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ID PMID Title PublicationDate abstract
15239536 Thyroid autoantibodies in autoimmune diseases. 2004 Abnormalities in the thyroid function and thyroid autoantibodies have been frequently described in patients with autoimmune diseases but seldom in antiphospholipid syndrome patients. In order to determine the prevalence of thyroid function and autoimmune abnormalities, we compared serum thyrotropin (TSH, serum free thyroxine (T4) levels, thyroid antithyroglobulin (TgAb) and antithyroperoxidase (TPOAb) levels of 25 patients with systemic sclerosis, 25 patients with rheumatoid arthritis and 13 patients with antiphospholipid syndrome to a control group of 113 healthy individuals. Evaluation included a thorough clinical examination with particular attention to thyroid disease and a serologic immune profile including rheumatoid factor, antinuclear and anticardiolipin antibody measurements. Subclinical hypothyroidism (4.2
15222498 [Acute arthritis]. 2004 Apr 15 In the case of inflammatory disease of the joints, the first diagnostic step is to determine whether the patient has monoarthritis, oligoarthritis or polyarthritis. After excluding a septic or a crystal-related process by joint puncture and synovial fluid analysis, further laboratory investigations including immunological and bacteriological tests can contribute to the diagnosis, and imaging procedures may also be useful. Primary therapy can be provided with NSAIDs or easy-on-the-stomach coxibs. Where indicated, antibiotics or, if warranted by the diagnosis and in the presence of persistent effusion, corticosteroids.
11824972 Altered levels of soluble adhesion molecules in patients with rheumatoid arthritis complic 2002 Jan OBJECTIVE: To assess levels of 2 circulating soluble adhesion molecules, vascular cellular adhesion molecule (sVCAM) and E-selectin, in patients with rheumatoid arthritis (RA) complicated by peripheral neuropathy compared to RA patients with no neurological complications and healthy controls. METHODS: In total, 25 RA patients with peripheral neuropathy (detected by clinical examination and confirmed by electromyography and nerve conduction studies), 40 RA patients without peripheral neuropathy, and 25 controls were studied. Clinical and laboratory assessments of disease activity were carried out and levels of sVCAM-1 and E-selectin were measured by ELISA in each of the 3 groups. RESULTS: Levels of sVCAM-1 and sE-selectin were higher (p < 0.001) in RA patients with peripheral neuropathy than in patients without neuropathy and controls. Levels of sE-selectin and sVCAM-1 correlated positively with disease activity variables. Correlation was independent of age and sex. CONCLUSION: Peripheral neuropathy in patients with RA is associated with increased endothelial cell activation evidenced by elevated serum levels of sVCAM-1 and sE-selectin in this group of patients.
15552522 Benefit/risk of cyclosporine in rheumatoid arthritis. 2004 Sep Combination therapy has emerged as a crucial therapeutic tool to control aggressive rheumatoid arthritis (RA). Cyclosporine (CsA) when combined with methotrexate (MTX) has shown substantial benefit in clinical practice. The primary benefit is its positive effect in the control of joint-bone erosions. The most feared adverse effect is the development of nephrotoxicity, which may be in part hemodynamic and in part structural, i.e. fibrotic. Careful monitoring of concomitant drugs, hypertension and through blood levels should allow the patient to maintain normal renal function. The successful employment of CsA in lupus nephritis clearly supports this statement.
