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ID PMID Title PublicationDate abstract
15899046 Anti-Sa antibodies and antibodies against cyclic citrullinated peptide are not equivalent 2005 The prognostic value of two antibodies targeting citrullinated antigens, anti-Sa and anti-cyclic citrullinated peptide (CCP), present at inclusion, was evaluated prospectively in a cohort of 165 consecutive patients with recent-onset or early polyarthritis (EPA) followed for up to 30 months. Patients were treated according to current Good Clinical Practice standards. Predefined outcomes were severe arthritis and persistent arthritis. At inclusion, a median of 3 months after disease onset, 133 (81%) patients fulfilled at least four American College of Rheumatology criteria for rheumatoid arthritis and 30 (18%) had erosive changes on radiographs of hands and feet. Disease-modifying anti-rheumatic drugs were used in close to 80% of the patients at 30 months. Joint damage increased linearly over time, whereas disease activity declined markedly and remained low at each follow-up. Autoantibodies were identified in 76 (46%) patients: rheumatoid factor (RF) in 68 (41%), anti-CCP in 53 (33%), and anti-Sa in 46 (28%). All three antibodies were correlated, but anti-Sa antibodies best predicted severity at 18 and 30 months. RF and anti-CCP performed less well. For both outcomes, anti-Sa alone performed better than any combination of antibodies. The presence of any autoantibody identified about 50 to 60% of the patients with poor outcomes. In multivariate analysis, anti-Sa (odds ratio (OR) 8.83), the presence of erosions at inclusion (OR 3.47) and increasing age (OR 1.06/year) were significantly associated with severity, whereas RF and anti-CCP were not significant predictors. Persistent arthritis was present in up to 84% of patients; autoantibodies were specific but poorly sensitive predictors of this outcome. We conclude that assays for antibodies against citrullinated antigens differ in their ability to predict poorer outcomes in patients with EPA. In our EPA cohort treated in accordance with current standards, detection of anti-Sa but not of RF or anti-CCP antibodies, in combination with clinical and radiological variables present at the first encounter, allowed the identification of a subgroup of EPA patients suffering more rapid and more severe joint damage over 30 months.
15903021 TNF-alpha -308 promoter polymorphism in patients with rheumatoid arthritis. 2005 OBJECTIVES: Rheumatoid arthritis (RA) is a chronic inflammatory disease in which tumour necrosis factor-alpha (TNF-alpha) plays an important role. There are, however, controversial reports that TNF-alpha promoter polymorphism may be an independent marker of susceptibility and severity of RA. The aim of the present study was to examine the TNF-alpha -308 promoter polymorphism in patients with RA. METHODS: We examined 91 patients with RA diagnosed according to the criteria of the American College of Rheumatology. Polymerase chain reaction (PCR) amplification was used for analysis of the polymorphism at position -308 in promoter of TNF-alpha gene. RESULTS: Distribution of TNF-alpha genotypes in RA patients did not differ from that in control subjects. Moreover, there was no association between TNF-alpha genotypes and age at disease diagnosis, disease activity in global physician's assessment, and joint and extra-articular involvement. There was also no correlation between TNF-alpha polymorphism and disease activity measures, including erythrocyte sedimentation rate (ESR), CRP, number of swollen and tender joints, and morning stiffness duration. CONCLUSIONS: We suggest that TNF-alpha -308 promoter polymorphism is not a genetic risk factor for RA susceptibility and severity.
