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ID PMID Title PublicationDate abstract
16164224 [Anti-AP-1 treatment]. 2005 Sep This review emphasizes our first discovery on the contribution of over-activation of c-fos gene to the pathogenesis of rheumatoid joint destruction. In particular, c-Fos signalling was required for increased activity of synovial mesenchymal cells which finally leads to rheumatoid joint destruction and peri-articular osteoporosis. Over-activation of c-fos via Wee1 kinase is responsible for tumor-like synovial over-growth. Our team designed anti-c-Fos drugs that specifically inhibit action of c-Fos at the AP-1 consensus sequence by using a computer-assisted drug design, which was the front-runner work executed in Japan.
16142749 Fcgamma receptor type IIIA polymorphisms influence treatment outcomes in patients with inf 2005 Sep OBJECTIVE: To determine whether polymorphisms in Fcgamma receptor type IIIA (FcgammaRIIIA) correlate with clinical efficacy in patients with rheumatoid arthritis (RA) and patients with psoriatic arthritis (PsA) being treated with tumor necrosis factor alpha (TNFalpha) inhibitors. METHODS: The study group comprised 30 patients with RA and 5 patients with PsA. Patients were classified as being very good responders (n = 23) or nonresponders (n = 12) to therapy with TNF blocking agents. Whole blood was obtained from all patients, and DNA was extracted for FcgammaRIIIA analysis. The FcgammaRIIIA-158 polymorphism was determined using an allele-specific polymerase chain reaction assay. RESULTS: The distribution of FcgammaRIIIA-158 genotypes was as follows: for F homozygous (F/F), 31.5%; for V homozygous (V/V), 11.5%; and for V/F heterozygous (V/F), 57%. Among very good responders, the distribution of alleles was as follows: for F/F, 48%; for V/V, 13%; and for V/F, 39%. Among nonresponders, the distribution of alleles was as follows: for F/F, 0%; for V/V, 8%; and for V/F, 92%. The low-affinity F/F homozygous genotype was found to be significantly associated with response to TNF inhibitor therapy (P < 0.01 by Fisher's exact test). CONCLUSION: These results suggest that FcgammaRIIIA-158 polymorphisms may affect the outcome of treatment with TNF blocking agents. Better understanding of the factors affecting responses to these agents could result in improved outcomes of treatment.
16397069 Acquired haemophilia heralded by bleeding into the oral mucosa in a patient with bullous p 2006 Jan Acquired haemophilia is rare and potentially fatal, with a mortality of 20% if left untreated. There is a strong association with other autoimmune diseases. This report describes a patient with rheumatoid arthritis, vitiligo, and bullous pemphigoid where the diagnosis of acquired haemophilia was made after an extensive bleed into a bullous lesion in the buccal mucosa. This case highlights some of the potential complications of acquired haemophilia and its treatment.
17092341 Differential effects on BAFF and APRIL levels in rituximab-treated patients with systemic 2006 The objective of this study was to investigate the interaction between levels of BAFF (B-cell activation factor of the tumour necrosis factor [TNF] family) and APRIL (a proliferation-inducing ligand) and B-cell frequencies in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) treated with the B-cell-depleting agent rituximab. Ten patients with SLE were treated with rituximab in combination with cyclophosphamide and corticosteroids. They were followed longitudinally up to 6 months after B-cell repopulation. Nine patients with RA, resistant or intolerant to anti-TNF therapy, treated with rituximab plus methotrexate were investigated up to 6 months after treatment. The B-cell frequency was determined by flow cytometry, and serum levels of BAFF and APRIL were measured by enzyme-linked immunosorbent assays. BAFF levels rose significantly during B-cell depletion in both patient groups, and in patients with SLE the BAFF levels declined close to pre-treatment levels upon B-cell repopulation. Patients with SLE had normal levels of APRIL at baseline, and during depletion there was a significant decrease. In contrast, patients with RA had APRIL levels 10-fold higher than normal, which did not change during depletion. At baseline, correlations between levels of B cells and APRIL, and DAS28 (disease activity score using 28 joint counts) and BAFF were observed in patients with RA. In summary, increased BAFF levels were observed during absence of circulating B cells in our SLE and RA patient cohorts. In spite of the limited number of patients, our data suggest that BAFF and APRIL are differentially regulated in different autoimmune diseases and, in addition, differently affected by rituximab treatment.