15352425 Health care and burden of illness in systemic lupus erythematosus compared to rheumatoid a 2004 During the past 20 years, outcome studies in the rheumatic diseases have, on the one hand, given increasing evidence of the unfavourable long-term prognosis of rheumatoid arthritis (RA) and on the other hand determined continuous improvement of prognosis in systemic lupus erythematosus (SLE). The aim of the study was to investigate how this translates into the current spectrum of patients with rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) seen by rheumatologists in Germany and to compare aspects of the burden of disease, disease outcomes and treatment between these two important rheumatic diseases using a large clinical database. Current health care was analysed with data from the German rheumatological database of 10 068 patients with RA and 1248 patients with SLE seen by rheumatologists in 2001. In addition, of a total of 3546 patients with SLE and 24 969 patients with RA seen at the German Collaborative Arthritis Centres between 1994 and 2001, 3465 cases of SLE were matched by age, sex, disease duration and referral status with a corresponding RA case. There were considerable differences in treatment of patients before referral to a rheumatologist and in rheumatologic care. In 2001, patients with SLE were treated by their rheumatologists mainly with antimalarials (AM, 37%), azathioprine (29%) and nonselective NSAIDs (16%). Of them, 61% received at least one immunosuppressive drug (including AM) plus glucocorticoids. In RA, methotrexate was the predominant medication (63%), and 56% received at least one immunosuppressive drug plus glucocorticoids. Matched pairs analysis showed that SLE patients with a short disease duration were almost equally burdened by pain, functional limitations and reduced health status as RA patients. After a disease duration of >10 years, however, patients with RA showed poorer outcomes than those with SLE: RA patients reported significantly more often severe pain (30% in RA versus 17% in SLE) and poor global health status (52 versus 38%), and their disease activity as well as severity was rated higher by the rheumatologists. In conclusion, comparing large groups of RA and SLE patients we found a similar burden in early but not in late disease. Taking into account limitations as to the generalizability of the results (recruitment in rheumatologic care, cross-sectional data, underestimation of SLE-specific outcomes), the discrepancy between the high increase in disease-related negative outcomes with longer disease duration in RA but not in SLE indicates a better long-term prognosis in SLE concerning the items observed. The great disparity in treatment intensity between rheumatologists and nonrheumatologists shows that the involvement of a specialist is needed equally in both diseases.
15082490 Autoimmune thyroiditis and anti-thyroid antibodies in primary Sjogren's syndrome: a case-c 2004 May OBJECTIVE: To determine the frequency of antithyroid antibodies and the presence of autoimmune thyroiditis among patients with primary Sjögren's syndrome. DESIGN: A case-control study. METHODS: 53 consecutive patients with primary Sjögren's syndrome, 30 with rheumatoid arthritis, 12 with secondary Sjögren's syndrome associated with rheumatoid arthritis, 17 with autoimmune thyroiditis, and 53 apparently healthy controls were studied for anti-TG and anti-TPO antibodies as well as serum thyroid hormones and TSH levels. RESULTS: The overall frequencies of thyroid antibodies were 6/53 (11%) in primary Sjögren's syndrome, 2/30 (7%) in rheumatoid arthritis, 2/12 (17%) in secondary Sjögren's syndrome, 4/53 (8%) in healthy controls, and 16/17 (94%) in autoimmune thyroiditis. There was no difference in the frequency of the thyroid antibodies among the groups if patients with autoimmune thyroiditis were excluded (p = 0.415 for anti-TPO; p = 0.275 for anti-TG; p = 0.696 for either anti-TG and/or anti-TPO). Only two patients with primary Sjogren's syndrome had clinical hypothyroidism associated with autoimmune thyroiditis. CONCLUSIONS: In this Turkish population, no association between primary Sjögren's syndrome and autoimmune thyroiditis was found.
12196041 Anakinra. 2002 Anakinra, a recombinant human interleukin-1 (IL-1) receptor antagonist, is the first biological agent approved to block the pro-inflammatory effects of IL-1 in patients with rheumatoid arthritis. In a double-blind, randomised trial in 472 patients with active, severe or very severe rheumatoid arthritis, recipients of subcutaneous anakinra 150 mg/day achieved higher response rates [assessed using the American College of Rheumatology (ACR) composite score] and accumulated more mean productivity days after 6 months than placebo recipients. However, the response rates and accumulated productivity days of patients receiving subcutaneous anakinra 30 or 75 mg/day for 6 months were similar to those of placebo. With respect to the total Genant radiographic scores, the same study showed that all anakinra treatment regimens slowed disease progression after 6 months to a greater extent than placebo. In double-blind, randomised trials in patients with rheumatoid arthritis, combined treatment with anakinra and methotrexate was associated with higher ACR 20, 50 and 70 response rates than with methotrexate alone. Anakinra, used alone or in combination with methotrexate, was generally well tolerated, with the most frequent adverse event being a mild injection-site reaction of transient duration. Infections requiring antibacterial therapy or hospitalisation occurred more commonly in anakinra recipients than in placebo recipients, but were a rare cause for discontinuation of anakinra therapy (approximately 1%) in clinical trials.
