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Lars Klareskog

Publications and source records attributed to Lars Klareskog.

At least 19 recordsLinked to original sources
PubMed2007

Smoking as a trigger for inflammatory rheumatic diseases.

PURPOSE OF REVIEW: This review has two purposes: to describe the known effects of cigarette smoking on the development of inflammatory rheumatic diseases, in particular rheumatoid arthritis and systemic lupus erythematosus, and to review recent research aimed at understanding the mechanisms by which smoking may interact with genes and immunity in triggering these diseases. RECENT FINDINGS: Large case-control studies as well as cohort studies have demonstrated that cigarette smoking is a risk factor for RF positive and anti-citrulline antibody with rheumatoid arthritis and that the risk diminishes only several years after cessation of smoking. Evidence exists that smoking is a risk factor also for systemic lupus erythematosus, and that the risk may be related to the presence of anti-dsDNA antibodies. Mechanistic studies are reviewed that suggest that smoking can trigger specific and potentially disease-inducing immune reactions against citrullinated proteins in rheumatoid arthritis, and dsDNA in systemic lupus erythematosus, and it is suggested that the genetic context determines which immune reactions may be triggered by smoking. SUMMARY: Counselling against smoking should be mandatory in rheumatological practice both to patients and to their relatives. Studies on the mechanisms whereby smoking triggers rheumatoid arthritis and systemic lupus erythematosus may provide fundamental new knowledge about the cause and molecular pathogenesis of these diseases.

Antibodies, Antinuclear↗
PubMed2006

Treatment with rituximab affects both the cellular and the humoral arm of the immune system in patients with SLE.

Herein we investigated how rituximab-induced B cell depletion affected leukocyte subpopulations and antibody titers in SLE patients. We focused our analysis on time points related to absence and return of B cells after depletion. A correlation was found between the baseline frequency and time to repopulation; the fewer B cells initially, the longer to their return. While the few B cells remaining after treatment were of memory, double-negative (IgD-CD27-), and CD5+ phenotype, the returning B cells were mainly naïve, indicating de novo production of B cells. Serum levels of IgG and antibodies against Ro52, Ro60, La44, measles and tetanus remained unchanged, while decreases in IgM, IgE, anti-dsDNA and anti-C1q antibodies were observed. Additionally, a significant increase in activated CD4+ and CD8+ T cells, as well as CD25bright FOXP3+ regulatory T cells was observed. In conclusion, both the humoral and the cellular immune systems were affected by treatment with rituximab.

Antibodies, Monoclonal↗
PubMed2006

Genes, environment and immunity in the development of rheumatoid arthritis.

The combined role of genes, environment and immunity in the development of rheumatoid arthritis (RA) has been the subject of recent investigations. New data support a gene-environment interaction between smoking and the MHC class II HLA-DRB1 shared epitope (SE) genes in anti-citrulline antibody (anti-CP(+)) RA but not in anti-CP(-) disease. These data from genetic epidemiology, together with information on citrullination in the lungs of smokers, have prompted the formulation of a new etiological hypothesis for anti-CP(+) RA, suggesting that smoking in the context of HLA-DR SE might trigger immunity to citrulline-modified proteins and that this immunity, after several years, might cause arthritis.

Animals↗
PubMed2006

Sulphasalazine inhibits human antigen-specific immune responses in vivo.

OBJECTIVE: To study the effects of the antirheumatic drug sulphasalazine (SASP) on the immune system by analysing systemic and gut-associated immune responses. METHODS: A total of 23 healthy volunteers were treated with either SASP or placebo for 5 weeks in a double-blind fashion and immunised 2 weeks after the initiation of treatment. Specific immune responses were triggered by subcutaneous immunisation with tetanus toxoid and by peroral immunisation with inactivated influenza vaccine. The effects of treatment on specific immunity to tetanus and influenza were evaluated by enzyme-linked immunospot assay quantifying the number of circulating specific and total antibody-producing cells (spot-forming cells (SFC)) at 6, 8 and 10 days after immunisation. RESULTS: An immunosuppressive effect of SASP on systemic immune response was observed with a decrease in the total number of IgG-SFC, IgG anti-tetanus SFC and IgG anti-tetanus antibody levels in serum. SASP also exerted an immunosuppressive effect on the mucosa-associated immune system as seen from its down-regulating effect on the total number of circulating IgA SFC. CONCLUSIONS: These data show firstly that SASP exerts an immunosuppressive effect on defined immune responses to immunisation in vivo, and secondly that both mucosa-associated and systemic immunity are affected by SASP treatment.