17977209 Immunomodulatory effects of blood letting cupping therapy in patients with rheumatoid arth 2005 This study was carried out in order to evaluate the efficiency of blood-letting cupping (BLC) therapy as a complementary therapy in management of rheumatoid arthritis (RA) and to investigate its modulatory effects on natural killer cells (NK) and soluble interleukin-2 receptor (SIL-2R). Two groups of RA patients diagnosed according to American Rheumatology Association were included: Group I included 20 patients who received the conventional medicinal therapy of RA, Group II included 30 patients who received combined conventional and BLC therapy. Ten age and sex matched normal controls were also included, as group III. Visual analogue score (VAS), tender joint count (TJC), swollen joint count (SJC), disease activity scores (DAS), laboratory markers of disease activity [erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Rheumatoid factor (RF)] were evaluated on 3 successive months, NK cell (%) measured by flowcytometry and SIL-2R concentrations measured by ELISA were also assessed. After one month of combined therapy there was significant (P < 0.001) reduction in VAS (5.16 +/- 0.28), TJC (11.62 +/- 1.03), SJC (10.13 +/- 1.02) and DAS (5.35 +/- 0.14). Early and marked reductions in laboratory markers of disease activity (26.90 +/- 3.68) for CRP, (51.46 +/- 6.06) for RF and (40.56 +/-3.36) for ESR were also detected as compared to base line, while the effects of conventional therapy appeared late after 3 months of treatment. Conventional therapy induced significant depression in white blood cell (WBC %) (p < 0.001) whereas combined therapy induced marked (p < 0.001) elevation since the first month (8.44 +/- 1.58) compared to base line (6.94 +/- 1.58). There was a significant (P < 0.05) lowering in NK cell (%) with conventional therapy while combined therapy induced significant (P < 0.001) increase (11.33 +/- 0.4.7) compared to base line level (8.50 +/- 0.46). Additionally, combined therapy resulted in marked reduction (P < 0.001) in SIL-2R conc. after 3 months of treatment (1790 +/- 68.11) compared to base line (2023 +/- 92.95), while insignificant reduction was detected with the conventional therapy. The improvement rate (%) of clinical, laboratory cellular & immunological parameters were significantly higher with combined therapy than with conventional therapy. Moreover, strong positive correlations (p < 0.0001) were detected between SIL-R conc. and clinical parameters VAS (r = 0.890), TJC (r = 0.905), SJC (r = 0.872) and DAS (r = 0.923) and also between SIL-R conc. and ESR (r = 0.973), CRP (r = 0.933), RF (r = 0.941), while a strong negative correlation was found with NK count cell % (r = 0.927). In conclusion, BLC therapy combined with conventional therapy may improve the clinical condition of patients with RA. It has modulatory effects on the innate (NK %) and adaptive cellular (SIL-2R conc.) immune responses that could be used as monitoring tools for disease activity and prognosis.
15614487 [Management of affected flexor tendons in rheumatoid arthritis of the hand]. 2005 Jan The affection to the flexor tendons of the patient with rheumatoid arthritis represents a substantial rheumatic change in the hand, which is characterized by restriction of movement, ulnar deviation in the level of the metacarpophalangeal joint and palmar incomplete dislocation. Early treatment by removing any possible constriction areas in synovial proliferations in the area of the flexor pullies or a complete tendosynovectomy makes an extensive restitution possible. In the case of only one ruptured flexor tendon, it can be treated by the transfer of the neighboring superficialis tendon or a tendon transplant. If there are multiple ruptures, the results will be clearly worse in regard to movement and strength, whereby as a rule the result is seriously influenced by articular destruction. Therefore, an early tendosynovectomy and a preventive operation to the wrist have to be recommended.
