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ID PMID Title PublicationDate abstract
19208589 CD153 in rheumatoid arthritis: detection of a soluble form in serum and synovial fluid, an 2009 Mar OBJECTIVE: A CD30-CD153 mast cell axis has been described in skin inflammations and Hodgkin's lymphoma. We investigated if a soluble form of CD153 is present in the serum and synovial fluid (SF) of patients with rheumatoid arthritis (RA), and determined whether mast cells express CD153 in the synovium of these patients. METHODS: Soluble forms of CD30 and CD153 were quantified in serum and SF of patients with RA by ELISA. Consecutive sections of synovial biopsies from 12 patients were stained against tryptase (mast-cell marker), CD30, and CD153. RESULTS: Elevated concentrations of the soluble form of CD153 were found in serum from 14/15 RA patients. In the SF, 11/20 patients had detectable levels of soluble CD153. CD30 and CD153 were expressed in all biopsies that were studied. Mast cells were present in all the synovial biopsies, and expressed CD153 in one-third of the cases. CONCLUSION: We observed that CD153 was expressed in the synovium of patients with RA and we were able to correlate the serum levels of soluble CD153 with SF levels in the same patients. Because CD30 can activate mast cells to release chemokines without degranulation, our finding that mast cells express CD153 in RA synovium raises the possibility that a CD30-CD153 axis may contribute to the activation of synovial mast cells in the absence of degranulation.
20659411 Reelin levels are increased in synovial fluid of patients with rheumatoid arthritis. 2010 Jul OBJECTIVES: To evaluate the presence and the glycosylation pattern of reelin in synovial fluid and serum of patients affected by different rheumatic pathologies. METHODS: Reelin levels were evaluated in patients affected by rheumatoid arthritis (RA), psoriatic arthritis (PsA), spondyloarthritis (SpA) and osteoarthritis (OA). Reelin semi-quantitative assays were performed by western blot. The glycosylation pattern was evaluated by immunoblotting performed by sepharose conjugated lectins. RT-PCR was used to detect the presence of mRNA encoding for reelin and its receptors. RESULTS: Reelin is detectable in both sinovial fluids and sera and its levels are more elevated in patients affected by RA with respect to those affected by other inflammatory and non inflammatory joint diseases. The glycosylation pattern of the protein differs in synovial fluid and serum. Fibroblast-like synoviocytes (FLS) express the mRNAs encoding for reelin and its receptors. CONCLUSIONS: Since its levels are higher in RA then in the other analysed pathologies, reelin can represent a candidate suitable for the differential diagnosis of this pathology. Moreover, the observation that this protein is encoded by FLS and differentially glycosylated in blood and synovial fluid supports the hypothesis that it is locally produced in the joints, where it could play an important role in RA development and maintenance.
19219643 Correlation between synovial blood flow signals and serum vascular endothelial growth fact 2009 The objective of the study is to examine the relationship between synovial blood flow signals and vascular endothelial growth factor (VEGF) involved in angiogenesis by Doppler ultrasound. Twenty-one patients meeting the diagnostic criteria of the American College of Rheumatology (ACR) were enrolled in this study. Doppler ultrasound signals of blood flow in the wrist synovial membrane were measured and classified into three grades: grade 1 = no flow; grade 2 = mild flow; grade 3 = intense flow. A significant correlation was observed between blood flow signals in the wrist synovial membrane and serum VEGF levels (r = 0.5681, P = 0.0072). These results suggest that the measurement of Doppler ultrasound signals of blood flow in the wrist synovial membrane is useful in the evaluation of angiogenesis.
