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ID PMID Title PublicationDate abstract
16783460 Antigen-specific expansion of TCR Vbeta3+ CD4+ T cells in the early stage of collagen-indu 2006 May To investigate type II collagen (CII)-specific CD4+ T cell receptors involving in Collagen-induced arthritis (CIA) in DBA/1J mice as a model of rheumatoid arthritis in humans, TCR Vbeta usage in draining lymph nodes (dLNs) was assessed by flow cytometric analysis at 3, 5, and 8 weeks after bovine CII immunizations. In the early stage of CIA, the draining lymph node CD4+ T cells from CIA mice showed a higher proportion of CD4+ Vbeta3+ subsets compared with those from control mice. The CD4+ Vbeta3+ T cells were specifically and primarily expanded by antigen-specific stimulation in in vitro culture of dLNs lymphocytes and splenocytes from CIA mice. In addition, CII-reactive response was observed when CD4+ Vbeta3+ T cells were added to a non-responding T cell population. The adoptive transfer of CD4+ Vbeta3+ T cells produced exaggerated arthritis compared with that in the control group. Our results indicate that CD4+ Vbeta3+ T cells, which were selectively expanded in dLN of CIA mice, play a pivotal role in CIA pathogenesis.
17992594 Lessons from diseases mimicking Sjögren's syndrome. 2007 Jun Sjögren's syndrome (SS) is a systemic autoimmune disease that mainly affects the exocrine glands and usually presents as persistent dryness of the mouth and eyes because of functional impairment of the salivary and lacrimal glands. The histological hallmark is a focal lymphocytic infiltration of the exocrine glands, and the spectrum of the disease extends from an organ-specific autoimmune disease (autoimmune exocrinopathy) to a systemic process with diverse extraglandular manifestations. In the absence of an associated systemic autoimmune disease, patients with this condition are classified as having primary SS. The differential diagnosis includes processes that specifically involve the exocrine glands. On the one hand, some chronic viral infections may induce lymphocytic infiltration of the exocrine glands, in some cases indistinguishable from that observed in primary SS. On the other hand, some processes may mimic the clinical picture of SS through nonlymphocytic infiltration of the exocrine glands. This review focuses on these two groups of diseases that mimic SS (infections and infiltrating processes).
17417997 Fucosylation in synovial fluid as a novel clinical marker for differentiating joint diseas 2007 Jan OBJECTIVE: To investigate fucosylation of synovial fluid glycoproteins in patients with rheumatoid arthritis (RA), juvenile arthritis (JIA), gonarthrosis (GA) and reactive arthritis (ReA), referred to traumatized knee (TK). METHODS: Synovial fluid glycoproteins were separated by SDS-PAGE and either silver stained or blotted onto nitrocellulose and probed with the fucose-specific Aleuria aurantia lectin. Five bands were chosen for densitometric analysis. Total fucose content and density of fucosylated epitopes were analyzed. RESULTS: Fucose content was elevated in all patient groups and almost all bands, comparing to TK. The density of fucosylated epitopes was increased in the 42-kDa band of RA and JIA cases, and lowered in the 26-kDa band of RA and JIA, but not in GA. In all RA cases FR 42-kDa > FR 26-kDa. The relation was opposite in 8 out of 9 GA cases. CONCLUSION: The density of fucosylated epitopes differs significantly in particular glycoproteins of synovial fluid in joint diseases and may be of potential diagnostic value in differentiating diseases of inflammatory and degenerative origin.
19213510 [Update in treatment of psoriatic arthritis]. 2008 Dec Psoriatic arthritis is a chronic rheumatic disease making part of spondylarthropathies. It is the most frequent chronic inflammatory rheumatism after rheumatoid arthritis. Eventhough, it is usually a benign affection, it may be destructive leading to handicap. Several new medications have been introduced, including anti-tumor necrosis factor (TNF alpha blockers) and leflunomide for treatment of psoriatic arthritis. Many studies show the efficacy of these medications in this disease.