16652439 Crossroads of B cell activation in autoimmunity: rationale of targeting B cells. 2006 May B cells have historically been considered as not preferentially involved in the immunopathogenesis of inflammatory joint diseases, in particular rheumatoid arthritis (RA), despite the notion that autoantibodies and immune complexes were involved in pathogenesis and served as diagnostic and classification markers. Following initial reports that patients with non-Hodgkin's lymphoma (NHL) and coexisting RA showed improvement in signs and symptoms of RA after anti-CD20 therapy, the role of B cells in autoimmune diseases was reexamined. Potential mechanisms can be inferred from what is known about the role of B cell functions, in particular antigen-experienced memory B cells. Activation of these cells can be dependent on T lymphocytes or independent of them. Once activated, the cells can efficiently act as antigen-presenting cells, can produce inflammatory cytokines, and may alternatively differentiate into antibody-producing plasma cells. These processes contribute to the activation of other immune cells and ultimately to joint destruction in RA. The development and maintenance of RA may be related to both direct and indirect involvement of these B cell-dependent processes. In systemic lupus erythematosus (SLE), the central pathogenic importance of autoimmune B cells is well recognized, based on early recognition of numerous autoantibodies and clinically important immune complexes. Based on the evidence supporting B cell involvement in the pathophysiology of autoimmune diseases, investigations are evaluating the clinical impact of B cell targeted therapies. B cell targeted therapies in human trials include an anti-B lymphocyte stimulator protein agent, belimumab; an anti-CD20 agent, rituximab; and an anti-CD22 antibody, epratuzumab.
16947783 Relationship between genetic variants in the adenosine pathway and outcome of methotrexate 2006 Sep OBJECTIVE: Among patients with rheumatoid arthritis (RA), there is a high degree of interindividual variability in the degree of response to methotrexate (MTX) treatment. This study was undertaken to explore polymorphisms in genes contributing to antiinflammatory adenosine release as novel predictors of MTX treatment outcome. METHODS: In 205 patients with newly diagnosed RA, 5 polymorphisms in 5 genes coding for enzymes related to the release of adenosine were analyzed. All patients received standardized MTX treatment (up to 25 mg per week orally), combined with folic acid. MTX efficacy was evaluated by the Disease Activity Score (DAS) and compared among genotypes. The association between MTX-related adverse events and genotype was also assessed. The following polymorphisms were determined: AMPD1 34C>T, ATIC 347C>G, ITPA 94C>A, MTR 2756A>G, and MTRR 66A>G. When significant differences were found by chi-square analysis, odds ratios (ORs) and 95% confidence intervals were calculated. RESULTS: Patients carrying the AMPD1 34T allele, ATIC 347CC, or ITPA 94CC were more likely to have a good clinical response, as defined by a DAS of < or =2.4 (OR [95% confidence interval] 2.1 [1.0-4.5], 2.5 [1.3-4.7], and 2.7 [1.1-8.1], respectively). The likelihood of a good clinical response was increased if patients possessed all 3 favorable genotypes (OR 27.8 [95% confidence interval 3.2-250]). Regarding toxicity, only ATIC G allele carriers experienced a greater frequency of adverse events (OR 2.0 [95% confidence interval 1.1-3.7]). CONCLUSION: Polymorphisms in the AMPD1, ATIC, and ITPA genes are associated with good clinical response to MTX treatment. These findings indicate that genotyping may help in the identification of patients who will benefit most from MTX treatment and may assist clinicians in making treatment decisions regarding patients with recent-onset RA.
16956432 Recommendations for the use of biologic (TNF-alpha blocking) agents in the treatment of rh 2006 Jul The present report is devoted to drawing up and disseminating specific recommendations for the use of anti-TNF-alpha therapies in patients with rheumatoid arthritis (RA) in Italy. The document reports and discusses the published literature concerning the criteria for inclusion, assessment of response and for withdrawal of treatment with TNF blocking agents in RA. Several specific points concerning more sensitive warnings are discussed: tuberculosis, hepatitis, lymphoma, and cardiovascular risk and induction of autoimmunity. The recommendations are summarized in an 8-point table approved by the executive committee of the Italian Society for Rheumatology.
