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ID PMID Title PublicationDate abstract
22323686 Predictors of mortality after total knee replacement: a ten-year survivorship analysis. 2012 Feb We report the general mortality rate after total knee replacement and identify independent predictors of survival. We studied 2428 patients: there were 1127 men (46%) and 1301 (54%) women with a mean age of 69.3 years (28 to 94). Patients were allocated a predicted life expectancy based on their age and gender. There were 223 deaths during the study period. This represented an overall survivorship of 99% (95% confidence interval (CI) 98 to 99) at one year, 90% (95% CI 89 to 92) at five years, and 84% (95% CI 82 to 86) at ten years. There was no difference in survival by gender. A greater mortality rate was associated with increasing age (p < 0.001), American Society of Anesthesiologists (ASA) grade (p < 0.001), smoking (p < 0.001), body mass index (BMI) < 20 kg/m(2) (p < 0.001) and rheumatoid arthritis (p < 0.001). Multivariate modelling confirmed the independent effect of age, ASA grade, BMI, and rheumatoid disease on mortality. Based on the predicted average mortality, 114 patients were predicted to have died, whereas 217 actually died. This resulted in an overall excess standardised mortality ratio of 1.90. Patient mortality after TKR is predicted by their demographics: these could be used to assign an individual mortality risk after surgery.
21345937 Rasch analysis of Dutch-translated version of the Foot Impact Scale for rheumatoid arthrit 2011 Jul OBJECTIVE: To translate the foot impact scale for RA (FIS-RA) to the dutch target language and to evaluate its internal construct validity using rasch analysis. METHODS: Forward and backward translations of the original English version of the FIS-RA scale, combined with synthesis techniques and expert committee review, were undertaken to produce a final Dutch version with two subscales for impairment/footwear (FIS-RA(IF)) and activity/participation (FIS-RA(AP)). The pre-final version was field tested in RA patients to investigate face and content validity. FIS-RA questionnaires were completed by 207 Dutch RA patients. Rasch analysis tested the data for overall fit to the model, item and person fit, unidimensionality, differential item function (DIF) by age, gender and disease duration, targeting, reliability and local response dependency. Item deletion and re-analysis were planned, where Rasch model assumptions were violated. RESULTS: The FIS-RA(IF) (P < 0.0001) and FIS-RA(AP) (P < 0.0001) subscales did not fit the overall Rasch model. Misfitting items, DIF by age, gender and disease duration, and local response dependency were observed in both subscales. Item thresholds showed good coverage over both scales although a floor effect was observed for the FIS-RA(AP) subscale. The person separation index was 0.81 and 0.92 for the FIS-RA(IF) and FIS-RA(AP) subscales, respectively. Both subscales were not unidimensional. Item deletion and repeat Rasch analysis produced two subscales that fitted the Rasch model and were unidimensional. CONCLUSION: A Dutch language version of the FIS-RA questionnaire was successfully developed using Rasch analysis. Subscales for impairment/footwear and activity/participation showed good construct validity and were unidimensional.
22124512 Disability of the Arm, Shoulder and Hand questionnaire in Swedish patients with rheumatoid 2012 Jan OBJECTIVE: The aim of this study was to assess the reliability and validity of the Disability of the Arm, Shoulder and Hand (DASH) questionnaire in a Swedish rheumatoid arthritis population. METHODS: To investigate the concurrent and convergent validity, 67 patients with rheumatoid arthritis completed the DASH, the Health Assessment Questionnaire Disability Index (HAQ) and activity-induced pain. Active shoulder-arm motion, handgrip force and disease activity (Disease Activity Score in 28 joints; DAS28) were assessed. The test-retest reliability was investigated in 26 patients. Face validity was also investigated. RESULTS: Spearman's correlation coefficient revealed a significant association (p
21305508 In vivo effects of the anti-interleukin-6 receptor inhibitor tocilizumab on the B cell com 2011 May OBJECTIVE: Interleukin-6 (IL-6) receptor inhibition by tocilizumab was recently licensed for the treatment of rheumatoid arthritis (RA). IL-6 induces in vitro differentiation of B cells into antibody-forming cells; however, the in vivo effects of IL-6 inhibition on the B cell compartment are currently not known. The purpose of this study was to examine this feature. METHODS: Sixteen patients with active RA were treated in an open-label study with tocilizumab (8 mg/kg every 4 weeks). Immunophenotyping was performed at baseline, week 12, and week 24. RESULTS: Memory B cell subsets declined significantly during tocilizumab therapy. Preswitch memory B cells decreased from a median of 19.6% to 12.3% at week 24 and postswitch memory B cells declined from a median of 18.6% to 15.0% at week 24 (P = 0.04). In parallel, CD19+IgA+ and CD19+IgG+ B cells decreased significantly. The proportion of IgA-expressing B cells fell from a median of 9.2% at baseline to 4.3% at week 12 and to 3.6% at week 24 (P = 0.01). IgG+ B cells declined from a median of 6.7% at baseline to 4.9% at week 12 (P = 0.007) and 2.8% at week 24 (P = 0.01). In parallel, serum levels of IgA and IgG were significantly diminished at week 24 (P < 0.05). There was a good correlation between relative and absolute numbers of IgA+ B cells with serum IgA at week 24. CONCLUSION: Tocilizumab induced a significant reduction in the frequency of peripheral preswitch and postswitch memory B cells. In addition, the number of IgG+ and IgA+ B cells declined and correlated well with reduced serum immunoglobulin levels. The data indicate that IL-6 blockade affects the B cell hyperreactivity in RA patients.