20814812 Immunochemical studies on catechol-estrogen modified plasmid: possible role in rheumatoid 2011 Feb INTRODUCTION: Increased concentrations of estrogen metabolites (catecholestrogens) have been found in rheumatoid arthritis (RA) but the exact patho-etiology remains elusive. METHODS: The binding of antibodies from the sera of RA patients and control subjects to native and modified DNA was studied by direct binding and inhibition ELISA, quantitative precipitin titration. Experimentally induced antibodies were also checked to detect oxidative lesions in the DNA as well as for the estimation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in different fluids of RA. RESULTS: Anti-DNA IgG from RA sera, exhibited increased recognition of modified DNA than native DNA (nDNA; P < 0.001). The relative affinity of anti-DNA antibodies for modified and nDNA was in the order of 1.85 × 10(-7), 1.23 × 10(-7), and 1.2 × 10(-6). Samples of DNA from RA patients showed a significant inhibition in the induced antibody activity in comparison to DNA isolates from controls (P < 0.001). The concentration of 8-OHdG evaluated by induced antibody in RA patients was found to be significantly higher than controls ((P < 0.0001, P < 0.01, P < 0.05). CONCLUSION: High binding of modified DNA with the IgG from RA patient might explain possible antigenic role of 4-OHE(2)-modified DNA in the production of anti-DNA antibodies. In addition, the induced antibodies have been shown to represent an alternative immunochemical probe to detect oxidative lesions in DNA as well as for the estimation of 8-OHdG levels in different body fluid of RA patients, which may be used as marker in the diagnosis of the disease.
19779763 Usefulness and limitations of QuantiFERON-TB Gold in Japanese rheumatoid arthritis patient 2010 Feb We aimed to determine the sensitivity and specificity of QuantiFERON-TB Gold (QFT-G) in Japanese rheumatoid arthritis (RA) patients with a past history of tuberculosis (TB). We assessed whether it is possible to decrease the cutoff using receiver operating characteristic (ROC) analysis. We evaluated chest computed tomography (CT) findings, prior history of treatment, and contact with active TB in 370 RA patients. Forty-nine patients before initiation of treatment with tumor necrosis factor (TNF) inhibitors were divided into two groups: 22 with a past history of TB and 27 without. We estimated the efficacy of QFT-G compared with the tuberculin skin test and antituberculosis (anti-TB) glycolipid antigen antibody. QFT-G was positive (>or=0.35 IU/ml) in 13.6% with a past history of TB, increasing to 27.3% at the intermediate range cutoff of 0.1 IU/ml. The sensitivity and specificity of QFT-G was 0.27 and 1.00, respectively, at 0.1 IU/ml. Using ROC analysis, the area under the curve (AUC) of QFT-G but not for the other two tests was significantly large. QFT-G is a useful diagnostic method due to its superior specificity, but the use of a cutoff value of 0.35 IU/ml will likely result in an underestimate. We propose that a lower interferon-gamma (IFN-gamma) titer of 0.1 IU/ml be adopted when deciding to administer anti-TB drugs before initiation of TNF inhibitors.
19506882 Third generation anti-cyclic citrullinated peptide antibodies do not predict anti-TNF-alph 2010 Feb Objective of this study is to retrospectively compare the third generation anti-cyclic citrullinated peptide (anti-CCP3) test with the second generation (anti-CCP2) assay as markers of disease activity and predictors of clinical response in rheumatoid arthritis (RA) patients treated with TNF-alpha blocking agents. This study was performed in 42 RA patients treated either with infliximab (n = 11), etanercept (n = 7) or adalimumab (n = 24). Serum anti-CCP3 and anti-CCP2 levels were tested before and 6 months after starting a TNF-alpha blocking treatment using commercially available ELISA kits. Anti-CCP3 and anti-CCP2 antibody levels did not significantly change after 6 months of TNF-alpha blocking treatment. Furthermore, neither anti-CCP3 nor anti-CCP2 was useful to predict anti-TNF-alpha treatment response using receiving operating characteristic curve and logistic regression analyses. Both anti-CCP3 and anti-CCP2 are not differentially influenced by TNF-alpha blocking agents in RA patients and failed to predict anti-TNF-alpha treatment response.