16374248 Reversible visual loss in a patient with rheumatoid arthritis and the role of vascular ima 2006 Feb Spontaneous vertebral artery dissection is a condition that can have lethal consequences. The condition should be considered in young male patients who present with a stroke. At presentation, headaches, cerebral ischaemic episodes and oculosympathetic paresis are the most commonly encountered manifestations. The diagnosis is confirmed with angiography. Here, we present a middle-aged male gardener with rheumatoid arthritis and signs of vertebral artery dissection to highlight the importance of diagnosis and discuss the controversies in management.
16899107 Interleukin-6 and chronic inflammation. 2006 Interleukin (IL)-6 is produced at the site of inflammation and plays a key role in the acute phase response as defined by a variety of clinical and biological features such as the production of acute phase proteins. IL-6 in combination with its soluble receptor sIL-6Ralpha, dictates the transition from acute to chonic inflammation by changing the nature of leucocyte infiltrate (from polymorphonuclear neutrophils to monocyte/macrophages). In addition, IL-6 exerts stimulatory effects on T- and B-cells, thus favoring chronic inflammatory responses. Strategies targeting IL-6 and IL-6 signaling led to effective prevention and treatment of models of rheumatoid arthritis and other chronic inflammatory diseases.
16674119 Nanobacteria-like particles in human arthritic synovial fluids. 2006 May We investigated the existence of nanosize particles in synovial fluids of rheumatoid arthritis and osteoarthritis patients. These specimens were cultured under mammalian cell culture conditions (37 degrees C; 5% CO2/95% air) for a long period. After about 2 months, many nanoparticles appeared and they gradually increased in number and in size. The nanobacteria-like particles exist in synovial fluids of arthritis patients. The possibility of their existence and pathogenesis in various diseases should be verified cautiously.
15846591 Radiation exposure in rheumatology practice. 2005 Apr BACKGROUND: Patients encountered in rheumatology practice often have concerns about radiation exposure from the imaging procedures used to diagnose and monitor their diseases. However, such imaging procedures normally deliver radiation doses that are associated with only a low level of risk. OBJECTIVES: To review and quantify the radiation doses delivered by the various imaging procedures commonly ordered in a rheumatology practice and to compare those doses with background radiation exposure in the United States. METHODS: The authors reviewed and compiled literature on radiation exposure from background radiation and diagnostic imaging procedures. The review included a Medline search through December 2003. RESULTS: Radiation doses from medical imaging procedures are so low that they do not have a clinically significant effect on mortality rates. In comparison to our normal daily exposures from naturally occurring background radiation and daily activities, the exposures from medical procedures are quite small. Moreover, the International Commission for Radiological Protection (ICRP) recommends that dose limits should not be applied to medical exposures in nonpregnant patients. Rather, the ICRP recommends that the medical exposure be justified and the protection be optimized so that the dose to the patient is as low as is compatible with the medical purpose. CONCLUSIONS AND RELEVANCE: Appropriate care of patients within the rheumatology practice frequently necessitates the use of imaging procedures that utilize ionizing radiation, such as radiographs, computed tomography scans, and bone densitometry. If ordered prudently, the benefits of these imaging procedures supersede the risks imposed by their radiation exposures.
15958762 Emotion regulation predicts change of perceived health in patients with rheumatoid arthrit 2005 Jul OBJECTIVES: To examine whether emotion regulation predicts change of perceived health in patients with rheumatoid arthritis (RA). METHODS: Sixty six patients (44 female, 22 male; mean (SD) age 57.7 (11.6) years) participated in a prospective study. Hierarchical regression analysis was used to predict change of perceived health between study entry and follow up (1(1/2) years later) from the emotion regulation styles ambiguity, control, orientation, and expression at study entry. RESULTS: Valuing and intensely experiencing emotions (emotional orientation) predicted a decrease of positive affect. Difficulty recognising and expressing emotions (ambiguity) predicted an increase of perceived disease activity. Emotion regulation showed no associations with change of negative affect and social and physical functioning. CONCLUSIONS: Two styles of emotion regulation were shown to have a significant though modest role in the prediction of perceived health change in patients with RA. This suggests that the monitoring of emotion regulation may help to identify patients who are at risk for a reduction of perceived health. If our findings were confirmed by experimental research, improving emotion regulation skills might favourably affect perceived health.
