was a significant correlation between increased sCD30 levels and clinical activity index in active patients with Behçet's disease. High serum levels of sCD30 may reflect the activation of CD4+ T cells or a subset of them in active BD patients. In addition to serum sCD30 levels, measurements of the Th2 cytokines may be a helpful tool for the evaluation of Th2 activity in Behçet's disease.
12729108 Total elbow replacement using the Kudo prosthesis. Clinical and radiological review with f 2003 Apr Between 1993 and 1996, we undertook 35 Kudo 5 total elbow replacements in a consecutive series of 31 rheumatoid patients. A total of 25 patients (29 procedures) was evaluated at a mean follow-up of six years (5 to 7.5) using the Mayo Clinic performance index. In addition, all patients were assessed for loosening using standard anteroposterior and lateral radiographs. At review, 19 elbows (65%) had either no pain or mild pain, ten (35%) had moderate pain and none had severe pain. The mean arc of flexion/extension was 94 degrees (35 to 130) and supination/pronation was 128 degrees (30 to 165). A fracture of the medial epicondyle occurred during surgery in one patient. This was successfully treated with a single AO screw and a standard Kudo 5 implant was inserted. Postoperatively, there were no infections. One patient had a dislocation which was treated by closed reduction and five had neurapraxia of the ulnar nerve. Radiologically, there was no evidence of loosening of the humeral component, but two ulnar components had progressive radiolucent lines suggestive of loosening. Two other ulnar components had incomplete and non-progressive radiolucent lines. With definite radiological loosening as the endpoint, the probability of survival of the Kudo 5 prosthesis at five years using the Kaplan-Meier method was 89%.
12759455 Localization of MHC class II/human cartilage glycoprotein-39 complexes in synovia of rheum 2003 Jun 1 Recently human cartilage gp-39 (HC gp-39) was identified as a candidate autoantigen in rheumatoid arthritis (RA). To further investigate the relevance of this Ag in RA, we have generated a set of five mAbs to a combination epitope of complexes of HC gp-39(263-275) and the RA-associated DR alpha beta 1*0401 HLA class II molecules. FACS studies revealed that these mAb recognize specific complexes on homozygous DR alpha beta 1*0401-positive B lymphoblastoid cells pulsed with HC gp-39(263-275). The best mAb, 12A, was further characterized using a set of irrelevant DR alpha beta 1*0401-binding peptides and truncated/elongated versions of HC gp-39(263-275) itself. The minimal epitope recognized in combination with DR alpha beta 1*0401 was HC gp-39(263-273). Peptides not encompassing HC gp-39(263-273) were not recognized. Three of five mAb were able to inhibit (up to 90%) the response of HC gp-39(263-275)-specific DR alpha beta 1*0401-restricted T cell hybridomas to peptide-pulsed APC or purified complexes. Using mAb 12A, we have been able to identify and localize dendritic cells that present DR alpha beta 1*0401/HC gp-39(263-275) complexes in synovial tissue of DR alpha beta 1*0401-positive RA patients, indicating local presentation of the HC gp-39(263-275) epitope in the inflamed target tissue by professional APC. These data support a role of HC gp-39 in the local autoimmune response that leads to chronic inflammation and joint destruction.
15246025 Sarcoidosis succumbs to antibiotics--implications for autoimmune disease. 2004 Jun From time to time there have been reports of autoimmune disease succumbing to tetracycline antibiotics, but many have assumed this was due to coincidence, or to some ill-defined 'anti-inflammatory property' of the tetracyclines. But now the inflammation of sarcoidosis has succumbed to antibiotics in two independent studies. This review examines the cell wall deficient (antibiotic resistant) bacteria which have been found in tissue from patients with sarcoidosis. It examines how such bacteria can infect the phagocytes of the immune system, and how they may therefore be responsible for not only sarcoid inflammation, but also for other autoimmune disease. Proof positive of a bacterial pathogenesis for Sarcoidosis includes not only the demonstrated ability of these studies to put the disease into remission, but also the severity of Jarisch-Herxheimer shock resulting from endotoxin release as the microbes are killed. Studies delineating the hormone responsible for phagocyte differentiation in the Th1 immune response, 1,25-dihydroxyvitamin D, are discussed, and its utility as a marker of Th1 immune inflammation is reviewed. Finally, data showing that the behavior of this hormone is also aberrant in rheumatoid arthritis, systemic lupus erythematosus, and Parkinson's, raise the possibility that these diseases may also have a CWD bacterial pathogenesis.