20439289 The ACPA isotype profile reflects long-term radiographic progression in rheumatoid arthrit 2010 Jun BACKGROUND: The presence of anti-citrullinated protein antibodies (ACPA) is a powerful predictive factor for the development and progression of rheumatoid arthritis (RA). The ACPA response has been shown to consist of various isotypes, but the consequences of differences in isotype distribution have not been extensively investigated. OBJECTIVE: To investigate the relationship between ACPA isotypes, disease progression and radiological outcome. METHODS: ACPA isotypes were determined in sera of anti-cyclic citrullinated peptide 2-positive patients by enzyme-linked immunosorbent assay (ELISA). To investigate whether the ACPA response continues to evolve during disease development, the ACPA isotype profile during progression of undifferentiated arthritis (UA) to RA was studied. The association of disease progression with ACPA isotype use was assessed using long-term radiographic follow-up data from patients with RA in two independent cohorts. RESULTS: The ACPA isotype distribution did not expand during disease progression from UA to RA, but was relatively stable over time. In both RA cohorts, the baseline ACPA isotype profile was a significant predictor of disease severity, with more isotypes indicating a higher risk of radiographic damage (odds ratio for every additional isotype: 1.4 (95% CI 1.1 to 1.9) p<0.001). ACPA isotypes supplied additional prognostic information to ACPA status alone, even after correction for other predictive factors. CONCLUSIONS: The magnitude of the ACPA isotype profile at baseline reflects the risk of future radiographic damage. These results indicate that the presence and the constitution of the ACPA response are relevant to the disease course of RA.
20235183 Validity of ultrasonography and measures of adult shoulder function and reliability of ult 2010 Aug OBJECTIVE: To assess the intra- and interobserver reproducibility of musculoskeletal ultrasonography (US) in detecting inflammatory shoulder changes in patients with rheumatoid arthritis, and to determine the agreement between US and the Shoulder Pain and Disability Index (SPADI) and the Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire, using magnetic resonance imaging (MRI) as a gold standard. METHODS: Eleven rheumatologists investigated 10 patients in 2 rounds independently and blindly of each other by US. US results were compared with shoulder function tests and MRI. RESULTS: The positive and negative predictive values (NPVs) for axillary recess synovitis (ARS) were 0.88 and 0.43, respectively, for posterior recess synovitis (PRS) were 0.36 and 0.97, respectively, for subacromial/subdeltoid bursitis (SASB) were 0.85 and 0.28, respectively, and the NPV for biceps tenosynovitis (BT) was 1.00. The intraobserver kappa was 0.62 for ARS, 0.59 for PRS, 0.51 for BT, and 0.70 for SASB. The intraobserver kappa for power Doppler US (PDUS) signal was 0.91 for PRS, 0.77 for ARS, 0.94 for SASB, and 0.53 for BT. The interobserver maximum kappa was 0.46 for BT, 0.95 for ARS, 0.52 for PRS, and 0.61 for SASB. The interobserver reliability of PDUS was 1.0 for PRS, 0.1 for ARS, 0.5 for BT, and 1.0 for SASB. P values for the SPADI and DASH versus cuff tear on US were 0.02 and 0.01, respectively; all other relationships were not significant. CONCLUSION: Overall agreements between gray-scale US and MRI regarding synovitis of the shoulder varied considerably, but excellent results were seen for PDUS. Measures of shoulder function have a poor relationship with US and MRI. Improved standardization of US scanning technique could further reliability of shoulder US.
19633797 Switching between TNFalpha antagonists in rheumatoid arthritis: personal experience and re 2009 Apr OBJECTIVE: To evaluate the clinical response after switching to another TNFalpha antagonist in patients with rheumatoid arthritis (RA) and provide a review of the literature on this topic. METHODS: In this ongoing, longitudinal, observational study we have prospectively collected data of patients starting biological treatments since 2000. The present analysis is restricted to RA patients who switched to another anti-TNFalpha due to lack of efficacy (LaE), loss of efficacy (LoE), or adverse events (AEs) by the end of December 2007. Disease activity score (ESR-based DAS28) was calculated and the clinical response (none, moderate, good) was evaluated according to the European League Against Rheumatism (EULAR) criteria. Clinical remission (DAS28 <2.6) and low disease activity (DAS28
18723564 Serum IgG antibodies to peptidylarginine deiminase 4 predict radiographic progression in p 2009 Feb BACKGROUND: Peptidylarginine deiminase 4 (PAD4) may generate epitopes targeted by anticitrullinated protein antibodies in rheumatoid arthritis (RA). A subset of patients with RA has serum autoantibodies to human recombinant PAD4 (hPAD4). Here, we assessed whether anti-hPAD4 status in RA predicted disease outcome after antitumour necrosis factor (anti-TNF)-alpha therapy. METHODS: We analysed RA sera obtained at baseline (n = 40) and after 1 year on anti-TNF-alpha therapy (n = 33) for anti-hPAD4 IgG. Association analyses between baseline anti-hPAD status and disease progression were performed. RESULTS: We found that 17 of 40 patients (42.5%) were serum anti-hPAD4 positive at baseline, and the anti-hPAD4 IgG levels were stable over 1 year on anti-TNF-alpha therapy. At baseline, there were indications that anti-hPAD4 positive patients had more severe disease than the negative patients. After 1 year on anti-TNF-alpha therapy, the anti-hPAD4 positive patients displayed a persistently elevated disease activity score using 28 joint counts score and increased progression in the van der Heijde-modified Sharp erosion score. Accordingly, more anti-hPAD4 positive than negative patients presented an increase in van der Heijde-modified Sharp erosion scores >0 over 1 year. CONCLUSIONS: Anti-hPAD4 IgG can be detected in a subset of RA sera and the levels are stable after initiation of anti-TNF-alpha therapy. Serum anti-hPAD4 may predict persistent disease activity and radiographic progression in patients with RA receiving anti-TNF-alpha therapy.