15713218 Analysis of the functional NFKB1 promoter polymorphism in rheumatoid arthritis and systemi 2005 Feb Nuclear factor (NF)-kappaB plays an important role in inflammatory diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). A functional insertion/deletion polymorphism (-94ins/delATTG) has been identified in the promoter of the NFKB1 gene. In addition, a polymorphic dinucleotide repeat (CA) has been identified in proximity to the coding region of the human NFKB1 gene. The aim of the present study was to investigate the influence of both the -94ins/delATTG and the (CA) microsatellite NFKB1 polymorphisms in the susceptibility/severity of RA and SLE. We analyzed the distribution of -94ins/delATTG and the multiallelic (CA)(n) repeat in 272 RA patients, 181 SLE patients, and 264 healthy controls from Southern Spain, in both cases using a polymerase chain reaction-fluorescent method. No statistically significant difference in the distribution of the -94delATTG NFKB1 genotypes and alleles between RA patients, SLE patients, and control subjects was observed. Similarly, we found no statistically significant differences in the (CA)(n) microsatellite allele frequency between controls and RA patients or SLE patients. In addition, no association was found between the above mentioned NFKB1 polymorphisms with any of the demographic and clinical parameters tested either in RA or in SLE patients. From these results, it seems that the -94ins/delATTG and the (CA)(n) repeat of NFKB1 gene may not play a relevant role in RA and/or SLE in our population.
16207317 Expression and functional properties of antibodies to tissue inhibitors of metalloproteina 2005 Tissue inhibitors of matrix metalloproteinases (TIMPs) regulate the breakdown of extracellular matrix components and play an important role in tissue remodelling and growth, in both physiological and pathological conditions. We studied the autoimmune response to TIMPs in patients with rheumatoid arthritis (RA). Eighty-nine paired blood and synovial fluid samples from patients with RA were assessed for their reactivity with recombinant tissue inhibitors of metalloproteinases (TIMPs) 1 to 4 by an ELISA and were compared with blood from 62 healthy controls and 21 synovial fluid samples from patients with degenerative joint diseases. Presence of antibodies was established as the absorbance of the sample more than 2 standard deviations above the mean of the controls. In addition, immunoglobulin G (IgG) from blood samples of RA patients possessing TIMP antibodies was isolated on protein A-sepharose and tested for the in vitro ability to neutralize TIMP-2-dependent effects on metalloproteinase 9 (MMP9). Anti-TIMP antibodies were found in 56% of RA samples but in only 5% of the controls (P < 0.005). RA patients had high frequencies of antibodies against all TIMPs except TIMP-3. TIMP-2 antibodies were most frequently found (33%), being significantly more prevalent (P = 0.024) in patients with nonerosive than erosive RA. TIMP-1 antibodies were significantly more often found in synovial fluid samples than in the matched blood samples (P < 0.025). Importantly, the IgG fraction containing TIMP antibodies down-regulated the TIMP-2 inhibitory effect, thereby supporting MMP9 activity in vitro. In the present study, we show that RA patients frequently develop autoimmune response to TIMPs that may act as a functionally significant regulator of MMP activity and thereby of joint destruction.
16934964 The metabolic syndrome, omega-3 fatty acids and inflammatory processes in relation to schi 2006 Oct Although schizophrenia is normally regarded as a brain disease, there is clear evidence that schizophrenia is strongly associated with a variety of physical conditions. These include an increased rate of the metabolic syndrome and its physical complications including diabetes and coronary heart disease, and a reduced rate of rheumatoid arthritis. It is argued that these associations may point to a commonality of some aetiological factors. Evidence implicating omega-3 fatty acids in all of these disorders is presented. The associations may derive either from genetic or from environmental factors, including nutrition. Further investigation of these associations may give important clues regarding the aetiology of schizophrenia.