14991180 [Radio-ulnar and radio-scaphoid-lunate arthrodesis in chronic polyarthritis. Clinical and 2004 Feb INTRODUCTION: In 75% of all cases of rheumatoid arthritis the wrist is affected and in 12% is the region of initial manifestation of this chronic inflammatory joint disease. To prevent destruction of the wrist through carpal dislocation, radiolunate and radioscapholunate arthrodeses have increased in importance. METHODS: During a 6.5-year period, 28 radiolunate and 4 radioscapholunate arthrodeses were performed in 30 patients. The indication for operation was progressive carpal translation and increasing subluxation of the wrist in which existent radiological damage had not reached more than grade III according to the classification of Larsen and co-workers. RESULTS: The results obtained during the follow-up study (median: 17.3 months) showed in most treated patients after partial arthrodesis of the wrist no or fewer complaints concerning swelling and pain and an acceptable remaining range of motion of the wrist in everyday life. In patients with preoperatively existing ulnar deviation less than 15 degrees progressive carpal collapse and dislocation could be mostly prevented. CONCLUSION: All told radiolunate and radioscapholunate arthrodeses successfully stabilized the wrist in patients suffering from rheumatoid arthritis.
14652678 Heat shock proteins (HSP) for immunotherapy of rheumatoid arthritis (RA). 2003 Nov Rheumatoid arthritis (RA) is an inflammatory disease that primarily involves the joints and has a worldwide prevalence of about one percent, with a female to male ratio of 3:1. This chapter summarizes some of the recent progress in molecular immunology, and discusses the application of this new knowledge for therapeutic purposes. We focus on our recent experiences and that of others in modulation of antigen specific responses as a tool for manipulating autoimmune inflammation. Particular emphasis is given to the concept of exploiting for therapeutic purposes a natural mechanism of immune regulation. This mechanism is based on sequential cross recognition of bacterial and human derived heat shock protein peptides.
14988353 Best evidence topic report. Intra-articular corticosteroid injections in acute rheumatoid 2004 Mar A short cut review was carried out to establish whether intra-articular corticosteroid injections were effective at reducing pain in patients with acute rheumatoid monoarthritis. Altogether 215 papers were found using the reported search, of which one presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results, and study weaknesses of this best paper are tabulated. A clinical bottom line is stated.
12721694 Rapid sequence quadruple joint replacement in a rheumatoid Jehovah's Witness. 2003 Apr We report the case of a wheelchair-bound rheumatoid Jehovah's Witness who underwent rapid sequence, staged, simultaneous ipsilateral hip and knee replacements. Using perioperative erythropoietin and postoperative blood salvage, all four joints were reconstructed without homologous blood transfusion. One year following surgery, the patient has achieved an independent functional status, and all four replaced joints remain painless.
15183159 Evaluating the validity of animal models for research into therapies for immune-based diso 2004 Jun 15 The last few decades of the 20th century have shown an intensified search for safer and more effective medications against chronic diseases that burden ageing societies of the western world. The impressive development of biotechnological production techniques has greatly facilitated the pharmaceutical development of relatively non-toxic biological molecules. However, despite the huge investments, only a few effective therapies for immune-based diseases have reached the clinic. In this article we use examples from monoclonal antibody trials to discuss the validity and predictive strength of the animal models currently used for the development of effective therapies.