Adolescent↗
PubMed2006

The inflammatory reflex and risk for rheumatoid arthritis: a case-control study of human vagotomy.

Recent data suggest remarkable effects of vagus stimulation (reduction) and vagotomy (exacerbation) on acute inflammation in rats, the so-called "inflammatory reflex". Its role in humans remains unknown. Therefore, the aim was to explore whether surgical vagotomy in humans would affect the risk of a prototype inflammatory disease, rheumatoid arthritis. This was a case-control study. Assessment of the relative risk (RR) of developing rheumatoid arthritis after surgical vagotomy during 1964-2001 in 63,092 prevalent rheumatoid arthritis cases versus 125,404 matched controls from the general population and in 2548 incident rheumatoid arthritis cases versus 24,357 matched controls from the general population, respectively, was done. For comparison, we assessed RRs for hospitalisation for gastric disorders not including vagotomy. Data on exposures and rheumatoid arthritis were retrieved from population-based and prospectively recorded Swedish registers. A pre-rheumatoid arthritis vagotomy was not significantly associated with an increased risk for rheumatoid arthritis (RR = 1.17, 95% CI 0.97 to 1.40). RRs in the same range were observed for several other pre-rheumatoid arthritis gastric conditions that do not include vagotomy (eg, gastric ulcer RR = 1.21, 95% 1.11 to 1.33). Vagotomy has no specific effect on the risk of developing rheumatoid arthritis in humans. Gastroduodenal ulcers occur more often than expected even before the occurrence of rheumatoid arthritis.

Adolescent↗
PubMed2006

European population substructure: clustering of northern and southern populations.

Using a genome-wide single nucleotide polymorphism (SNP) panel, we observed population structure in a diverse group of Europeans and European Americans. Under a variety of conditions and tests, there is a consistent and reproducible distinction between "northern" and "southern" European population groups: most individual participants with southern European ancestry (Italian, Spanish, Portuguese, and Greek) have >85% membership in the "southern" population; and most northern, western, eastern, and central Europeans have >90% in the "northern" population group. Ashkenazi Jewish as well as Sephardic Jewish origin also showed >85% membership in the "southern" population, consistent with a later Mediterranean origin of these ethnic groups. Based on this work, we have developed a core set of informative SNP markers that can control for this partition in European population structure in a variety of clinical and genetic studies.

Arthritis, Rheumatoid↗
PubMed2006

Variability in synovial inflammation in rheumatoid arthritis investigated by microarray technology.

In recent years microarray technology has been used increasingly to acquire knowledge about the pathogenic processes involved in rheumatoid arthritis. The present study investigated variations in gene expression in synovial tissues within and between patients with rheumatoid arthritis. This was done by applying microarray technology on multiple synovial biopsies obtained from the same knee joints. In this way the relative levels of intra-patient and inter-patient variation could be assessed. The biopsies were obtained from 13 different patients: 7 by orthopedic surgery and 6 by rheumatic arthroscopy. The data show that levels of heterogeneity varied substantially between the biopsies, because the number of genes found to be differentially expressed between pairs of biopsies from the same knee ranged from 6 to 2,133. Both arthroscopic and orthopedic biopsies were examined, allowing us to compare the two sampling methods. We found that the average number of differentially expressed genes between biopsies from the same patient was about three times larger in orthopedic than in arthroscopic biopsies. Using a parallel analysis of the tissues by immunohistochemistry, we also identified orthopedic biopsies that were unsuitable for gene expression analysis of synovial inflammation due to sampling of non-inflamed parts of the tissue. Removing these biopsies reduced the average number of differentially expressed genes between the orthopedic biopsies from 455 to 171, in comparison with 143 for the arthroscopic biopsies. Hierarchical clustering analysis showed that the remaining orthopedic and arthroscopic biopsies had gene expression signatures that were unique for each patient, apparently reflecting patient variation rather than tissue heterogeneity. Subsets of genes found to vary between biopsies were investigated for overrepresentation of biological processes by using gene ontology. This revealed representative 'themes' likely to vary between synovial biopsies affected by inflammatory disease.

Aged↗
PubMed2006

Anti-tumor necrosis factor therapy increases synovial osteoprotegerin expression in rheumatoid arthritis.