15853438 Modelling cost effectiveness and cost utility of sequential DMARD therapy including leflun 2005 OBJECTIVE: To estimate the 3-year incremental cost effectiveness and cost utility of introducing leflunomide into sequential therapy, consisting of the most frequently used disease-modifying antirheumatic drugs (DMARDs), for patients with rheumatoid arthritis in specialised, i.e. rheumatological, care in Germany. DESIGN AND SETTING: The analysis was conducted from the societal perspective in Germany using an existing 3-year simulation model, which was adapted to the German healthcare system after secondary analysis of relevant publications and data. DMARD sequences including leflunomide were compared with those excluding leflunomide. Costs comprised direct costs incurred by treatment and indirect costs incurred by loss of productivity (sick leave and premature retirement) of rheumatoid arthritis patients. Effectiveness parameters were given by response years gained (RYGs) according to the American College of Rheumatology (ACR) criteria for 20%, 50% and 70% improvement (ACR20/50/70RYGs) and by QALYs gained (QALYGs). Costs, effects and QALYs were discounted by 5% per annum. In the base-case analysis, average values of costs, response years and QALYs were applied. Costs were in 1998-2001 values (euro 1 approximately equal to $US 0.91, average of the period from the year 2000 through 2001). MAIN OUTCOME MEASURES AND RESULTS: After 3 years, adding leflunomide was less costly and more effective than the strategy excluding leflunomide when total (direct and indirect) costs were considered. There were savings of euro 271,777 and 8.1, 4.3, 5.1 and 4.9 ACR20RYGs, ACR50RYGs, ACR70RYGs and QALYGs per 100 patients, respectively, obtained through adding leflunomide. Focusing on direct costs, adding leflunomide was more costly and more effective compared with excluding leflunomide, with an incremental cost effectiveness of euro 5004 per ACR20RYG, euro 9535 per ACR50RYG, euro 7996 per ACR70RYG, and an incremental cost utility of euro8301 per QALYG, after 3 years. The robustness of the results was shown in comprehensive sensitivity analyses. In the analysis of extremes, different combinations of the limits of cost, effectiveness and utility parameters were investigated. Adding leflunomide to sequential DMARD therapy remained dominant in 79% of the possible cases, i.e. was less costly and more effective than the strategy excluding leflunomide. Focusing on direct costs, adding leflunomide became dominant in 29% and remained more costly and more effective in 50% of possible cases. CONCLUSIONS: Our analysis suggests, with its underlying data and assumptions, that having leflunomide as an additional option in a DMARD treatment sequence extends the time patients benefit from DMARD therapy at reasonable additional direct costs. Adding leflunomide may even be cost saving when total (direct and indirect) costs are considered. As data on DMARD effectiveness were extracted from the results of clinical trials, real-world data from observational studies would be needed to corroborate the findings of the present analysis.
16197363 Meloxicam: a reappraisal of pharmacokinetics, efficacy and safety. 2005 Oct The discovery of two distinct isoenzymes of COX has led to the development and clinical introduction of COX-2 inhibitors with increased selectivity onto the market. Meloxicam is a non-steroidal anti-inflammatory drug (NSAID) of the oxicam class, and is a preferential inhibitor of COX-2, demonstrating effectiveness with anti-inflammatory, analgesic and antipyretic activity. Meloxicam is therapeutically utilised in the management of osteoarthritis and rheumatoid arthritis. Trials have examined the risk of gastrointestinal ulceration of meloxicam when compared with traditional non-specific COX-inhibiting NSAIDs with mixed results; meloxicam seems to have a greater gastrointestinal risk than the highly specific COX-2 NSAIDs. Meloxicam has a plasma half-life of approximately 20 h and is convenient for once daily administration. Neither moderate renal nor hepatic insufficiency significantly alters the pharmacokinetics of meloxicam in short-term studies. Furthermore, dose adjustment is not required in the elderly. Recent drug-drug interaction studies have demonstrated that meloxicam interacts with some medications, including cholestyramine, lithium and some inhibitors of cytochrome P450 -2C9 and -3A4. Consequently, increased clinical vigilance should be maintained when coprescribing some medications with meloxicam. Concentration-dependent therapeutic and toxicological effects have yet to be extensively elucidated for meloxicam. Long-term safety in various organ systems, especially in the heart and vascular system and with concomitant drug administration, remains to be proven. The pharmacokinetics of meloxicam enables once daily application, which increases compliance compared with some shorter acting NSAIDs; however, long-term clinical data clearly demonstrating safety and efficacy advantages are lacking.