17879732 [Clinical obervation of Jiedu Tongluo Lishi decoction on treating reactive rheumatoid arth 2007 Jul OBJECTIVE: To explore the clinical curative effect and safety of Jiedu Tongluo Lishi decoction on treating active rheumatoid arthritis (RA). METHOD: 106 cases of RA in active period were randomly divided into the integrated Chinese and western medicine group (n=54) and western medicine contrast group (n=52). The former group were treated by Jiedu Tongluo Lishi decoction combined with SASP, the latter by MTX combined with SASP. The arthritis morning stiffness time, ache indexes, tumidness indexes, function indexes, hands grip, 20-m walking time and experimental indexes including ESR, RF, CRP, C3, immune globin of both groups were observed and compared. RESULT: The obviously clinical effective ratio and the total clinical effective ratio in the former group were 77.78% and 90.74% respectively, which are better than those in the latter group (59.62% and 71.15% respectively) (P < 0.01). The arthritis morning stiffness time, ache indexes, tumidness indexes, function indexes, hands grip and 20-m walking time in both groups were obviously released after treatment (P < 0.01). The clinical release in the former group was better than that in the latter group (P < 0.05). ESR, RF and CRP in both groups were markedly improved (P < 0.05). The improvement of ESR, RF, CRP, C3 and IgA in the former group were better than those in the latter group (P < 0.05). The side effect includes gastroenteric tract reaction, decrease of leucocyte, abnormity of liver function, tetter and catamenia maladjustment. The occurent ratio in the former group was 7.41%, which was obviously lower than that in the latter group (15.38%) (P < 0.01). CONCLUSION: The compositively clinical curative effect of Jiedu Tongluo Lishi decoction combined with MTX on treating RA is obviously better than that of western medicine only such as MTX and SASP, with less side effect and higher safety, which is worth applying in clinics extensively.
17363402 Reduction of arthritis following intra-articular administration of an adeno-associated vir 2007 Sep BACKGROUND: In the context of preclinical development, we studied the potential of intra-articular gene delivery using a recombinant adeno-associated virus 5 (rAAV5) encoding a chimeric human tumour necrosis factoralpha (TNFalpha) soluble receptor I linked to a mouse immunoglobulin heavy chain Fc portion (TNF receptor I; TNFRI-Ig). METHODS: Expression was under control of a nuclear factor kappa B (NFkappaB)-responsive promoter and compared with a cytomegalovirus (CMV) promoter (rAAV5.NFkappaB-TNFRI-Ig and rAAV5.CMV-TNFRI-Ig, respectively). RESULTS: Fibroblast-like synoviocytes transduced in vitro with rAAV5.NFkappaB-TNFRI-Ig were able to produce TNFRI-Ig protein in response to several stimuli, and this was inhibited upon treatment with a specific NFkappaB blocking agent. A bioassay revealed that the synthesised TNFRI-Ig was bioactive, showing a higher affinity for human than for rat TNFalpha. Transcription of the transgene and protein production were detectable in joints injected with both constructs. No dissemination of the vector was observed outside the joints. A significant reduction in paw swelling was seen in rats treated with rAAV5.NFkappaB-TNFRI-Ig. This clinical effect was accompanied by a decrease in pro-inflammatory cytokine levels and an increase in IL10 expression in the synovium. CONCLUSION: These results provide evidence that intra-articular gene therapy using rAAV5 encoding TNFRI-Ig may be a safe and feasible approach for the treatment of rheumatoid arthritis. The higher affinity for human TNFalpha suggests that in patients with rheumatoid arthritis the therapeutic effect might be even more pronounced than in rat adjuvant arthritis.
17268787 [Urgent indications for spinal surgery in patients with rheumatoid inflammation]. 2007 Feb The urgency of spinal procedures for rheumatoid inflammatory disease is presented in three typical spinal involvements. Characteristic connections between rheumatoid arthritis and the cervical spine, spinal fractures in ankylosing spondylitis and the occurrence of bacterial spondylodiscitis as a side effect of immunosuppression are discussed.