OBJECTIVE: Treatment of rheumatoid arthritis (RA) with tumor necrosis factor (TNF)-blocking agents, including etanercept and infliximab, has resulted in reductions in the radiographic progression of RA. However, the exact mechanism by which this protection occurs has not been determined. In order to add to such knowledge, we investigated the effect of anti-TNF therapy on the expression of osteoprotegerin (OPG) and receptor activator of NF-kappaB ligand (RANKL) in synovial tissue. METHODS: The expression of OPG and RANKL in synovial biopsy specimens was evaluated by immunohistochemistry. Serial synovial biopsy specimens were obtained from 18 patients with RA, before and after treatment with etanercept (9 patients) or infliximab (9 patients). Biopsy specimens were evaluated by double-blind semiquantitative analysis and image analysis. The in vitro effect of TNF antagonists on the RANKL/OPG expression in osteoblasts and endothelial cells was evaluated by Western blotting. Statistical analysis was performed using Wilcoxon's signed rank test, followed by the Bonferroni correction for multiple comparisons of paired samples. The results of in vitro experiments were evaluated by one-way analysis of variance, with Tukey's post hoc test. RESULTS: Treatment with both infliximab and etanercept increased the expression of OPG in synovial tissue. After 8 weeks of treatment, neither infliximab nor etanercept influenced RANKL expression. In both groups of patients, the RANKL:OPG ratio decreased following therapy. In vitro, both of the TNF antagonists mimicked the in vivo effect, inducing a decrease in the RANKL:OPG ratio in TNF-primed osteoblasts and endothelial cells. CONCLUSION: Therapy with TNF antagonists in RA modulates the OPG/RANKL system, a potential mechanism that could explain the retardation of radiographic damage observed following anti-TNF therapy.

Adult↗
PubMed2006

A new model for an etiology of rheumatoid arthritis: smoking may trigger HLA-DR (shared epitope)-restricted immune reactions to autoantigens modified by citrullination.

OBJECTIVE: To investigate whether smoking and HLA-DR shared epitope (SE) genes may interact in triggering immune reactions to citrulline-modified proteins. METHODS: In a case-control study involving patients with recent-onset rheumatoid arthritis (RA), we studied interactions between a major environmental risk factor (smoking), major susceptibility genes included in the SE of HLA-DR, and the presence of the most specific autoimmunity known for RA (i.e., antibodies to proteins modified by citrullination). Immunostaining for citrullinated proteins in cells from bronchoalveolar lavage fluid was used to investigate whether smoking is associated with citrullination in the lungs. RESULTS: Previous smoking was dose-dependently associated with occurrence of anticitrulline antibodies in RA patients. The presence of SE genes was a risk factor only for anticitrulline-positive RA, and not for anticitrulline-negative RA. A major gene-environment interaction between smoking and HLA-DR SE genes was evident for anticitrulline-positive RA, but not for anticitrulline-negative RA, and the combination of smoking history and the presence of double copies of HLA-DR SE genes increased the risk for RA 21-fold compared with the risk among nonsmokers carrying no SE genes. Positive immunostaining for citrullinated proteins was recorded in bronchoalveolar lavage cells from smokers but not in those from nonsmokers. CONCLUSION: We identified an environmental factor, smoking, that in the context of HLA-DR SE genes may trigger RA-specific immune reactions to citrullinated proteins. These data thus suggest an etiology involving a specific genotype, an environmental provocation, and the induction of specific autoimmunity, all restricted to a distinct subset of RA.

Adolescent↗
PubMed2006

Comparison of etanercept and methotrexate, alone and combined, in the treatment of rheumatoid arthritis: two-year clinical and radiographic results from the TEMPO study, a double-blind, randomized trial.