16673131 Anemia in rheumatoid arthritis: high prevalence of iron-deficiency anemia in Indian patien 2006 Oct Anemia in rheumatoid arthritis (RA) is multi-factorial. We studied the prevalence and type of anemia and its correlation with disease variables in RA patients. Among patients with RA anemia was defined as hemoglobin
15761726 Laryngeal involvement in rheumatoid arthritis. 2005 Jun Rheumatoid arthritis (RA) is a chronic inflammatory disease affecting the synovial membrane, which causes joint damage and bone destruction. Extra-articular manifestations are numerous, involving multiple organ systems. Rheumatoid nodules are common extra-articular findings occurring in 20% RA patients. They develop most commonly in pressure areas (elbows and finger joints) and may occasionally affect internal organs including pleura, lungs, meninges, larynx, and others. Furthermore, RA affects the ear, nose, and throat, causing various otorhinolaryngological symptoms. In this report we describe two patients with RA and laryngeal involvement, mostly rheumatoid nodule formation, with a review of the literature.
16982199 Anti-inflammatory cytokines in gingival crevicular fluid in patients with periodontitis an 2006 Aug Cytokines which are produced by host cells play an important role in pathogenesis both rheumatoid arthritis (RA) and chronic periodontitis (CP). In this study, we aim to investigate the levels of Interleukin (IL)-4 and IL-10 in gingival crevicular fluid (GCF). Seventeen patients with CP, 17 patients with RA and 17 healthy controls (HC) were included. The RA group was divided into two groups according to gingival sulcus depths (RA-a: PD < or =3mm, (n=12), RA-b: PD>3mm, (n=5)). For each patient, clinical parameters were recorded. The GCF samples were evaluated by enzyme-linked immunosorbent assay (ELISA) for IL-4 and IL-10 levels. IL-4 levels in the RA-a, RA-b and CP subjects were significantly lower compared to the HC subjects (p<0.05). The mean level of IL-4 in RA-b group was significantly higher than that in CP group (p<0.05). IL-10 mean level in the HC group was higher than those in the other groups (p<0.05). In the RA-a group, higher IL-10 level was found compared to the CP patients (p<0.05). Within the limitations of this preliminary report, it can be concluded that the initiation and progression of periodontal inflammation may be due to a lack or inappropriate response of the anti-inflammatory cytokines in both CP and RA.
16583405 Childbearing decisions and family size among women with rheumatoid arthritis. 2006 Apr 15 OBJECTIVE: To estimate childbearing trends relative to age and stage of family development and to report on childbearing decisions among women with rheumatoid arthritis (RA). METHODS: Information about childbearing history and decisions was collected through structured telephone interviews with an existing cohort of married women with RA (n = 411), and was examined according to women's age at RA diagnosis and when RA was diagnosed relative to when children were born. RESULTS: Almost all women (91.2%) reported at least 1 pregnancy; the majority (85.4%) reported at least 1 live birth. The odds of any pregnancy or a live birth were not significantly different according to age at diagnosis; however, women diagnosed at age < or =18 had fewer pregnancies and fewer children. Similarly, women diagnosed with RA prior to the birth of their first child had the fewest pregnancies and children. Few women (8%) reported being advised to limit family size, although approximately 20% reported that RA had affected their childbearing decisions. Being advised to limit family size was associated with fewer pregnancies and fewer children (P < 0.0001). Consideration of RA in childbearing decisions was more common among women diagnosed with RA at an early age. Women who reported that RA affected childbearing decisions were not less likely to have any pregnancy or any children, but had significantly fewer pregnancies and children. CONCLUSION: Lower birth rates among women with RA may at least in part reflect choices by women to limit family sizes. Future research into the link between RA and fertility should take women's childbearing choices into account.