17850593 Efficacy of anti-CD20 treatment in patients with rheumatoid arthritis resistant to a combi 2007 Oct Rheumatoid arthritis (RA) is characterized by chronic joint inflammation and destruction. B cells play important role in modulating immune responses in RA. In the present study we assessed the impact of the B cell targeting as a third line treatment option. Forty-six patients with established erosive RA non-responding to combination treatment with DMARDs and TNF-alpha inhibitors were treated with anti-CD20 antibodies (rituximab). Rituximab was given intravenously once weekly on four occasions. All patients continued with the previous DMARD. Patients were followed by DAS28, levels of circulating B cells, frequency of immunoglobulin-producing cells, immunoglobulins, and rheumatoid factor levels during the period of 12-58 months. Clinical improvement was achieved in 34 of 46 patients (73%) supported by a significant reduction in DAS28 (from 6.04 to 4.64, P < 0.001). Infusion of rituximab resulted in the elimination of circulating B cells in all but one patient. Within 12 months follow-up, B cells returned to circulation in 86% of patients. Fifty-three percent of the patients were successfully retreated with rituximab or re-started with anti-TNF-alpha treatment. Of the 11 non-responders, five were retreated with anti-CD20 within 2 months, four of them with success, four patients received TNF-alpha inhibitors, the remaining two patients received an additional DMARD. Most of the RA patients resistant to TNF-alpha inhibitors may be effectively treated with anti-CD20 antibodies. The treatment is well tolerated and may be used repeatedly in the same patient and potentially increase sensitivity to previously inefficient treatment modalities.
17324969 IL1 and TNF gene polymorphisms in patients with juvenile idiopathic arthritis treated with 2007 Jul OBJECTIVE: To investigate the genetic contribution of cytokine gene polymorphisms (interleukin 1 (IL1) and tumour necrosis factor alpha (TNFalpha)) on disease phenotype and on response to TNF-blocking agents in a population of patients with juvenile idiopathic arthritis (JIA). METHODS: A cohort of 107 consecutive patients with JIA who were receiving treatment with anti-TNF agents was enrolled in this study. Analysis of genetic polymorphisms for IL1B +3954, IL1RA +2018, TNFalpha -238 and TNFalpha -308 was performed by enzyme-linked oligo sorbent assay, and compared with those obtained from 630 healthy Caucasians and 263 adult patients with rheumatoid arthritis. Relevant demographic, clinical and laboratory data were collected from clinical charts and entered into a customised database, and chi(2) analysis was performed to compare cytokine polymorphisms with disease type according to the International League of Associations for Rheumatology criteria, presence of uveitis, rheumatoid factor and anti-nuclear antibody positivity, erosive disease, frequency of adverse effects to anti-TNF and clinical response after 3 months. RESULTS: The T/T genotype of the IL1B +3954 polymorphism was absent in patients with JIA and present in 5% of controls (p = 0.015). No significant correlation was found between the studied polymorphisms and clinical or laboratory variables considered. Clinical response to TNF inhibitors at 3 months was not associated with the genetic polymorphisms considered. CONCLUSION: In our cohort, the absence of the rare IL1B +3954 gene polymorphism was associated with JIA, but without specificity to particular disease phenotypes. The TNF and IL1 gene polymorphism studied did not seem to be associated with response to anti-TNF treatment.
16704744 Inhibition of macropinocytosis blocks antigen presentation of type II collagen in vitro an 2006 Professional antigen-presenting cells, such as dendritic cells, macrophages and B cells have been implicated in the pathogenesis of rheumatoid arthritis, constituting a possible target for antigen-specific immunotherapy. We addressed the possibility of blocking antigen presentation of the type II collagen (CII)-derived immunodominant arthritogenic epitope CII259-273 to specific CD4 T cells by inhibition of antigen uptake in HLA-DR1-transgenic mice in vitro and in vivo. Electron microscopy, confocal microscopy, subcellular fractionation and antigen presentation assays were used to establish the mechanisms of uptake, intracellular localization and antigen presentation of CII by dendritic cells and macrophages. We show that CII accumulated in membrane fractions of intermediate density corresponding to late endosomes. Treatment of dendritic cells and macrophages with cytochalasin D or amiloride prevented the intracellular appearance of CII and blocked antigen presentation of CII259-273 to HLA-DR1-restricted T cell hybridomas. The data suggest that CII was taken up by dendritic cells and macrophages predominantly via macropinocytosis. Administration of amiloride in vivo prevented activation of CII-specific polyclonal T cells in the draining popliteal lymph nodes. This study suggests that selective targeting of CII internalization in professional antigen-presenting cells prevents activation of autoimmune T cells, constituting a novel therapeutic strategy for the immunotherapy of rheumatoid arthritis.