22451032 Interleukin-6 and cytochrome-P450, reason for concern? 2012 Sep Interleukin 6 (IL-6) plays a central role in the immunopathogenesis of rheumatoid arthritis (RA) and tocilizumab [TCZ] (an anti-IL-6 receptor antibody) has been shown to be effective in the treatment of the condition. As up-regulation of IL-6 reduces the activity of cytochrome P450 (CYP) enzymes, blockade of this cytokine may enhance CYP function. This may lead to reduced bioavailability of CYP-metabolized drugs. Due to the increasing use of TCZ, we undertook a systematic literature review to explore such interactions. Our search was conducted in MEDLINE, EMBASE, Web of Science, FDA and EMEA websites for in vitro and in vivo studies, clinical trials and reviews mentioning TCZ and CYP on the basis of the title and abstract. Appropriate articles were further screened based on full-text review to select only those reporting IL-6, TCZ and their potential interaction with CYP-metabolized drugs. Two in vitro studies showed that TCZ-reversed IL-6 induced reduction of CYP isozymes. CYP3A4 mRNA expression was most reduced by IL-6 followed by CYP2C9 and CYP2C19. This change was prevented with TCZ. Three clinical studies investigated the interaction showing simvastatin (CYP3A4 substrate) bioavailability reduced by TCZ and omeprazole bioavailability was decreased by TCZ-induced CYP2C19 activity. The bioavailability of dextromethorphan (CYP2D6 and CYP3A4 substrates) was shown to be unaffected by TCZ treatment. The observed increase in CYP isozyme activity by TCZ is of clinical relevance as the bioavailability of the CYP isozyme substrates were decreased in vivo. As CYP3A4 is the isozyme responsible for the largest proportion of drug metabolism, it is probable that the bioavailability of other drugs may be reduced by TCZ. Thus, clinicians should exercise caution when co-prescribing TCZ and CYP-metabolized drugs. More studies are required to investigate this interaction further.
21767392 Association of acid phosphatase locus 1*C allele with the risk of cardiovascular events in 2011 Jul 18 INTRODUCTION: Acid phosphatase locus 1 (ACP1) encodes a low molecular weight phosphotyrosine phosphatase implicated in a number of different biological functions in the cell. The aim of this study was to determine the contribution of ACP1 polymorphisms to susceptibility to rheumatoid arthritis (RA), as well as the potential contribution of these polymorphisms to the increased risk of cardiovascular disease (CV) observed in RA patients. METHODS: A set of 1,603 Spanish RA patients and 1,877 healthy controls were included in the study. Information related to the presence/absence of CV events was obtained from 1,284 of these participants. All individuals were genotyped for four ACP1 single-nucleotide polymorphisms (SNPs), rs10167992, rs11553742, rs7576247, and rs3828329, using a predesigned TaqMan SNP genotyping assay. Classical ACP1 alleles (*A, *B and *C) were imputed with SNP data. RESULTS: No association between ACP1 gene polymorphisms and susceptibility to RA was observed. However, when RA patients were stratified according to the presence or absence of CV events, an association between rs11553742*T and CV events was found (P = 0.012, odds ratio (OR) = 2.62 (1.24 to 5.53)). Likewise, the ACP1*C allele showed evidence of association with CV events in patients with RA (P = 0.024, OR = 2.43). CONCLUSIONS: Our data show that the ACP1*C allele influences the risk of CV events in patients with RA.