OBJECTIVE: To evaluate the efficacy, including radiographic changes, and safety of etanercept and methotrexate (MTX), used in combination and alone, in patients with rheumatoid arthritis (RA) in whom previous treatment with a disease-modifying antirheumatic drug other than MTX had failed. METHODS: Patients with RA were treated with etanercept (25 mg subcutaneously twice weekly), oral MTX (up to 20 mg weekly), or combination therapy with etanercept plus MTX through a second year, in a double-blinded manner. Clinical response was assessed using American College of Rheumatology (ACR) criteria and the Disease Activity Score (DAS), in a modified intent-to-treat analysis with the last observation carried forward (LOCF) and in a population of completers. Radiographs of the hands, wrists, and forefeet were scored for erosions and joint space narrowing at annual intervals. RESULTS: A total of 503 of 686 patients continued into year 2 of the study. During the 2 years, significantly fewer patients receiving combination therapy withdrew from the study (29% of the combination therapy group, 39% of the etanercept group, and 48% of the MTX group). Both the LOCF and the completer analyses yielded similar results. The ACR 20% improvement (ACR20), ACR50, and ACR70 responses and the remission rates (based on a DAS of <1.6) were significantly higher with combination therapy than with either monotherapy (P<0.01). Similarly, improvement in disability (based on the Health Assessment Questionnaire) was greater with combination therapy (P<0.01). The combination therapy group showed significantly less radiographic progression than did either group receiving monotherapy (P<0.05); moreover, radiographic progression was significantly lower in the etanercept group compared with the MTX group (P<0.05). For the second consecutive year, overall disease progression in the combination therapy group was negative, with the 95% confidence interval less than zero. Adverse events were similar in the 3 treatment groups. CONCLUSION: Etanercept in combination with MTX reduced disease activity, slowed radiographic progression, and improved function more effectively than did either monotherapy over a 2-year period. No increase in toxicity was associated with combination treatment with etanercept plus MTX.

Antirheumatic Agents↗
PubMed2006

Association of chronic inflammation, not its treatment, with increased lymphoma risk in rheumatoid arthritis.

OBJECTIVE: Chronic inflammatory conditions such as rheumatoid arthritis (RA) have been associated with malignant lymphomas. This study was undertaken to investigate which patients are at highest risk, and whether antirheumatic treatment is hazardous or protective. METHODS: We performed a matched case-control study of 378 consecutive Swedish RA patients in whom malignant lymphoma occurred between 1964 and 1995 (from a population-based RA cohort of 74,651 RA patients), and 378 controls. Information on disease characteristics and treatment from onset of RA until lymphoma diagnosis was abstracted from medical records. Lymphoma specimens were reclassified and tested for Epstein-Barr virus (EBV). Relative risks (odds ratios [ORs]) for lymphomas (by subtype) associated with deciles of cumulative disease activity were assessed, as were ORs associated with drug treatments. RESULTS: The relative risks of lymphoma were only modestly elevated up to the seventh decile of cumulative disease activity. Thereafter, the relative risk increased dramatically (OR ninth decile 9.4 [95% confidence interval 3.1-28.0], OR tenth decile 61.6 [95% confidence interval 21.0-181.0]). Most lymphomas (48%) were of the diffuse large B cell type, but other lymphoma subtypes also displayed an association with cumulative disease activity. Standard nonbiologic treatments did not increase lymphoma risk. EBV was present in 12% of lymphomas. CONCLUSION: Risk of lymphoma is substantially increased in a subset of patients with RA, those with very severe disease. High inflammatory activity, rather than its treatment, is a major risk determinant.

Adolescent↗
PubMed2006

Intraarticular corticosteroids decrease synovial RANKL expression in inflammatory arthritis.

OBJECTIVE: Intraarticular corticosteroids are frequently used as successful adjuvant therapy for inflammatory arthritides, but little is known about their effects on molecules that regulate bone biology. We undertook this study to investigate the effect of intraarticular corticosteroids on the synovial expression of RANKL and osteoprotegerin (OPG). METHODS: We evaluated RANKL, OPG, and surface marker expression by immunohistochemical methods in synovial knee biopsy samples obtained from 13 patients with inflammatory arthritis before and 2 weeks following intraarticular injection of triamcinolone hexacetonide. We further investigated the effect of dexamethasone (DEX) on RANKL expression by lymphocytes from rheumatoid arthritis synovial fluids (RA SF), using flow cytometric analysis. Finally, we evaluated the in vitro effect of DEX on RANKL and OPG expression in osteoblast-like cells, by Western blotting. RESULTS: Intraarticular corticosteroids induced a decrease in the number of synovial T cells without influencing the number of macrophages, evaluated as both CD68+ and CD163+ cells. This change was paralleled by a decrease of synovial RANKL expression with a concomitant reduction of the RANKL:OPG ratio. DEX down-regulated RANKL expression on lymphocytes derived from RA SF. Moreover, in vitro pretreatment of osteoblast-like cells with tumor necrosis factor favored an antiresorptive effect of DEX treatment through a similar down-regulation of RANKL expression. CONCLUSION: The decrease in inflammation attributed to intraarticular corticosteroids is accompanied by down-modulation of bone destruction markers. These findings offer a rationale for the beneficial effect of corticosteroids on joint erosion in arthritis.