19798035 Rejuvenating the immune system in rheumatoid arthritis. 2009 Oct In rheumatoid arthritis (RA), the aging process of the immune system is accelerated. Formerly, this phenomenon was suspected to be a consequence of chronic inflammatory activity. However, newer data strongly suggest that deficiencies in maintaining telomeres and overall DNA stability cause excessive apoptosis of RA T cells, imposing proliferative pressure and premature aging on the system. Already during the early stages of their life cycle, and long before they participate in the inflammatory process, RA T cells are lost owing to increased apoptotic susceptibility. A search for underlying mechanisms has led to the discovery of defective pathways of repairing broken DNA and elongating and protecting telomeric sequences at the chromosomal ends. Two enzymatic machineries devoted to DNA repair and maintenance have been implicated. RA T cells fail to induce sufficient amounts of the telomeric repair enzyme telomerase, leaving telomeric ends uncapped and thus susceptible to damage. Of equal importance, RA T cells produce low levels of the DNA repair enzyme ataxia telangiectasia mutated and the complex of nucleoproteins that sense and fix DNA double-strand breaks. The inability to repair damaged DNA renders naive T cells vulnerable to apoptosis, exhausts T-cell regeneration and reshapes the T cell repertoire. Therapeutic attempts to reset the immune systems of patients with RA and prevent premature immunosenescence should include restoration of DNA repair capability.
19363022 Effect of dexamethasone on autoantibody levels and arthritis development in patients with 2010 Mar BACKGROUND: Rheumatoid arthritis is characterised by antibodies to citrullinated proteins (ACPA) and rheumatoid factor (RF) in the preclinical phase. OBJECTIVE: To determine whether an intervention aimed at decreasing autoantibody levels in people at risk may be effective in preventing progression to arthritis. METHODS: 83 patients with arthralgia positive for ACPA or IgM-RF were randomly allocated to intramuscular injections of 100 mg dexamethasone or placebo at baseline and 6 weeks. The primary end point was a 50% antibody reduction or normalisation at 6 months. RESULTS: The primary end point was reached in one patient in each group. Patients treated with dexamethasone had reductions of antibody levels after 1 month (ACPA 222% and IgM-RF 214%), which persisted at 6 months for ACPA. During a median follow-up of 26 months, arthritis development in both groups was similar (20% vs 21%). CONCLUSION: In autoantibody-positive patients with arthralgia, dexamethasone treatment decreases ACPA and IgM-RF levels, but does not prevent arthritis development. TRIAL REGISTRATION NUMBER: ISRCTN73232918.