15140781 Health related quality of life in multiple musculoskeletal diseases: SF-36 and EQ-5D in th 2004 Jun OBJECTIVE: To examine the health related quality of life of persons with one or more self reported musculoskeletal diseases, as measured by the short form 36 item health status survey (SF-36) and the Euroqol questionnaire (EQ-5D). METHODS: A sample of Dutch inhabitants aged 25 years or more (n = 3664) participated in a questionnaire survey. Twelve lay descriptions of common musculoskeletal diseases were presented and the subjects were asked whether they had ever been told by a physician that they had any of these. Their responses were used to assess the prevalence of these conditions. Commonly used scores of SF-36 and descriptive scores from EQ-5D are presented, along with standardised differences between disease groups and the general population. SUBJECTS: with musculoskeletal diseases had significantly lower scores on all SF-36 dimensions than those without musculoskeletal disease, especially for physical functioning (SF-36 score (SE), 75.2 (0.5) v 87.8 (0.5)); role limitations caused by physical problems (67.1 (0.9) v 85.8 (0.8)); and bodily pain (68.5 (0.5) v 84.1 (0.5)). The worst health related quality of life patterns were found for osteoarthritis of the hip, osteoporosis, rheumatoid arthritis, and fibromyalgia. Those with multiple musculoskeletal diseases had the poorest health related quality of life. Similar results were found for EQ-5D. CONCLUSIONS: All musculoskeletal diseases involve pain and reduced physical function. The coexistence of musculoskeletal diseases should be taken into account in research and clinical practice because of its high prevalence and its substantial impact on health related quality of life.
15154113 Whole-genome scan, in a complex disease, using 11,245 single-nucleotide polymorphisms: com 2004 Jul Despite the theoretical evidence of the utility of single-nucleotide polymorphisms (SNPs) for linkage analysis, no whole-genome scans of a complex disease have yet been published to directly compare SNPs with microsatellites. Here, we describe a whole-genome screen of 157 families with multiple cases of rheumatoid arthritis (RA), performed using 11,245 genomewide SNPs. The results were compared with those from a 10-cM microsatellite scan in the same cohort. The SNP analysis detected HLA*DRB1, the major RA susceptibility locus (P=.00004), with a linkage interval of 31 cM, compared with a 50-cM linkage interval detected by the microsatellite scan. In addition, four loci were detected at a nominal significance level (P<.05) in the SNP linkage analysis; these were not observed in the microsatellite scan. We demonstrate that variation in information content was the main factor contributing to observed differences in the two scans, with the SNPs providing significantly higher information content than the microsatellites. Reducing the number of SNPs in the marker set to 3,300 (1-cM spacing) caused several loci to drop below nominal significance levels, suggesting that decreases in information content can have significant effects on linkage results. In contrast, differences in maps employed in the analysis, the low detectable rate of genotyping error, and the presence of moderate linkage disequilibrium between markers did not significantly affect the results. We have demonstrated the utility of a dense SNP map for performing linkage analysis in a late-age-at-onset disease, where DNA from parents is not always available. The high SNP density allows loci to be defined more precisely and provides a partial scaffold for association studies, substantially reducing the resource requirement for gene-mapping studies.