15024135 Development, validation and use of a patient knowledge questionnaire (PKQ) for patients wi 2004 Apr OBJECTIVES: To design and validate a patient knowledge questionnaire (PKQ) to use pre- and post-education programme for a group of early rheumatoid arthritis (RA) patients. The aim was to design a tool to assess knowledge acquisition before and after an arthritis information course (AIC). METHODS: The PKQ design incorporated 12 multichoice questions. Validation procedures were undertaken. Following PKQ validation 30 patients were recruited from specialist practice having met the inclusion criteria. All patients attended the arthritis information course run by the multidisciplinary team. Demographic data such as age, gender, disease duration and educational level were evaluated for possible significance. RESULTS: The PKQ demonstrated test-retest stability with a Pearson's correlation coefficient of 0.965 and an intraclass single measure coefficient of 0.87. Internal consistency was demonstrated with a Cronbach's alpha of 0.62. The PKQ was sensitive to change with a statistically significant improvement following three 1-h education sessions (Mann-Whitney U-test P<0.001). No correlation was found between baseline PKQ scores and age or disease duration. However, significant correlation between educational level and pre-knowledge scores (Pearson's correlation r = 0.386, P = 0.035) was demonstrated. Change in PKQ score was not associated with age, disease duration or educational level. Patients with lower initial pre-scores obtained the most improvement post-AIC (chi(2)-test P = 0.003). CONCLUSIONS: The PKQ is a reliable, valid and sensitive instrument suitable for measuring the acquisition of RA knowledge in a group of early RA patients following arthritis information courses.
12419287 Functional analysis of discoidin domain receptor 2 in synovial fibroblasts in rheumatoid a 2002 Nov In order to know whether any protein tyrosine kinase (PTK) is involved in the over-proliferation and erosiveness of synovial fibroblasts (SF) of rheumatoid arthritis (RA) patients, RT-PCR and RNA dot blotting were done to analyse PTKs profile in RA SF. Platelet-derived growth factor receptor A (PDGFRA), insulin-like growth factor 1 receptor (IGF-1R), Janus kinase 1 (JAK1), TYK2, discoidin domain receptor 2 (DDR2), and Lyn were expressed in SF, and the expression of PDGFRA, IGF-1R, and DDR2 in SF of RA were higher than that of osteoarthritis (OA, as control). Immunoblotting and gelatinase zymography showed that DDR2 in RA SF, which still secreted active matrix metalloproteinase 1 (MMP-1) in vitro, were in active form. Stimulation of collagen II could make NIH-3T3 cells (as control) produce MMP-1, which could be inhibited by soluble extracellular part of DDR2. These results indicated that the over-expression of MMP-1 in RA SF might be related to the activation of DDR2, and collagen II, act as DDR2 ligand, might be one of the stimulators of the over-expression of MMP-1 of RA SF.
12124858 Stromelysin 1 (matrix metalloproteinase 3) and HLA-DRB1 gene polymorphisms: Association wi 2002 Jul OBJECTIVE: To test the hypothesis of an association between a polymorphism in the matrix metalloproteinase 3 (MMP-3) gene promoter and the susceptibility, severity, and progression of rheumatoid arthritis (RA), and to further document the association between HLA-DRB1 alleles encoding the shared epitope (SE) and the severity and progression of RA. METHODS: Patients with early RA (n = 103) were included in this prospective study. A total radiographic damage score (TDS; by the Sharp/van der Heijde method) was used to quantify RA severity at baseline and after 4 years of followup. The 5A/6A biallelic polymorphism in the MMP-3 gene promoter was analyzed using fluorescence-based polymerase chain reaction (PCR). HLA-DRB1 genotyping was performed using PCR methods. Control subjects (n = 127) were unrelated healthy individuals. RESULTS: MMP-3 allele carriage rates and allele and genotype frequencies did not differ between patients and controls. The MMP-3 6A/6A genotype was associated with the highest TDS both at baseline and after a 4-year followup and with the highest progression of the TDS over the 4 years of followup. The DRB1 SE+/+ genotype was associated with the highest TDS after a 4-year followup and with the highest progression of the TDS over the 4 years of followup. Patients homozygous for MMP-3 6A and DRB1 SE had the highest progression of the TDS. CONCLUSION: This study provides the first evidence of an association between a polymorphism in the MMP-3 gene promoter and the severity and progression of RA, but not RA susceptibility. Investigation of this polymorphism could be combined with that of DRB1 gene polymorphism to improve the predictive accuracy and management strategy in early RA.