21714856 Disease activity and low physical activity associate with number of hospital admissions an 2011 Jun 29 INTRODUCTION: Substantial effort has been devoted for devising effective and safe interventions to reduce preventable hospital admissions in chronic disease patients. In rheumatoid arthritis (RA), identifying risk factors for admission has important health policy implications, but knowledge of which factors cause or prevent hospital admissions is currently lacking. We hypothesised that disease activity/severity and physical activity are major predictors for the need of hospitalisation in patients with RA. METHODS: A total of 244 RA patients were assessed for: physical activity (International Physical Activity Questionnaire), RA activity (C-reactive protein: CRP; disease activity score: DAS28) and disability (Health Assessment Questionnaire: HAQ). The number of hospital admissions and length of hospitalisation within a year from baseline assessment were collected prospectively. RESULTS: Disease activity and disability as well as levels of overall and vigorous physical activity levels correlated significantly with both the number of admissions and length of hospitalisation (P < 0.05); regression analyses revealed that only disease activity (DAS28) and physical activity were significant independent predictors of numbers of hospital admissions (DAS28: (exp(B) = 1.795, P = 0.002 and physical activity: (exp(B) = 0.999, P = 0.046)) and length of hospitalisation (DAS28: (exp(B) = 1.795, P = 0.002 and physical activity: (exp(B) = 0.999, P = 0.046). Sub-analysis of the data demonstrated that only 19% (n = 49) of patients engaged in recommended levels of physical activity. CONCLUSIONS: This study provides evidence that physical activity along with disease activity are important predictors of the number of hospital admissions and length of hospitalisation in RA. The combination of lifestyle changes, particularly increased physical activity along with effective pharmacological therapy may improve multiple health outcomes as well as cost of care for RA patients.
21690378 MicroRNA-155 as a proinflammatory regulator in clinical and experimental arthritis. 2011 Jul 5 MicroRNA (miRNA) species (miR) regulate mRNA translation and are implicated as mediators of disease pathology via coordinated regulation of molecular effector pathways. Unraveling miR disease-related activities will facilitate future therapeutic interventions. miR-155 recently has been identified with critical immune regulatory functions. Although detected in articular tissues, the functional role of miR-155 in inflammatory arthritis has not been defined. We report here that miR-155 is up-regulated in synovial membrane and synovial fluid (SF) macrophages from patients with rheumatoid arthritis (RA). The increased expression of miR-155 in SF CD14(+) cells was associated with lower expression of the miR-155 target, Src homology 2-containing inositol phosphatase-1 (SHIP-1), an inhibitor of inflammation. Similarly, SHIP-1 expression was decreased in CD68(+) cells in the synovial lining layer in RA patients as compared with osteoarthritis patients. Overexpression of miR-155 in PB CD14(+) cells led to down-regulation of SHIP-1 and an increase in the production of proinflammatory cytokines. Conversely, inhibition of miR-155 in RA synovial CD14(+) cells reduced TNF-α production. Finally, miR-155-deficient mice are resistant to collagen-induced arthritis, with profound suppression of antigen-specific Th17 cell and autoantibody responses and markedly reduced articular inflammation. Our data therefore identify a role of miR-155 in clinical and experimental arthritis and suggest that miR-155 may be an intriguing therapeutic target.
22052738 Enhancement of the inhibitory effect of an IL-15 antagonist peptide by alanine scanning. 2012 Jan IL-15 is a proinflammatory cytokine that acts early in the inflammatory response and has been associated with several autoimmune diseases including rheumatoid arthritis, where it had been proposed as a therapeutic target. We recently reported an IL-15 antagonist peptide corresponding to sequence 36-45 of IL-15 (KVTAMKCFLL) named P8, which specifically binds to IL-15Rα and inhibits IL-15 biological activity with a half maximal inhibitory concentration (IC50) of 130 µ m in CTLL-2 proliferation assay. In order to improve binding of peptide P8 to the receptor IL-15Rα, we used an Ala scan strategy to study contribution of each individual amino acid to the peptide's antagonist effect. Here, we found that Phe and Cys are important for peptide binding to IL-15Rα. We also investigated other single site mutations and replaced the second Lys in the sequence by the polar non-charged amino acid threonine. The resulting peptide [K6T]P8 exhibited a higher activity than P8 with an IC50 of 24 µm. We also found that this peptide was more active than peptide P8 in the inhibition of TNFα secretion by synovial cells from rheumatoid arthritis patients. The peptide [K6T]P8 described in this work is a new type of IL-15 antagonist and constitutes a potential therapeutic agent for rheumatoid arthritis.