15213334 Welfare rights services for people disabled with arthritis integrated in primary care and 2004 Sep OBJECTIVE: To quantify the set-up costs and monetary benefits of a welfare rights service integrated within an NHS service provider, that selects eligible patients using the Health Assessment Questionnaire (HAQ) and offers welfare rights advice to assist in application for Disability Living Allowance and Attendance Allowance. METHOD: (1) DESIGN: a cost evaluation of a social intervention, screening with the HAQ and welfare rights advice in primary care and hospital settings. (2) SETTING: Eight general practices and four hospital rheumatology out-patient departments were selected from four localities in the southwest of England. (3) PARTICIPANTS: Two hundred and sixty-eight eligible patients with arthritis accepted an interview with a welfare rights officer (WRO) from a sample of 1989 service users identified from GPs' records and hospital out-patient lists. Two hundred and forty two service users expressed an interest in take up of the social intervention. (4) Service users with a HAQ score >/=1.5 were contacted by telephone and offered an appointment with an experienced WRO to help them complete a welfare benefit application form. A 'micro-costing' study was undertaken with assessment of monetary benefits received. RESULTS: The indicative set-up costs of similar welfare rights services are pound 8125 in a GP setting and pound 9307 per annum in a hospital setting at 2002 prices. Total annual unclaimed Disability Living Allowance/Attendance Allowance granted to successful claimants was pound 184,382 in the GP setting (n = 84 from 137) and pound 169,309 in the hospital setting (n = 79 from 131). CONCLUSIONS: Welfare rights advice received during a visit to a GP practice or a hospital out-patient department can substantially reduce the level of unclaimed benefit in arthritic populations including the elderly; with mobility and care difficulties. A welfare rights service integrated within a GP practice or hospital that screens people with arthritis using HAQ scores and encourages those with scores >/=1.5 to see a WRO for help with welfare benefit confers monetary benefits for service users that substantially outweigh set-up costs.
12927859 Role of the galactosyl moiety of collagen glycopeptides for T-cell stimulation in a model 2003 Sep 1 Two protected derivatives of beta-D-galactopyranosyl-5-hydroxy-L-lysine, in which HO-4 of galactose has been O-methylated or replaced by fluorine, have been prepared. The building blocks were incorporated at position 264 of the peptide fragment CII259-273 from type II collagen by solid-phase synthesis. The ability of these two glycopeptides, and two CII259-273 glycopeptides in which HO-4 of galactose was either unmodified or deoxygenated, to elicit responses from T-cell hybridomas obtained in a mouse model for rheumatoid arthritis was then determined. The hybridomas were all highly sensitive towards modifications at C-4 of the beta-D-galactosyl residue of CII259-273, highlighting the role of HO-4 as an important contact point for the T-cell receptor. Most likely, this glycopeptide hydroxyl group is involved in hydrogen bonding with the T-cell receptor.
12510364 [Recent development of selective cyclooxygenase-2 inhibitors]. 2002 Dec Nonsteroidal anti-inflammatory drugs(NSAIDs) are clinically effective against the inflammatory symptoms of rheumatoid arthritis. Recent attention has been focused on selective cyclooxygenase(COX)-2 inhibitors, a type of NSAID that inhibits a subtype of COX. Because of the different actions of COX-1 and COX-2, selective COX-2 inhibitors were expected to reduce adverse reactions such as gastrointestinal disorders. Various clinical studies have confirmed that the efficacy of COX-2 inhibitors for RA is similar to that of conventional NSAIDs, but they cause fewer severe gastrointestinal disorders. The incidence of complications related to renal dysfunction, such as edema and hypertension, is not different. Patients using selective COX-2 inhibitors have recently been reported to show an increase in thrombotic complications such as myocardial infarction. Therefore, more data on adverse events should be collected in the future from large-scale clinical studies to further clarify the actual value of selective COX-2 inhibitors.