18851803 Application of the Endomodel rotating hinge knee prosthesis for knee osteoarthritis. 2008 Fall One hundred thirty-six knees were treated with the Endomodel rotating hinge knee prosthesis as primary total knee arthroplasty (TKA). The indications for surgery included osteoarthritis (110 knees), rheumatoid arthritis (18 knees), and osteonecrosis (8 knees). Patients were divided into four study groups according to follow-up duration. Group A was followed up from 10 to 15 years, group B from 8 to 10 years, group C from 5 to 8 years, and group D from 2 to 5 years. The Hospital for Special Surgery knee score, as well as each parameter individually, showed statistically significant improvement in all groups postoperatively. A total of 88.23% were rated as excellent, 3.67% as good, and 8.08% as fair. The results suggest that the Endomodel rotating hinge prosthesis can be considered a good alternative for primary TKA in cases of serious axial deformity and collateral ligament deficiency and in rheumatoid arthritis patients.
17457024 Atlantoaxial dislocation associated with a mass in the extradural craniovertebral junction 2007 Apr A 61-year-old woman without rheumatoid arthritis (RA) was admitted with atlantoaxial dislocation (AAD) and a retroodontoid mass at the craniovertebral junction manifesting as a 1-year history of numbness and mild weakness of the right upper extremity. Computed tomography and magnetic resonance (MR) imaging showed AAD and a mass at the craniovertebral junction. She had no past history of RA or trauma in the head and neck. She underwent surgery to obtain the histological diagnosis of the mass and to improve AAD-induced instability. The lesion was approached through the right transcondylar fossa approach with C-1 laminectomy. Intraoperative pathological examination showed cicatrizing collagen fibers and no obvious tumor cells. After partial removal of the lesion, the AAD was fixed with the posterior approach. The symptoms subsided soon after surgery and the mass decreased on MR images taken 3 months after surgery. If a pseudotumor is suspected based on the preoperative radiological investigation in a non-RA patient with AAD and the symptoms are not progressive, stabilization can be expected to induce spontaneous regression without urgent direct excision of the mass.
17922913 The impact of infliximab treatment on quality of life in patients with inflammatory rheuma 2007 In this study, we compare the health-related quality of life (HRQoL) of patients with moderate-to-severe rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS), and study the effect of treatment with infliximab on the HRQoL of patients with these diseases. Short Form Health Survey-36 (SF-36) data from the placebo-controlled phases of 4 studies of infliximab in patients with inflammatory rheumatic diseases (n = 1990) were evaluated. Data came from the Anti-TNF Trial in Rheumatoid Arthritis with Concomitant Therapy (ATTRACT) (n = 428), the Safety Trial for Rheumatoid Arthritis with REMICADE Therapy (START) (n = 1083), the Ankylosing Spondylitis Study for the Evaluation of Recombinant Infliximab Therapy (ASSERT) (n = 279), and the Infliximab Multinational Psoriatic Arthritis Clinical Trial II (IMPACT II) (n = 200). SF-36 assessments were made at weeks 0, 10, 30, and 54 in ATTRACT, weeks 0, 6, and 22 in START, weeks 0, 12, and 24 in ASSERT, and weeks 0 and 14 in IMPACT II. All patient populations had significantly impaired physical aspects of HRQoL at baseline relative to the general population of the United States, and the magnitude of impairment was similar across the diseases. Mean baseline physical component summary scores were 29 in the RA cohort, 32 in the PsA cohort, and 29 in the AS cohort. In all 3 diseases, patients who received infliximab showed significant improvement in physical component summary scores compared with those who received placebo. The magnitude of the difference of improvement (effect size, 95%CI) between infliximab and placebo groups was similar in the AS (10.1, 9.2-11.0), PsA (8.6, 7.8-9.4), and RA (10.1, 9.2-11.0) cohorts. Patients with RA and those with PsA treated with infliximab also showed greater improvement in the mental component summary score than those in the placebo group with an effect size of 4.6 (4.2-5.1) in RA and 2.7 (2.4-3.1) in PsA. Patients in large randomized controlled studies of infliximab in RA, PsA, and AS had similar impairment in physical aspects of HRQoL at baseline and showed significantly greater improvement in HRQoL after treatment with infliximab.