19211305 Screening of tuberculosis by interferon-gamma assay before biologic therapy for rheumatoid 2009 Mar Infection with Mycobacterium tuberculosis (M. tuberculosis) is a critical complication in anti-TNF therapies. In 141 BCG vaccinated healthy individuals and 71 rheumatoid arthritis (RA) patients as screening before anti-TNF therapies, M. tuberculosis specific immune responses were evaluated by tuberculin skin test (TST) and enzyme-linked immunospot assay (ELISPOT), which detected antigen specific IFN-gamma secreting cells in peripheral blood mononuclear cells simulated with either purified protein derivative (PPD), early secretory antigen target 6 (ESAT-6) or culture filtrate protein 10 (CFP-10). Induration over 5 mm in TST was found in 87.9% of controls and 21.4% of RA patients. Erythema size in TST was significantly suppressed in RA patients, especially those receiving prednisolone (PSL), whereas the PPD specific IFN-gamma secretion was less attenuated. Significant responses to either ESAT-6 or CFP-10 in ELISPOT were detected in 14.1% of RA patients including those having positive TST, while the ELISPOT assay was negative in all healthy individuals and 73.3% of RA patients having positive TST. Of ELISPOT positive RA patients, mean dosage of PSL was 4.58 mg and 1.25 mg in TST negative and positive patients, respectively. Thus, ELISPOT is useful for screening of tuberculosis in RA patients, even in those receiving corticosteroids.
19449010 Late infection of total knee arthroplasty inflamed by anti-TNFalpha, Infliximab therapy in 2010 Jan We report a case of sudden onset of late infection after TKA inflamed by anti-TNFalpha therapy, Infliximab, in a 54-year-old woman with RA. Infliximab therapy was started 3 years and 8 months after TKAs as a result of multiple arthritides showing high inflammation of RA. One week after the third administration of Infliximab, the patient suffered sudden knee pain and infectious clinical symptoms, and bacteria (MSSA) were detected by joint effusion culture. She was successfully treated by open debridement with antibiotics-loaded calcium phosphate bone paste and cement and the prostheses were retained. Early diagnosis and operative treatment might be the key to controlling infected TKA without removing the implant. This present case might indicate a serious risk of immunosuppressive effects caused by Infliximab.
19487261 Association of severe inflammatory polyarthritis in primary Sjögren's syndrome: clinical, 2009 Sep OBJECTIVE: To evaluate the clinical, serologic, and MHC class II antigen characteristics of a group of patients with primary Sjögren's syndrome (SS) and severe arthritis. METHODS: A case-control study comparing 35 patients with primary SS: 17 with inflammatory arthritis, 18 without arthritis. RESULTS: All patients fulfilled criteria for primary SS. There were no demographic or clinical features other than inflammatory arthritis, often erosive, that distinguished patients with arthritis from those without. All patients had anti-Ro/SSA autoantibodies, most had anti-La/SSB autoantibodies, and a high percentage of these patients had anti-citrullinated peptide antibodies absent in those without inflammatory arthritis. HLA typing revealed that most patients with anti-citrulline antibodies expressed MHC class II molecules with the shared epitope (SE). The presence of DRB1*0301 linked to the expression of anti-Ro/SSA autoantibodies did not influence the level or frequency of anti-citrulline antibodies in these patients. CONCLUSION: Severe arthritis with features resembling rheumatoid arthritis including erosive disease can occur in primary SS, particularly among those with anti-citrulline antibodies and the SE.
18684745 Non-inherited maternal human leukocyte antigen alleles in susceptibility to familial rheum 2009 Jan OBJECTIVES: Some patients with rheumatoid arthritis (RA) lack RA-associated human leukocyte antigen (HLA) alleles. Prior studies investigated non-inherited maternal HLA alleles (NIMA) in RA risk with conflicting results. METHODS: We examined NIMA in a large cohort of families from the North American Rheumatoid Arthritis Consortium (NARAC). RESULTS: Among 620 patients with 1 or both parents having a HLA genotype, patients with RA informative for analysis included 176 without HLA-DRB1*04 and 86 without the HLA shared epitope (SE). The frequency of NIMA encoding HLA-DR4 or the SE was compared to the non-inherited paternal allele (NIPA). DR4-encoding NIMA vs NIPA revealed no significant difference (27% vs 20%). However, parity is known to modulate RA risk and analyses stratified by sex and age of onset showed significant variation among women. Interestingly, among women with onset <45 years DR4-encoding NIMA was increased compared to NIPA; among women > or =45 years at onset the reverse was observed (31% vs 16% compared to 10% vs 60%, p = 0.008). DR4 encoding NIMA vs NIPA did not differ in men. The SE did not differ in men or women. CONCLUSIONS: Risk of RA was associated with HLA-DR4 encoding NIMA in younger-onset women but not in older-onset women or men. These observations could help explain conflicting prior results of NIMA in RA.