16451202 Levels of the soluble forms of CD80, CD86, and CD83 are elevated in the synovial fluid of 2006 Jan The release of soluble forms of CD80 (sCD80), CD86 (sCD86), and CD83 (sCD83) provide a potentially powerful immunoregulatory mechanism. We therefore investigated the potential presence and relative levels of these molecules in the synovial fluid (SF) and serum of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Serum and SF levels were measured by enzyme-linked immunosorbent assay. Serum levels of sCD80, sCD86, and sCD83 in RA and OA patients were similar to those present in normal donor serum (NDS) and the SF of OA patients. In contrast, when compared with NDS and OA SF levels, almost all RA SF samples had elevated sCD83 levels (32/35, >0.63 ng/ml) and a substantial proportion had elevated sCD80 (13/29, >0.22 ng/ml) or sCD86 (16/33, >2.31 ng/ml) levels. Analysis of matched pairs of serum and SF from RA patients demonstrated that the SF/serum ratio for sCD80 (95% CI = 1.7-3), sCD86 (95% CI = 1.5-3.1), and sCD83 (95% CI = 3.6-7.8) levels was >1 in almost all patients. In conclusion, this study shows that the SF from almost all RA patients contain elevated levels of sCD83 and the majority of these samples also contain elevated levels of sCD80 and/or sCD86. These molecules may play a role in modulating immune responses within the rheumatoid joint.
16400533 Contribution of partner support in self-management of rheumatoid arthritis patients. An ap 2006 Feb The aim of this exploratory study was to test the applicability of a model derived from the Theory of Planned Behavior on self-management. In this model social support from the partner, attitude and self-efficacy are determinants of intention, and intention and self-efficacy are determinants of self-management. We tested the model on rheumatoid arthritis patients who have a partner, using regression analyses and structural equation models. Partner support and attitude partly explained the variance in intention. Intention in turn partly explained the variance in self-management. Self-efficacy showed a tendency to positively affect intention and self-management. The present study provided moderate support for the use of the constructs and ideas derived from the Theory of Planned Behavior-attitude, social support, self-efficacy, and intention-in predicting and explaining self-management.
17039318 Hypersensitivity reaction against influenza vaccine in a patient with rheumatoid arthritis 2006 A 58-year-old Japanese woman with rheumatoid arthritis (RA) suffered from high fever triggered by administration of an influenza vaccine after a 4-month-long effective treatment course with the TNF-alpha inhibitor etanercept. Influenza vaccine had been previously administrated safely to the patient before initiation of etanercept therapy. The fever occurred without other symptoms soon after vaccine administration, progressed to high fever 1 day later, and spontaneously resolved the second day. The clinical course appears to be compatible with drug fever closely associated with immediate hypersensitivity (in particular, late-phase type I allergic reaction), in which T helper (Th) 2 cells play a crucial role. Etanercept can strongly suppress Th1-mediated reactions; therefore, Th2 activity may be augmented by etanercept treatment in aspect of antagonism between Th1 and Th2 mechanisms. In RA patients who receive treatment with TNF-alpha inhibitor such as etanercept, activation of Th2-mediated immune responses such as immediate hypersensitivity may be a necessary side effect for those who receive vaccinations.
15971994 New therapeutic approaches for rheumatoid arthritis. 2005 Jun Rheumatoid arthritis (RA) is a chronic polyarthritis leading to joint destruction and remarkable disability. Current therapies have various degrees of efficacy, but toxicity frequently limits their long-term use. Although the etiology of the disease remains unknown, our increasing knowledge of the mechanisms underlying pathogenic events in rheumatoid synovitis has enabled selective targeting of the pathogenic elements of disease. Several new drugs have recently been introduced for the treatment of RA. These include cyclooxygenase type 2 inhibitors, adhesion molecules, T cells, B cells, cytokine/receptor, chemokines, angiogenesis, oral tolerance antigens, costimulatory molecules, and new disease-modifying antirheumatic drugs. Continuing research into the pathogenesis of RA will undoubtedly identify even more effective therapeutic approaches for the management of this disease in the future. In conclusion, the proof of principle has been established that selective targeting of pathogenic elements of disease results in substantial improvement in signs and symptoms as well as disease progression. Improved efficacy is expected with more aggressive targeting of the pathogenic elements.