21794420 [Treatment of rheumatoid arthritis with anakinra: a systematic review]. 2007 Jul OBJECTIVE: To perform a systematic review for evaluating efficacy and safety of anakinra in the treatment of rheumatoid arthritis (RA). MATERIAL AND METHOD: The MedLine, Embase, and Cochrane Library databases were searched from January 2000 to February 2006 by using a high sensitive search that included every randomised controlled trial (RCTs) or controlled trial (CTs) that evaluated either efficacy or safety of Anakinra for the treatment of RA. RESULTS: The search identified four relevant studies to evaluate efficacy. Patients treated with anakinra achieved significantly better clinical responses than those treated with placebo. Anakinra combined with methotrexate provided significantly greater clinical benefit than methotrexate alone. Combination therapy with etanercept and anakinra provides no added benefit and an increased safety risk compared with etanercept alone. Results from a large, placebo-controlled safety study demonstrate that anakinra is safe and well tolerated. The most common adverse effect was a mild local inflammation over the puncture area. CONCLUSIONS: This review confirmed both the efficacy and the safety of anakinra in the short term for the treatment of RA. Anakinra provides adequate clinical responses without major safety problems. This systematic review does not allow us to conclude on Anakinra responses in the long term.
18616417 Inflammatory lipids as a target for therapy in the rheumatic diseases. 2008 Aug As patients with autoimmune rheumatic diseases live longer due to improved therapies and preventive measures, death and disability from cardiovascular events are increasing. Patients with rheumatoid arthritis and systemic lupus erythematosus have an increased risk of atherosclerosis that persists even after accounting for traditional cardiac risk factors. Recent studies strongly suggest that the mechanism is due in part to increased levels of oxidized lipids (such as oxidized low density lipoprotein and pro-inflammatory high density lipoproteins) which cause the inflammatory cascade that ultimately leads to plaque formation. The objective of this review is to discuss how inflammatory lipids contribute to the increased risk of atherosclerosis in rheumatoid arthritis and systemic lupus erythematosus, as well as to propose that these oxidized lipids are a rational target for therapeutic intervention in autoimmune diseases. Published literature was examined to review treatments for pro-inflammatory lipids in autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus. In conclusion, it is possible that these oxidized lipids may also contribute to increased disease manifestations in rheumatic conditions. Several new and existing therapies, including statins and high density lipoprotein-associated protein peptide mimetics such as D-4F (apoA-1) target these oxidized lipids and may be useful in both preventing atherosclerosis and treating inflammation in patients with rheumatic diseases.
16539828 Tumor necrosis factor alpha promoter polymorphisms in patients with juvenile idiopathic ar 2006 Jan OBJECTIVE: To investigate the potential association of tumor necrosis factor-alpha (TNF) promoter alleles within subtypes of juvenile idiopathic arthritis (JIA) compared to healthy controls in a Caucasian population. METHODS: TNF-alpha promoter polymorphisms at positions -163, -238, -244, -308, -376 were determined in 228 patients with JIA and 196 healthy individuals. Genomic DNA was isolated and a PCR fragment of about 500 base pairs of the TNF gene promoter were amplified by PCR. Detection of polymorphisms was achieved by a single sequencing procedure. RESULTS: The TNF -238A allele was more frequent in the psoriatic arthritis JIA subgroup compared to healthy controls as well as to non-psoriatic JIA patients (p < 0.001, chi-square-test) and was associated with the more frequent occurrence of joint erosion (p < 0.05, chi-square-test). The frequency of the TNF -308A allele was significantly lower in patients with rheumatoid factor negative polyarthritis JIA patients compared to healthy controls, respectively (p < 0.05, chi-square-test). Joint erosions were detectable more often in rheumatoid factor negative polyarthritis JIA patients with the G/A genotype (80%) than in those with the G/G genotype (45%) (p = 0.20). The rare alleles at position -376 or at positions -163 and -244 were found very infrequently. CONCLUSION: TNF promoter polymorphisms may play a role in the pathogenesis of JIA. The TNF-238A allele seems to be associated with juvenile psoriatic arthritis. The TNF-308A allele is less frequently found in rheumatoid factor negative but not in rheumatoid factor positive polyarthritis and may therefore be associated with a more severe disease, while the more common TNF-308G allele may be protective.