11840440 Involvement of CD4+,CD57+ T cells in the disease activity of rheumatoid arthritis. 2002 Feb OBJECTIVE: To evaluate the relationship between the frequency of peripheral CD57+ T cells and the physical status of rheumatoid arthritis (RA) patients, and to perform cytokine analysis of these CD57+ T cells. METHODS: Four-color fluorescence-activated cell sorter analysis was performed to detect both cell surface antigens and intracellular cytokines in peripheral blood leukocytes, using monoclonal antibodies against CD3, CD4, CD8, CD57, interferon-gamma (IFNgamma), and interleukin-4 (IL-4). RA patients were clinically evaluated with a modified Health Assessment Questionnaire (M-HAQ), joint score, face scale, and visual analog scale (VAS) assessing pain and disease activity. RESULTS: There was a significant correlation between the frequency of CD4+,CD57+ T cells and erythrocyte sedimentation rate (ESR), whereas a correlation was not found between the frequency of CD8+,CD57+ T cells and ESR. The frequency of CD4+,CD57+ T cells also showed a significant correlation with the mHAQ score, VAS, and face scale. Again, there was no significant correlation between the above-mentioned clinical scores and the frequency of CD8+,CD57+ T cells. Flow cytometric analysis of intracellular cytokines revealed that 14.5% of the CD57+ T cells produced IFNgamma, whereas only 2.8% of the CD57+ T cells produced IL-4 in RA patients. CONCLUSION: Evidence showing that the frequency of CD4+,CD57+ T cells among CD3+ cells of RA patients had a significant correlation not only with ESR but also with the physical status of the patients, and that a large proportion of the CD4+,CD57+ T cells had the capacity to produce IFNgamma, strongly suggests that these CD4+,CD57+ T cells are involved in the immunopathogenesis of RA.
12860724 TNF receptor gene therapy results in suppression of IgG2a anticollagen antibody in collage 2003 Aug BACKGROUND: Therapeutic strategies to block tumour necrosis factor alpha (TNFalpha) activity in experimental autoimmune arthritis models and rheumatoid arthritis (RA) have proved highly successful, and provide sustained beneficial effects. OBJECTIVE: To examine whether TNFalpha inhibition has immunological activity beyond the reduction of inflammation in collagen induced arthritis (CIA), an established experimental model of RA. METHODS: Arthritic DBA/1 mice received single periarticular injections of retroviral constructs encoding human TNF receptor (TNF-R) into the affected arthritic paw, at the onset of arthritis. Severity of arthritis, antibodies to collagen type II (CII), and extent of pathological joint damage of arthritic paws were compared between TNF-R and media treated (control) animals 3, 7, 14, 21, and 49 days after disease onset. RESULTS: Severity of CIA was significantly decreased in TNF-R treated animals compared with controls, 14-34 days after disease onset. Joint destruction was reduced in TNF-R injected joints and in the uninjected contralateral and ipsilateral paws of TNF-R treated animals. Seven days after disease onset, TNF-R treated mice had lower levels of inflammatory Th1 driven IgG2a antibodies to CII (p<0.05) than controls. This altered the anticollagen IgG2a:IgG1 ratio towards Th2 driven IgG1. CONCLUSIONS: Local TNF-R gene therapy in CIA appears to have systemic effects on the anti-CII antibodies. The overall influence of TNF-R gene therapy is that it inhibits the progression of CIA mainly by suppressing the inflammatory Th1 response rather than by stimulating a Th2 response. Therefore, periarticular TNF-R gene therapy may have excellent therapeutic potential in RA.
15529391 Cardiovascular risk factors in women with and without rheumatoid arthritis. 2004 Nov OBJECTIVE: The risk of cardiovascular disease (CVD) is increased in patients with rheumatoid arthritis (RA). The objective of this study was to examine the distribution of known CVD risk factors and biomarkers of CVD in women with and without RA. METHODS: This study included two components: an examination of clinical CVD risk factors among women participating in the Nurses' Health Study, a prospective longitudinal cohort, and an analysis of CVD biomarkers among a subgroup of women from this cohort who provided a blood specimen in 1989 (biospecimen cohort). Data regarding clinical risk factors for CVD were collected in 1990 by mailed questionnaire. The diagnosis of RA was confirmed through a structured medical record abstraction. We compared clinical risk factors for CVD and biomarkers of CVD between women with and without RA, adjusting for age, body mass index (BMI), smoking status, and menopause status. RESULTS: Women with RA (n = 287) were significantly more likely than women without RA (n = 87,019) to report no alcohol use (48.2% versus 39.4%) and past cigarette smoking (47.8% versus 38.0%). No significant differences between these groups were observed for current smoker status, BMI, regular aspirin use, diabetes, hypertension, physical activity, and family history of early myocardial infarction. In the biospecimen cohort (69 RA cases and 491 controls), the levels of several inflammatory biomarkers linked to CVD were significantly elevated in women with RA, including CRP, fibrinogen, sICAM-1, sTNFRI, sTNFRII, and osteoprotegerin. Levels of total cholesterol, low-density lipoprotein, triglycerides, apolipoprotein B, and Lp(a) were similar between groups. Levels of homocysteine were similar, but vitamin B(12) was significantly higher among women with RA than among the controls. CONCLUSION: In women participating in the Nurses' Health Study, most traditional CVD risk factors were similar between those who had RA and those who did not. However, as expected, biomarkers of inflammation associated with CVD were generally elevated in women with RA.