16357711 Erythema elevatum diutinum in the setting of connective tissue disease and chronic bacteri 2005 Apr Erythema elevatum diutinum (EED) is a rare and chronic cutaneous leukocytoclastic vasculitis. It is predominantly seen on the extensor surfaces of the extremities. Although a specific cause is largely unknown, EED has been noted to occur in association with a wide variety of diseases. A 28-year-old man with systemic lupus erythematosus (SLE) and a 53-year-old woman with an overlap syndrome of rheumatoid arthritis and polymyositis are presented. Both patients developed EED in the setting of chronic recurrent bacterial infections. Patients with a connective tissue disease are at increased risk for such infections secondary to immunosuppression, either from the disease itself or secondary to immunosuppressive therapy. EED has been independently reported to occur in the setting of connective tissue disease as well as in the setting of chronic infection. Our patients had both of these underlying conditions, which are known to predispose patients to immune complex-mediated vasculitides, in this case EED. One patient's EED responded to treatment of the SLE and the other improved, as has been previously reported with dapsone.
17212998 Role of abatacept in the management of rheumatoid arthritis. 2006 Nov BACKGROUND: Rheumatoid arthritis (RA) has been associated with significant morbidity and economic burden. Traditional pharmacotherapy (eg, NSAIDs, corticosteroids, disease-modifying antirheumatic drugs [DMARDs]) can be inadequate in controlling symptoms and disease progression. Abatacept is the first selective co-stimulation modulator approved by the US Food and Drug Administration for the management of RA. It is a fusion protein developed to modulate the T-cell co-stimulatory signal that is mediated through the CD28-CD80/86 pathway. OBJECTIVE: The objective of this manuscript was to review the clinical pharmacology, pharmacokinetic and pharmacodynamic properties, tolerability, and clinical efficacy of abatacept. METHODS: MEDLINE and International Pharmaceutical Abstracts were searched through June and May, respectively, of 2006 using the term abatacept or CTLA4-Ig. All prospective, randomized, Phase II and III trials, and their extension phases, were included. RESULTS: Phase II and III clinical trials found that abatacept, at a dose of 10 mg/kg administered as a short i.v. infusion in combination with DMARDs, was associated with significant clinical benefit in patients with active RA. After 6 months of treatment, the American College of Rheumatology (ACR) criteria for 20% clinical improvement (ACR20 response) was attained in 41.9% to 67.9% of patients who received abatacept compared with 19.5% to 39.7% of patients who received placebo (P < 0.001). The percentages of patients achieving the ACR criteria for 50% and 70% clinical improvement (ACR50 and ACR70) were 20.3% to 39.9% and 10.2% to 19.8%, respectively, in the groups that received abatacept compared with 3.8% to 16.8% and 1.5% to 6.5%, respectively, in the patients who received placebo (P = 0.03 and P < 0.001). Additionally, abatacept was found to improve disease activity, physical function, pain, and health-related quality of life (HRQOL). The most commonly reported adverse effects associated with abatacept treatment were headache (18.2%), upper respiratory tract infection (12.7%), nasopharyngitis (11.5%), and nausea (11.5%). The incidences of infections and serious infections were higher in the group that received abatacept compared with patients who received placebo (53.8% vs 48.3% and 3.0% vs 1.9%, respectively; P not reported). No significant between-group differences in mortality were found. CONCLUSIONS: Available evidence suggests that abatacept was effective in controlling symptoms and improving HRQOL in patients with active RA and an inadequate response to DMARD therapy. The most commonly reported adverse effects associated with abatacept treatment were headache, upper respiratory infection, nausea, and nasopharyngitis. Additional trials are needed to determine the long-term safety profile of this agent and whether the clinical benefits of abatacept found in the current clinical trials will be sustained over time.