18466580 Evidence of linkage to chromosome 1 for early age of onset of rheumatoid arthritis and HLA 2007 Focusing on chromosome 1, a recursive partitioning linkage algorithm (RP) was applied to perform linkage analysis on the rheumatoid arthritis NARAC data, incorporating covariates such as HLA-DRB1 genotype, age at onset, severity, anti-cyclic citrullinated peptide (anti-CCP), and life time smoking. All 617 affected sib pairs from the ascertained families were used, and an RP linkage model was used to identify linkage possibly influenced by covariates. This algorithm includes a likelihood ratio (LR)-based splitting rule, a pruning algorithm to identify optimal tree size, and a bootstrap method for final tree selection.The strength of the linkage signals was evaluated by empirical p-values, obtained by simulating marker data under null hypothesis of no linkage. Two suggestive linkage regions on chromosome 1 were detected by the RP linkage model, with identified associated covariates HLA-DRB1 genotype and age at onset. These results suggest possible gene x gene and gene x environment interactions at chromosome 1 loci and provide directions for further gene mapping.
17414954 Economic issues with new rheumatologic therapeutics. 2007 May PURPOSE OF REVIEW: Pharmacoeconomic evaluations are increasingly important in all aspects of medicine. In rheumatology, such studies have become all the more relevant following the introduction of highly effective biologic agents. Brought to the clinic initially for the treatment of rheumatoid arthritis, biologic agents have found expanded indication in other rheumatic diseases. RECENT FINDINGS: Building upon a long tradition in rheumatology, recent studies have updated and expanded upon the costs of various rheumatic diseases. These studies set the stage for determining the value of newer therapies. As a result of the chronic nature of rheumatic diseases, pharmacoeconomic evaluations must be carried out over sufficiently long time frames. Therefore, methodologic issues continue to be an area of ongoing discussion. Finally, ongoing studies have estimated the cost-effectiveness of novel rheumatologic therapies, in particular the inhibitors of tumor necrosis factor. These studies have shown that in several clinical circumstances, tumor necrosis factor inhibitors can indeed have an incremental cost-efficacy within the range of generally accepted medical interventions. While many of these studies focused on rheumatoid arthritis, there is growing interest in pharmacoeconomic evaluations in other rheumatic diseases. SUMMARY: Pharmacoeconomic evaluations are crucial to the optimal use of new therapies in rheumatology.
18779340 Association of Mycoplasma arthritidis mitogen with lethal toxicity but not with arthritis 2008 Nov Mycoplasma arthritidis induces an acute to chronic arthritis in rodents. Arthritis induced in mice histologically resembles human rheumatoid arthritis and can be associated with lethal toxicity following systemic injection. The M. arthritidis mitogen (MAM) superantigen has long been implicated as having a role in pathogenesis, but its significance with respect to toxicity and arthritogenicity in mycoplasma-induced disease is unclear. To study the pathogenic significance of MAM, M. arthritidis mutants that overproduced or failed to produce MAM were developed. MAM overproduction and knockout mutants were more and less mitogenic, respectively, than the wild-type strain. The degree of mitogenic activity correlated with lethal toxicity in DBA/2J mice. In contrast, histopathological studies detected no correlation between MAM production and the severity of arthritis induced in DBA/2J and CBA/J mice.
17118290 Advances in the management of septic arthritis. 2006 Dec Septic arthritis still continues to be a common and serious problem at major urban medical centers and is one of the most rapidly destructive forms of acute arthritis. The yearly incidence of bacterial arthritis varies from 2 to 10 per 100,000 in the general population to 30 to 70 per 100,000 in patients with rheumatoid arthritis and in patients with joint prostheses. Irreversible loss of joint function may develop in up to 50% of the patients. Despite better antimicrobial agents and improved hospital care, the fatality rate for this medical problem has not changed substantially during the past 30 years. An understanding of the risk factors and the pathogenesis of nongonoccocal bacterial arthritis and other forms of infectious arthritis, primarily in the context of a differential diagnosis and treatment, are important to avoid the delay in making a correct diagnosis and to improve the prognosis.