Adrenal Cortex Hormones↗
PubMed2006

Disconnect between inflammation and joint destruction after treatment with etanercept plus methotrexate: results from the trial of etanercept and methotrexate with radiographic and patient outcomes.

OBJECTIVE: To determine the relationship between disease activity and radiographic progression of joint destruction in patients with rheumatoid arthritis (RA) treated with methotrexate (MTX), those treated with etanercept, and those treated with the combination of MTX plus etanercept. METHODS: Baseline, 12-month, and 24-month data from the Trial of Etanercept and Methotrexate with Radiographic and Patient Outcomes database were analyzed. The dependent variable was the 1-year change in the modified Sharp/van der Heijde score (Sharp score); therefore, 2 interval changes per patient were available. Interval change in the Sharp score was modeled by time (years), treatment, disease activity, and the interaction (disease activity x treatment). Disease activity was reflected by the time-averaged Disease Activity Score (taDAS) and the time-averaged C-reactive protein (taCRP) level, which were calculated per 1-year interval. Generalized mixed linear modeling (GMLM) was used to adjust for within-patient correlation. RESULTS: GMLM confirmed a significant interaction between treatment and the taCRP level and taDAS with respect to the change in Sharp score (P = 0.012 and P = 0.03, respectively). In patients treated with MTX alone, radiographic progression increased with an increasing taCRP level or taDAS, although progression rates were low in patients whose disease was in remission and in those with low-to-moderate disease activity. This relationship was less clear in patients treated with etanercept and was absent in those who received combination therapy. CONCLUSION: Combination therapy with MTX plus etanercept uncouples the classic relationship between disease activity and radiographic progression in patients with RA.

Antirheumatic Agents↗
PubMed2006

Characteristics of diffuse large B cell lymphomas in rheumatoid arthritis.

OBJECTIVE: Patients with rheumatoid arthritis (RA) are at increased risk of malignant lymphomas, with a correlation between RA disease severity and lymphoma risk, most pronounced for diffuse large B cell lymphomas (DLBCLs), which also constitute the majority of RA-associated lymphomas. DLBCLs can be further subdivided into germinal center (GC)-like and non-GC-like subtypes, with different cellular origins and prognoses. This study was undertaken to investigate whether RA displays a specific association with any of the DLBCL subtypes. METHODS: We identified 139 patients with DLBCLs within a population-based case-control study of 378 RA patients with lymphoma. The DLBCLs were examined for CD10, Bcl-6, and interferon regulatory factor 4 expression patterns, subclassified into GC and non-GC subtypes, and then correlated with clinical parameters. RESULTS: We found a statistically significant predominance of the non-GC subtype (97 patients; 70% of all DLBCLs). These patients more often had an advanced stage of lymphoma at diagnosis and had a worse 5-year overall survival rate (16% versus 33%) compared with patients with the GC subtype. There was a strong association with RA disease activity in both subtypes, with >70% of the GC and non-GC cases occurring in RA patients with the highest overall disease activity scores. CONCLUSION: These findings suggest that severe RA is particularly associated with the non-GC subtype of DLBCL, and indicate a critical role of activated peripheral B cells as the cells of origin in these lymphomas.

Adolescent↗
PubMed2006

Mechanisms of disease: Genetic susceptibility and environmental triggers in the development of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a complex disease in which environmental agents are thought to interact with genetic factors that influence susceptibility. This interaction triggers immunologic events that eventually result in the clinical signs of arthritis. Knowledge of the chain of etiological events that lead to the development of RA is incomplete. In this review, we describe the experimental approaches that are used to address the issue of gene-environment interactions in the etiology of RA, and discuss relevant examples of such interactions. We focus on how smoking, the best-known environmental risk factor for RA, interacts with HLA-DR shared epitope genes, the main genetic risk factors for RA, and result in a high risk of RA in individuals exposed to both of these risk factors. From these and other related findings, we can begin to define the distinct environmental risk factors (such as smoking) that in certain genetic contexts (for example, the presence of HLA-DR shared epitope alleles) can trigger immune reactions (such as autoantibodies to citrullinated peptides) many years before onset of RA, and consider how these immune reactions might contribute to clinical symptoms in a subset of affected patients. Increased knowledge about these and other events involved in the development of RA should enable the design of new tools for suppressing RA pathogenesis before the onset of disease.