12516572 Glycosylation of type II collagen is of major importance for T cell tolerance and patholog 2002 Dec Type II collagen (CII) is a candidate cartilage-specific autoantigen, which can become post-translationally modified by hydroxylation and glycosylation. T cell recognition of CII is essential for the development of murine collagen-induced arthritis (CIA) and also occurs in rheumatoid arthritis (RA). The common denominator of murine CIA and human RA is the presentation of an immunodominant CII-derived glycosylated peptide on murine Aq and human DR4 molecules, respectively. To investigate the importance of T cell recognition of glycosylated CII in CIA development after immunization with heterologous CII, we treated neonatal mice with different heterologous CII-peptides (non-modified, hydroxylated and galactosylated). Treatment with the galactosylated peptide (galactose at position 264) was superior in protecting mice from CIA. Protection was accompanied by a reduced antibody response to CII and by an impaired T cell response to the glycopeptide. To investigate the importance of glycopeptide recognition in an autologous CIA model, we treated MMC-transgenic mice, which express the heterologous CII epitope with a glutamic acid in position 266 in cartilage, with CII-peptides. Again, a strong vaccination potential of the glycopeptide was seen. Hence CII-glycopeptides may be the optimal choice of vaccination target in RA, since humans share the same epitope as the MMC mouse.
15188379 Local activation of STAT-1 and STAT-3 in the inflamed synovium during zymosan-induced arth 2004 Jun OBJECTIVE: STAT proteins play an important role in cytokine signaling. Some investigators have reported preferential activation of STAT-1, and others have reported preferential activation of STAT-3, in response to endogenous interleukin-6 (IL-6), in patients with rheumatoid arthritis. The present study was undertaken to investigate synovial STAT-1 and STAT-3 activation in an experimental animal model of arthritis. METHODS: Zymosan was injected intraarticularly into naive wild-type (WT), IL-6(-/-), and STAT-1(-/-) mice to induce arthritis. Western blots of synovial lysates were probed with phosphospecific antibodies to detect STAT-1/STAT-3 activation. Inflammation was assessed histologically. Synovial gene expression of the STAT-induced feedback inhibitors suppressor of cytokine signaling 1 (SOCS-1) and SOCS-3 in WT and STAT-1(-/-) mice was investigated by reverse transcriptase-polymerase chain reaction. RESULTS: STAT-3 was activated in inflamed synovium of WT mice throughout the course of disease, whereas activated STAT-1 was observed only during the chronic phase. In IL-6(-/-) mice, STAT activation was limited to STAT-3 on day 1. Although macrophage influx was not inhibited, disease went into remission after day 7 in IL-6(-/-) mice. STAT-1 deficiency resulted in exacerbation of chronic joint inflammation and granuloma formation. In STAT-1(-/-) mice, STAT-3 activation in the inflamed joints was unaltered as compared with WT mice. However, synovial SOCS-1, but not SOCS-3, gene expression was markedly reduced in STAT-1(-/-) mice. CONCLUSION: The results in the IL-6(-/-) mice suggest that STAT-3 is involved in the chronicity of ZIA. Exacerbation of arthritis in STAT-1(-/-) mice suggests an opposing effect of STAT-1, i.e., suppression of joint inflammation. The expression of SOCS-1 could be the underlying mechanism by which STAT-1 controls joint inflammation.