11824958 Rheumatic manifestations of Bartonella infection in 2 children. 2002 Jan We describe 2 patients with very unusual rheumatological presentations presumably caused by Bartonella infection: one had myositis of proximal thigh muscles bilaterally, and the other had arthritis and skin nodules. Both patients had very high levels of antibody to Bartonella that decreased in association with clinical improvement. Bartonella infection should be considered in the differential diagnosis of unusual myositis or arthritis in children.
12687536 Low prevalence of antibodies to glucose-6-phosphate isomerase in patients with rheumatoid 2003 Apr OBJECTIVE: Arthritis in the K/BxN mouse model results from pathogenic immunoglobulins that recognize glucose-6-phosphate isomerase (GPI), a glycolytic enzyme residing in the cytoplasm of all cells. Antibodies directed against GPI can, alone, transfer arthritis to healthy recipients. Previous experiments have revealed significant titers of anti-GPI antibodies in the serum of many patients with rheumatoid arthritis (RA). We evaluated the generality of these observations in cohorts of patients with 12 different arthritic and chronic autoimmune diseases and in population-matched healthy control subjects. METHODS: Anti-GPI antibodies were assayed in 811 individual serum samples by enzyme-linked immunosorbent assay with 2 forms of GPI, recombinant and native. Results were confirmed by immunoblotting. RESULTS: Several patients had significantly elevated anti-GPI antibody titers, but without the prevalence or the specificity reported previously. Only 15% of RA patients had anti-GPI antibodies (range 12-29% in different cohorts), with a higher prevalence in patients with active disease. Psoriatic arthritis, undifferentiated arthritis, and spondylarthropathy patients also displayed anti-GPI antibodies at similar frequencies (12-25%). Similar titers were detected in a proportion (5-10%) of control subjects or patients with Crohn's disease or sarcoidosis. Very high titers were found in rare cases of RA and systemic lupus erythematosus. CONCLUSION: No disease-specific pattern of antibody positivity to GPI was apparent. While the antibody-mediated mechanism at play in the mouse model may exemplify a generic mechanism for some forms of arthritis in humans, GPI itself does not appear to be a target common to the majority of RA patients.
12421997 Synovial fluid from patients with rheumatoid arthritis inhibits neutrophil apoptosis: role 2002 Nov OBJECTIVE: In synovial fluid (SF) from patients with rheumatoid arthritis (RA), neutrophils are exposed to proinflammatory mediators endowed with either anti-apoptotic or pro-apoptotic properties. We investigated neutrophil apoptosis in the presence of SF from 11 RA patients. METHODS: SF was obtained from affected knees of 11 patients with RA. Human neutrophil apoptosis was evaluated by light microscopic examination and flow-cytometric analysis of annexin V binding. Immune complex-induced neutrophil activation was evaluated as superoxide anion production. Adenosine levels in SF were detected by chromatographic analysis and cytokine levels were studied by enzyme-linked immunosorbent assay. RESULTS: Spontaneous and immune complex-triggered neutrophil apoptosis was reduced by SF from eight out of 11 patients. Immune complex-induced neutrophil activation was unaffected by SF. The cytokines tested had no role in promoting the anti-apoptotic activity of SF. On the contrary, the anti-apoptotic activity of SF was found to depend on the presence of adenosine. Adenosine levels detected in the various samples of SF correlated significantly with the anti-apoptotic activity of the fluids and with the number of apoptotic neutrophils detected in the articular exudate. CONCLUSION: The microenvironment of rheumatoid SF is a proinflammatory milieu responsible for the in loco persistence of activated and long-surviving neutrophils. Adenosine plays a crucial role in this phenomenon, which is related to anti-apoptotic activity.
12062421 cDNA macroarray analysis of gene expression in synoviocytes stimulated with TNFalpha. 2002 Apr 24 Gene expression of synoviocytes stimulated with tumor necrosis factor-alpha (TNFalpha) was studied by macroarray analysis to elucidate the cellular response and identify new biological functions of known and unknown genes. 10035 cDNA clones were used to make cDNA macroarrays of representative genes. Synoviocytes expressed large amounts of fibronectin and collagen mRNA. Statistical analysis of the macroarray data revealed 26 genes, including six new genes, which underwent significant alteration of gene expression in response to TNFalpha stimulation. These findings suggest that the synoviocyte response to TNFalpha stimulation forms the basis of development of various aspects of the pathophysiology of rheumatoid arthritis.