22972168 A study on the selection of DMARDs for the combination therapy with adalimumab. 2012 Jun 27 We evaluated whether or not the effect of adalimumab (ADA) in combination with the disease-modifying antirheumatic drugs (DMARDs) other than methotrexate (MTX) is comparable to the ADA+MTX therapy for the treatment of rheumatoid arthritis (RA). A total of 216 patients with active RA at Kohnan Kakogawa Hospital and Kobe University Hospital were enrolled. Clinical and functional outcomes were compared among 4 groups, ADA alone (A group), ADA + MTX (B group), ADA + MTX + other DMARDs (C group), and ADA + other DMARDs (D group), and the retention rates of ADA were evaluated with or without MTX. CRP was significantly decreased from initial measurement at 1 month in all 4 groups, but the continuous efficacy with the statistical significance at all measurement points were observed only in combination with MTX (P<0.05), which was reflected by significantly higher retention rates. Similarly, the disease activities were improved, and particularly the remission rates (DAS28-CRP < 2.3) of A, B and C groups (>42.9%) were higher than that of D group (29.4%) at 2 year. An index of patients' basic activities of daily living, M-HAQ score of A, B and C groups was also better than that of D group. While, looking at the mean changes of M-HAQ from the baseline at 2 years, potential effect of other DMARDs on M-HAQ was also suggested. The results show that ADA + MTX therapy is significantly superior than ADA + other DMARDs in ameliorating RA.
20974613 Inter-observer reliability of high-resolution ultrasonography in the assessment of bone er 2011 Feb OBJECTIVE: The present study was aimed at testing the ability of a rheumatologist without experience in ultrasound (US) who attended an intensive 4-week training programme focused on US assessing bone erosions in the hands and feet in patients with RA. METHODS: Twenty patients diagnosed with RA according to the ACR criteria were included in the study. All US examinations were performed bilaterally by two investigators (with different experience in the field of musculoskeletal US) at the following sites: the dorsal, lateral and volar aspect of the second metacarpal, ulnar and fifth metatarsal head; and the dorsal and volar aspect of the third metacarpal and second proximal heads. Each quadrant was scanning in longitudinal and transverse scans for assessing the qualitative, semiquantitative and quantitative US findings indicative of bone erosions according the OMERACT preliminary definition. RESULTS: Both κ-values and overall agreement percentages of qualitative and semiquantitative assessments showed moderate to excellent agreement between the two investigators. Similar results were obtained for the quantitative assessment with the concordance correlation coefficient value always significant. The only exception was the volar aspects, in particular those of the fifth metatarsal head. CONCLUSION: Our study suggests that after a 4-week dedicated training programme, a rheumatologist without experience in US is able to detect and score bone erosions in the hands and feet of patients with RA.
21586803 [Dissemination of medical knowledge to the public in Iceland by a country doctor 1782-1834 2011 May Jón Pétursson (1733-1801) was an apprentice af the first Chief Medical Officer of Iceland. In 1765 Pétursson enrolled in the Medical Faculty at the University of Copenhagen. In 1769 with the Faculties approval he published a monograph on the so called Icelandic Scurvy. In 1770-71 Pétursson served as ship's surgeon in the Royal Danish Navy on an expedition to the Mediterranean. In 1772-1775 he served as an assistant to the Chief Medical Officer and the newly appointed apothecary, who shared premises at Nes, Reykjavík. In 1775 he was appointed surgeon (chirurgeon) to the Northern District. Pétursson wrote two medical book while serving his district, both being prepared now for republication. A. The Lækningabók fyrir almúga (Leechbook for common people) published posthumously 1834, edited by Sveinn Pálsson surgeon. It was undoubtedly inspired by the Swiss physician Tissot and his book Avis au peuple sur sa santé ou traité des maladies plus fréquentes 1761. B. A treatise on rheumatism or dirorder of the joints (Stutt ágrip um iktsýki edur lidaveiki, 1782). In Scand J Rheumatol 1996: 25; 134-7 the authors point out that Péturssons description of what he calls arthritis vaga encompasses these essential features: It is common, chronic, destructive, inflammatory polyarthritis, sometimes with systemic manifestations. It affects peope of all ages and has a female preponderance. They state that only rheumatoid arthritis fulfills these specifications. They conclude that medical history should give Pétursson credit for the first definite description of rheumatoid arthritis.