Arthritis, Rheumatoid↗
PubMed2006

Synovial expression of IL-15 in rheumatoid arthritis is not influenced by blockade of tumour necrosis factor.

Blockade of tumour necrosis factor (TNF) is an effective treatment in rheumatoid arthritis (RA), but both non-responders and partial responders are quite frequent. This suggests that other pro-inflammatory cytokines may be of importance in the pathogenesis of RA and as possible targets for therapy. In this study we investigated the effect of TNF blockade (infliximab) on the synovial expression of IL-15 in RA in relation to different cell types and expression of other cytokines, to elucidate whether or not IL-15 is a possible target for therapy, independently of TNF blockade. Two arthroscopies with multiple biopsies were performed on nine patients with RA and knee-joint synovitis before and after three infusions of infliximab (3 mg/kg). Synovial biopsies were analysed with immunohistochemistry for expression of IL-15, TNF, IL-1alpha, IL-1ss and IFN-gamma, and for the cell surface markers CD3, CD68 and CD163. Stained synovial biopsy sections were evaluated by computerized image analysis. IL-15 expression was detected in all synovial biopsies taken at baseline. After infliximab therapy, the expression of IL-15 was increased in four patients and reduced in five. Synovial expression of IL-15 was not correlated with any CD marker or with the presence of any other cytokine. Synovial cellularity was decreased after 8 to 10 weeks of treatment with a significant reduction of the CD68-positive synovial cells, whereas no significant change was seen in the number of CD3-positive T cells and CD163-expressing macrophages. The number of TNF-producing cells in the synovial tissue at baseline was correlated with a good response to therapy. Thus, in this study the synovial expression of IL-15 in RA was not consistently influenced by TNF blockade, being apparently independent of TNF expression in the synovium. Consequently, we propose that IL-15 should remain as a therapeutic target in RA, regardless of the response to TNF blockade.

Antibodies, Monoclonal↗
PubMed2006

Effect of infliximab on mRNA expression profiles in synovial tissue of rheumatoid arthritis patients.

We examined the gene expression profiles in arthroscopic biopsies retrieved from 10 rheumatoid arthritis patients before and after anti-TNF treatment with infliximab to investigate whether such profiles can be used to predict responses to the therapy, and to study effects of the therapy on the profiles. Responses to treatment were assessed using European League Against Rheumatism response criteria. Three patients were found to be good responders, five patients to be moderate responders and two patients to be nonresponders. The TNF-alpha status of the biopsies from each of the patients before treatment was also investigated immunohistochemically, and it was detected in biopsies from four of the patients, including all three of the good responders. The gene expression data demonstrate that all patients had unique gene expression signatures, with low intrapatient variability between biopsies. The data also revealed significant differences between the good responding and nonresponding patients (279 differentially expressed genes were detected, with a false discovery rate < 0.025). Among the identified genes we found that MMP-3 was significantly upregulated in good responders (log2 fold change, 2.95) compared with nonresponders, providing further support for the potential of MMP-3 as a marker for good responses to therapy. An even more extensive list of 685 significantly differentially expressed genes was found between patients in whom TNF-alpha was found and nonresponders, indicating that TNF-alpha could be an important biomarker for successful infliximab treatment. Significant differences were also observed between biopsies taken before and after anti-TNF treatment, including 115 differentially expressed genes in the good responding group. Interestingly, the effect was even stronger in the group in which TNF-alpha was immunohistochemically detected before therapy. Here, 1,058 genes were differentially expressed, including many that were novel in this context (for example, CXCL3 and CXCL14). Subsequent Gene Ontology analysis revealed that several 'themes' were significantly over-represented that are known to be affected by anti-TNF treatment in inflammatory tissue; for example, immune response (GO:0006955), cell communication (GO:0007154), signal transduction (GO:0007165) and chemotaxis (GO:0006935). No genes reached statistical significance in the moderately responding or nonresponding groups. In conclusion, this pilot study suggests that further investigation is warranted on the usefulness of gene expression profiling of synovial tissue to predict and monitor the outcome of rheumatoid arthritis therapies.

Adult↗