16277676 Elimination of rheumatoid synovium in situ using a Fas ligand 'gene scalpel'. 2005 Surgical synovectomy to remove the inflammatory synovium can temporarily ameliorate rheumatoid inflammation and delay the progress of joint destruction. An efficient medically induced programmed cell death (apoptosis) in the rheumatoid synovium might play a role similar to synovectomy but without surgical tissue damage. Gene transfer of Fas ligand (FasL) has increased the frequency of apoptotic cells in mouse and rabbit arthritic synovium. In this study, we investigated whether repeated FasL gene transfer could remove human inflammatory synovial tissue in situ and function as a molecular synovectomy. Briefly, specimens of human synovium from joint replacement surgeries and synovectomies of rheumatoid arthritis (RA) patients were grafted subcutaneously into male C.B-17 severe combined immunodeficiency (SCID) mice. Injections of a recombinant FasL adenovirus (Ad-FasL) into the grafted synovial tissue at the dosage of 10(11) particles per mouse were performed every two weeks. Three days after the fifth virus injection, the mice were euthanized by CO2 inhalation and the human synovial tissues were collected, weighed and further examined. Compared to the control adenovirus-LacZ (Ad-LacZ) and phosphate buffered saline (PBS) injected RA synovium, the Ad-FasL injected RA synovium was dramatically reduced in size and weight (P < 0.005). The number of both synoviocytes & mononuclear cells was significantly reduced. Interestingly, an approximate 15-fold increased frequency of apoptotic cells was observed in RA synovium three days after Ad-FasL injection, compared with control tissues. In summary, our in vivo investigation of gene transfer to human synovium in SCID mice suggests that repeated intra-articular gene transfer of an apoptosis inducer, such as FasL, may function as a 'gene scalpel' for molecular synovectomy to arrest inflammatory synovium at an early stage of RA.
16239971 BLyS and APRIL in rheumatoid arthritis. 2005 Nov The cytokines B lymphocyte stimulator (BLyS) and a proliferation-inducing ligand (APRIL) enhance autoimmune disease by sustaining B cell activation. In RA, B cells contribute to the formation of 3 functionally distinct types of lymphoid microarchitectures in the inflamed synovium: ectopic GCs; T cell-B cell aggregates lacking GC reactions; and unorganized, diffuse infiltrates. We examined 72 tissues representing the 3 types of synovitis for BLyS and APRIL production and for expression of APRIL/BLyS receptors. Biologic effects of BLyS and APRIL were explored by treating human synovium-SCID mouse chimeras with the APRIL and BLyS decoy receptor transmembrane activator and CAML interactor:Fc (TACI:Fc). GC+ synovitis had the highest levels of APRIL, produced exclusively by CD83+ DCs. BLyS was present in similar levels in all tissue types and derived exclusively from CD68+ macrophages. In GC+ synovitis, treatment with TACI:Fc resulted in GC destruction and marked inhibition of IFN-gamma and Ig transcription. In contrast, inhibition of APRIL and BLyS in aggregate and diffuse synovitis left Ig levels unaffected and enhanced IFN-gamma production. These differential immunomodulatory effects correlated with the presence of TACI+ T cells in aggregate and diffuse synovitis and their absence in GC+ synovitis. We propose that BLyS and APRIL regulate B cell as well as T cell function and have pro- and antiinflammatory activities in RA.
15801236 [Mechanisms of immunotropic effect of the drug composition Taban-Arshan (Tibet medicine) o 2005 Jan The extract of the Tibetan medicine Taban-Arshan corrects changes of the immune system in inflammatory diseases--rheumatoid arthritis and atopic bronchial asthma. An immunomodulating effect of the drug consists in its ability to suppress hyperactivation of lymphocytes by normalization of expression of basic activation antigens.