23268368 The novel cytokine interleukin-36α is expressed in psoriatic and rheumatoid arthritis syn 2013 Sep 1 BACKGROUND: Interleukin (IL)-36α is a recently described member of the IL-1 cytokine family with pro-inflammatory and clearly pathogenic properties in psoriasis. OBJECTIVE: To determine the IL-36α expression in psoriatic arthritis (PsA) compared to rheumatoid arthritis (RA) and osteoarthritis (OA). METHODS: Synovial tissues obtained from arthritis patients were stained for IL-36α, IL-36 receptor (IL-36R) and IL-36R antagonist (IL-36Ra) by immunohistochemistry and immunofluorescence. Lysates were examined for IL-36α by western blot analysis. Synovial fibroblasts (FLS) cultured in the presence of IL-36α were assayed for cytokine expression by quantitative real time PCR and multiplex assay. IL-36α-induced signal transduction in FLS was analysed by immunoblotting. RESULTS: Expression of IL-36R and its ligands IL-36α and IL-36Ra was detected in the synovial lining layer and cellular infiltrates of patients with inflammatory arthritis. IL-36α was expressed significantly higher in PsA and RA than in OA synovium. CD138-positive plasma cells were identified as the main cellular source of IL-36α. No differences were observed for the expression of IL-36R and IL-36Ra between PsA, RA and OA. Functionally, IL-36α induced the expression of IL-6 and IL-8 in FLS through p38/NFkB activation. CONCLUSIONS: IL-36α is up-regulated in PsA and RA synovium, expressed by tissue plasma cells and leads to IL-6 and IL-8 production by synovial fibroblasts. Hence, IL-36α links plasma cells to inflammatory cytokine production by FLS and may represent a key link between autoimmunity and the induction of synovitis.
22393641 [Seroprevalence of HBsAgs in patients with rheumatoid arthiritis in a hospital setting in 2011 Dec PURPOSE: Rheumatoid arthritis is the most common chronic inflammatory joint disease in adults. In Senegal, where biotherapy is unavailable, treatment of RA relies on a combination of glucocorticoids and disease-modifying antirheumatic drugs (DMARD). Since DMARD, particularly methotrexate, induce hepatotoxicity pretreatment assays of serum transaminase and albumin levels, as well as serological tests for the hepatitis B and C viruses is recommended. Hepatitis B virus (HBV) infection is endemic in Africa, particularly in Senegal. The purpose of this study was to assess the seroprevalence of the HBV surface antigen (HBsAg) for HBV in 258 patients with RA in Senegal as a basis for defining the least hepatotoxic DMARD for these patients and ensuring the most suitable monitoring. METHOD: This retrospective study was based on a review of the medical records of patients examined between January 2005 and December 2009 at the rheumatology outpatient clinic of the Aristide Le Dantec Teaching Hospital in Dakar, Senegal. All patients met the American College of Rheumatology criteria for RA. RESULTS: A total of 258 patients were tested for HBsAg. Tests were positive in 6 for a seroprevalence of 2.3%. All 6 positive patients were women with a mean age of 48.7 years (range, 16-79 years). Transaminase levels were normal in 5 patients. In the remaining patient, ASAT level elevation were twice normal and ALAT was normal. No patients had clinical evidence of liver disease. CONCLUSION: HBsAg seroprevalence in our population of patients with RA was lower than in the general population of Senegal: 2.3% versus 15%-18%. No evidence indicated that HBVinfection produced specific features in patients with RA. Based on these findings, widespread use of methotrexate in optimal dosages appears safe in patients with RA in Senegal. Treatment should be accompanied by careful attention to HBV prevention.
21244218 Golimumab - a new tool in the armoury against inflammatory arthritis. 2011 Mar The development of biological drugs blocking tumour necrosis factor-alpha (TNF-α) has had a dramatic impact on the treatment of inflammatory arthritis in recent years. Golimumab is a fully human monoclonal antibody which inhibits TNF-α. It is licensed for the treatment of rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. In this review we evaluate the results of phase III studies using golimumab and explore the place of golimumab in the treatment of these diseases.