16886578 [Genetics in rheumatoid arthritis (RA)]. 2006 Apr Rheumatoid arthritis (RA) is a chronic autoimmune disease. Genetic and environmental factors are implicated in the pathogenesis of RA. In this study we describe numerous genetic phenomena that may be implicated in the etiopathogenesis of RA i.e. antigens of major histocompatibility complex, genetic linkage analysis results of whole genome scan and polymorphism of several genes coding receptors, adhesion molecules and cytokines. Genetic background plays an important role in this disorder and is connected with multiple genes.
16678011 Thioredoxin protects against joint destruction in a murine arthritis model. 2006 May 15 Thioredoxin (TRX) is an oxidative stress-inducible biological antioxidant that is highly expressed in the synoviocytes of rheumatoid arthritis (RA) patients. There is much evidence that oxidative stress plays a key role in the inflammation and destruction of RA joints; the functional relationship between TRX and RA remains unknown, however. We therefore investigated the role played by TRX in the inflammatory and joint-damaging processes of RA using a murine model in which arthritis was induced by administering a mixture of anti-type II collagen monoclonal antibodies (mAb) and lipopolysaccharide (LPS). In Wt mice mAb/LPS injection induced neutrophil infiltration, cartilage destruction, and chondrocyte apoptosis within the joints, all of which were dramatically suppressed in TRX transgenic (TRX-Tg) mice. Moreover, the 8-hydoxy-2'-deoxyguanosine (8-OHdG) expression seen in Wt mice after mAb/LPS injection was almost completely inhibited in TRX-Tg mice. The administration of recombinant TRX also suppressed mAb/LPS-induced joint swelling in Wt mice. Taken together, these results suggest that TRX protects against arthritis and is a plausible candidate with which to develop novel therapies for the treatment of RA.
14673618 Radon therapy for the treatment of rheumatic diseases--review and meta-analysis of control 2005 Apr OBJECTIVE: The aim of this study was to analyze the effect of radon therapy on pain in rheumatic diseases. METHODS: MEDLINE and MedKur databases were searched for the terms radon plus therapy, rheum, arthritis, and osteo. Radon therapy centers and experts in the field were contacted, proceedings hand-searched, and bibliographies checked for references of potential importance. Included were all prospective randomized controlled clinical trials that compared clinical effects of radon therapy with other interventions in patients with rheumatic diseases and studied pain intensity. Information concerning patients, interventions, results, and methodology were extracted in a standardized manner by all authors independently and summarized descriptively. Reports on pain reduction were pooled for meta-analysis. RESULTS: Five clinical trials with a total of 338 patients and comparing the effect on pain of radon baths (three trials) or radon speleotherapy (two trials) with control intervention in degenerative spinal disease (two trials), rheumatoid arthritis (one trial) and ankylosing spondylitis (two trials) met the inclusion criteria. In meta-analysis, the pooled data showed no difference immediately after treatment (P=0.13) but significantly better pain reduction in the radon group than the control group at 3 months (P=0.02) and 6 months (P=0.002) after treatment. CONCLUSIONS: The existing trials suggest a positive effect of radon therapy on pain in rheumatic diseases. With respect to the potential clinical effect and given the increasing public interest in radon therapy, there is an urgent need for further randomized controlled clinical investigations with long-term follow-up.