15470475 Interleukin-1beta polymorphisms in Colombian patients with autoimmune rheumatic diseases. 2004 Dec Interleukin-1 beta (IL-1beta) exerts a range of inflammatory and immunomodulatory activities that are important in host defense and autoimmune response. The IL-1beta gene, located on chromosome 2 (2q13), is polymorphic. The influence of its polymorphism on 355 patients with autoimmune rheumatic diseases was examined. To this effect, 172 patients with rheumatoid arthritis (RA), 114 with systemic lupus erythematosus (SLE), and 69 with primary Sjogren's syndrome (pSS) were studied. The control group consisted of 392 matched healthy individuals. Genotyping of IL-1beta single-nucleotide polymorphisms (SNPs) at positions -511 (C/T) and + 3953 (C/T) was performed by the polymerase chain reaction-restriction fragment length polymorphism technique. In addition, levels of IL-1beta were measured by immunoassay in supernatants of lipopolysaccharide (LPS)-stimulated and nonstimulated peripheral blood monocytes (PBM) obtained from 19 homozygous individuals for the three most common IL-1beta likely haplotypes, all belonging to the control group. Allele + 3953T was protective for SLE (odds ratio (OR) = 0.57, 95% confidence intervals (CI) = 0.34-0.88, P = 0.01) as was the haplotype -511C + 3953T (OR = 0.43, 95%CI = 0.25-0.74, pc = 0.006). The latter was associated with a lower LPS-stimulated-PBM IL-1beta secretion. Results suggest that IL-1beta polymorphism influences the susceptibility to acquire SLE in our population. The protective association might be explained by the observed inhibitory effect of IL-1beta + 3953T allele on the secretion of IL-1beta under inflammatory circumstances.
15256380 Inhibition of TNF alpha during maturation of dendritic cells results in the development of 2005 Mar BACKGROUND: Dendritic cells orchestrate pivotal immunological processes mediated by the production of cytokines and chemokines. OBJECTIVE: To assess whether neutralisation of tumour necrosis factor alpha (TNF alpha) during maturation of dendritic cells affects their phenotype and behaviour, which might explain the beneficial effects of TNF alpha neutralisation in rheumatoid arthritis. METHODS: Immature and fully matured dendritic cells were cultured from blood monocytes from patients with rheumatoid arthritis and healthy controls following standardised protocols. TNF alpha was neutralised by addition of the p55 soluble TNF alpha receptor, PEGsTNFRI. The effect of TNF alpha neutralisation on the phenotype (CD14, CD16, CD32, CD64, CD80, CD83, CD86, and MHC) of dendritic cells was investigated by flow cytometry. Expression of chemokines (CCL17, CCL18, CCL19, CCL22, CCL3, and CXCL8) and production of IL1 beta and IL6 during dendritic cell differentiation and maturation were examined. RESULTS: Neutralisation of TNF alpha during the differentiation and maturation of dendritic cells did not result in an altered dendritic cell phenotype in the rheumatoid patients or the healthy controls. In contrast, the expression of CCL17, CCL18, CCL19, CCL22, CCL3, and CXCL8 by dendritic cells was significantly reduced when TNF alpha activity was inhibited during lipopolysaccharide triggered dendritic cell maturation. The production of IL1 beta and IL6 by mature dendritic cells was inhibited by PEGsTNFRI. CONCLUSIONS: Inhibition of TNF alpha activity during dendritic cell maturation leads to the development of semi-mature cells. These data suggest a novel pathway by which the neutralisation of TNF alpha might exert its therapeutic effects.