19216559 Comparative effects of two gingerol-containing Zingiber officinale extracts on experimenta 2009 Mar 27 Ginger (Zingiber officinale) supplements are being promoted for arthritis treatment in western societies on the basis of ginger's traditional use as an anti-inflammatory in Chinese and Ayurvedic medicine. However, scientific evidence of ginger's antiarthritic effects is sparse, and its bioactive joint-protective components have not been identified. Therefore, the ability of a well-characterized crude ginger extract to inhibit joint swelling in an animal model of rheumatoid arthritis, streptococcal cell wall-induced arthritis, was compared to that of a fraction containing only gingerols and their derivatives. Both extracts were efficacious in preventing joint inflammation. However, the crude dichloromethane extract, which also contained essential oils and more polar compounds, was more efficacious (when normalized to gingerol content) in preventing both joint inflammation and destruction. In conclusion, these data document a very significant joint-protective effect of these ginger samples and suggest that nongingerol components are bioactive and can enhance the antiarthritic effects of the more widely studied gingerols.
20461039 Clinical output of the rheumatoid cervical spine in patients with mutilating-type joint in 2010 Jun 1 STUDY DESIGN: Retrospective study. OBJECTIVE: To gain an insight for the final clinical output of surgically managed cervical lesions in seropositive rheumatoid arthritis (RA) patients with mutilating-type joint involvement (mutilating-RA patients), these patients was followed up until either death or complete bedridden. SUMMARY OF BACKGROUND DATA: There has been no study reporting the final clinical output of surgically managed cervical lesion in mutilating-RA patients. In our previous study, we reported short- to middle-term result of such patient. The present study further traced those patients and reports the final clinical output. METHODS: Seventeen seropositive mutilating-RA patients extracted from 504 RA patients were enrolled. Eleven patients underwent surgical treatments, whereas six patients did not. All patients, who underwent operation, have received occipitocervical or occipitocervicothoracic fusion. Neck pain, neurological symptoms and ADL score were completely followed up (i.e., follow-up period>10 years). RESULTS: The six patients of non-operated group worsened ADL score and resulted in either complete bedridden or death within 3 years. Contrary, 11 operated patients either improved or maintained ADL until their death. Survival rate in 6.2 years was 0% in non-operated group and 27% in operated group, respectively. The present study suggests that the seropositive mutilating-RA patients worsen cervical lesions once they become affected, and are likely to lose their ADL activity. CONCLUSION: Once seropositive mutilating-RA patients develop major spinal involvement(s), they are likely to undergo a life-threatening stage of the disease during the next 5-10 years. Surgical intervention is advocated not only to treat the neurological compromise but also to sustain their ADL levels during end stage of disease. The sustained ADL, in turn, may contribute to the longevity of these patients by preventing other major life-threatening events.
19443979 Desquamative interstitial pneumonia (DIP) in a patient with rheumatoid arthritis: is DIP a 2009 Desquamative interstitial pneumonia (DIP) is a rare pattern of diffuse parenchymal lung disease known as one of the idiopathic interstitial pneumonias and is considered to be a smoking- or dust inhalation-related interstitial pneumonia in the majority of cases. This report presents the first case of DIP in which the pulmonary manifestation preceded the onset of rheumatoid arthritis. This case and our review of twenty-four DIP cases (nineteen cases previously-reported from Japan, plus five cases in our departments) indicate the possibility that the DIP pattern is an additional form of diffuse interstitial pneumonia that may develop in association with autoimmune diseases.
19198229 [A case of cryptococcal pneumonia accompanying meningitis]. 2009 Jan Cryptococcosis is a fungal infection caused by cryptococcus neoformans. Cryptococcal pneumonia occurs due to inhalation of the organism into the respiratory tract, sometimes accompanied by meningitis in immunocompromised patients, and can be life-threatening. We report a case of cryptococcal meningitis occurring during corticosteroid therapy for rheumatoid arthritis. CASE: A 82-year-old woman with rheumatoid arthritis was given a diagnosis of cryptococcal meningitis, and improved after administeration of amphotericin B in combination with flucytosine. However 3 weeks later, side effects occurred, she was given fluconazole alone, but her condition worsened and she died. In severe cases of cryptococcal meningitis, we should take into account drug susceptibility tests and drug concentrations at the site of infection.