17136355 Determination of ANA specificity using multiplexed fluorescent microsphere immunoassay in 2007 May To evaluate ANA specificity using the fully automated multiplexed fluorescent microsphere immunoassay in patients affected either by rheumatoid arthritis or ankylosing spondylitis who developed strong positivity for ANA as assessed by indirect immunofluorescent method on HEp-2 cells during infliximab treatment. Three men affected by ankylosing spondylitis and 12 women affected by rheumatoid arthritis who developed ANA positivity at high titres during infliximab treatment underwent the identification of ANA specificity by multiplexed fluorescent microsphere immunoassay; moreover anti-DNA and anti-ENA antibodies were tested by indirect immunofluorescence and ELISA method, respectively. In 4 out of 15 cases, the determination of ANA reactivity by multiplexed fluorescent microsphere immunoassay was also performed on the serum collected before infliximab administration. One patient affected by rheumatoid arthritis showed multiple ANA reactivities against SS-A, SS-B, RNP, Sm, Jo-1 and histones; one patient affected by ankylosing spondylitis resulted positive for the same autoantibodies, except for anti-Sm antibody. Moreover, two patients, one with rheumatoid arthritis and one with ankylosing spondylitis, showed single antibody specificity to SS-B and RNP, respectively. The remaining 11 cases did not show any positivity. Instead, all the patients resulted negative for anti-ENA antibodies by the ELISA method. In the four cases tested for ANA specificity by multiplexed fluorescent microsphere immunoassay before and after infliximab administration no difference was found. The search for anti-DNA antibody always resulted negative by both the traditional immunofluorescent assay and the novel technique. The use of multiplexed fluorescent microsphere immunoassay in patients treated with infliximab with ANA positivity at high titres allowed to find some ANA specificities which were not revealed by ELISA method. Nevertheless, the majority of patients resulted negative in spite of ANA positivity at high titres; the molecular target of ANA which develop after infliximab administration still remains to be identified.
16441480 HLA class II disease associations in southern Africa. 2006 Feb Southern Africa harbors several population groups representing a diversity of gene pool origins. This provides a unique opportunity to study genetic disease predisposition in these populations against a common environmental background. Human leukocyte antigen (HLA) association studies of these populations could improve knowledge on inter-population variation and HLA-related disease susceptibility. The aim of this paper is to review HLA class II disease associations reported for southern African population groups, compare them with findings in other populations and identify those unique to southern Africa. A number of HLA class II disease associations appear to be unique to southern African populations. These include DRB1*14011 association with insulin-dependent diabetes mellitus susceptibility in the Xhosa and DRB1*10 and DQB1*0302 with rheumatoid arthritis susceptibility in the South African (SA) Indian and SA Coloreds, respectively. A noteworthy similarity in class II disease association was observed among southern African Caucasoid and their European parental populations. Unique HLA class II disease associations observed in southern Africa are consistent with the notion that unique environmental and natural selective factors have resulted in certain ethnic-specific HLA class II disease associations, while common HLA class II disease associations found across different populations support the notion that common diseases are caused by common, ancient alleles present in indigenous African populations.
17023258 Power Doppler ultrasound in musculoskeletal disease: a systematic review. 2006 Oct OBJECTIVE: To evaluate the performance characteristics of power Doppler ultrasound as a diagnostic and monitoring tool in the assessment of musculoskeletal disease through a systematic review of the literature. SEARCH STRATEGY: We performed a literature search of PUBMED (1966 to June 2005). SELECTION CRITERIA: Only original research reports written in English involving musculoskeletal disease and power Doppler ultrasound were included. Reviews were noted but not included. Data Extraction/Reporting: The design, subjects, methods, imaging protocols, and performance characteristics studied in the research papers were reported. RESULTS: Of 3568 identified reports, 139 involved power Doppler ultrasound of the musculoskeletal system. Fifty-three of these reports met the inclusion criteria. Ultrasound machine settings were specified in 63% of reports. Rheumatoid arthritis was the most commonly studied musculoskeletal disease (64% of papers). Validity was the most studied performance characteristic (94% of reports), while reliability and responsiveness were studied in 17 and 34%, respectively. CONCLUSIONS: Although the majority of research reports of power Doppler ultrasound assessment of the musculoskeletal system evaluated validity, less than half reported reliability and responsiveness. Further work is needed to evaluate power Doppler ultrasound assessment of the musculoskeletal system before it can be used to guide clinical decisions or be used as an endpoint in clinical trials.