23039206 Serum IFN-λ1 is abnormally elevated in rheumatoid arthritis patients. 2013 Feb Interferon (IFN)-λ1 is a newly described cytokine that is known for its proinflammatory activity in viral infection and in cancer. Because recent studies indicated that IFN-λ can influence significantly the innate and adaptive immune response, we studied IFN-λ in a prototypic systemic autoimmune disease, rheumatoid arthritis (RA). It was found that RA patients had higher mRNA levels in PBMC and higher serum levels of IFN-λ1 in comparison with healthy matched controls and ankylosing spondylitis (AS) patients. Although there was no correlation between serum IFN-λ1 and RA autoantibodies, RA patients that presented knee joint involvement displayed higher serum IFN-λ1 than patients without knee joint involvement, suggesting that abnormally elevated IFN-λ1 levels in RA can associate with knee joint disease.
23137648 The low binding affinity of ADAMTS4 for citrullinated fibronectin may contribute to the de 2013 Mar OBJECTIVES: Rapid cartilage degradation in the joints is observed in rheumatoid arthritis (RA). ADAMTS4 (a disintegrin and metalloproteinase with thrombospondin motifs-4) degrades aggrecan, the primary component of cartilage, therefore contributing to joint erosion in RA. The proteolytic activity of ADAMTS4 is inhibited by fibronectin (FN). FN is abundantly expressed in the synovia in RA and is modified by citrullination, the conversion of peptidylarginine to citrulline. This study aims to investigate the binding ability of citrullinated FN (cFN) to ADAMTS4 and the effect of cFN on aggrecanase activity. METHODS: The full-length recombinant ADAMTS4 was purified from HEK293 cells that were transiently transfected with a full-length cDNA coding for human ADAMTS4. A 40-kDa FN fragment exhibiting heparin binding was citrullinised with rabbit peptidylarginine deaminase. The binding activity of the full-length recombinant ADAMTS4 to cFN was investigated in an in vitro binding assay. The proteolytic activity of ADAMTS4 after incubation with cFN was determined using an aggrecanase activity kit, in which the ARGSVIL peptide is produced by digestion with aggrecanase. RESULTS: cFN displayed significantly decreased binding activity with ADAMTS4 compared with FN. The full-length ADAMTS4 produced large amounts of the ARGSVIL peptide, but the amount was markedly decreased in the presence of FN. The production of this peptide approached the normal level when the full-length ADAMTS4 was incubated with cFN. CONCLUSIONS: FN following citrullination is less effective in inhibiting the proteolytic activity of ADAMTS4. It is known that PADI4, an enzyme active in citrullination, is highly expressed in the synovial tissue in RA. Our results suggest that PADI4 in the RA synovium may contribute to cartilage destruction via the citrullination of FN.
20721560 Synovial fluid adenosine deaminase and high-sensitivity C-reactive protein activity in dif 2012 Jan It is proposed that synovial fluid biomarkers may help in differentiating the type of arthritis. The aim of study is to determine whether synovial fluid adenosine deaminase (ADA) and high-sensitivity C-reactive protein (hs-CRP) can be useful in this regard. A total of 75 patients with knee monoarthritis that were admitted in Shahid Beheshti Kashan hospital in 2009 included in the study. There were 18 rheumatoid arthritis, 13 crystal-induced arthritis, 3 septic arthritis and 41 osteoarthritis. Inflammatory arthritis was diagnosed if more than 2,000 white blood cells existed in per milliliter of the synovial fluid. There was statistically significant difference in mean synovial fluid ADA and hs-CRP concentration between inflammatory (26.06 ± 8.96 IU/l, 12.72 ± 9.25 μg/ml) and non-inflammatory arthritis (14.8 ± 2.79 IU/l, 2.36 ± 2.7 μg/ml) (P values = 0.00, 0.00). There was statistically significant difference in mean synovial fluid ADA and hs-CRP concentration when rheumatoid arthritis (23.77 ± 4.58 IU/l, 10.47 ± 6.99 μg/ml), crystal-induced arthritis (22.76 ± 3.65 IU/l, 14.37 ± 11.58 μg/ml) and septic arthritis (49.66 ± 8.96 IU/l, 18.25 ± 5.37 μg/ml) were compared with osteoarthritis (14.58 ± 2.63 IU/l, 1.91 ± 1.31 μg/ml) (All P values = 0.00). There was statistically significant difference in mean synovial fluid ADA concentration between septic and rheumatoid arthritis and also between septic arthritis and crystal-induced arthritis (P values = 0.00, 0.00). This study showed that synovial fluid ADA and hs-CRP can properly differentiate inflammatory from non-inflammatory arthritis. Synovial fluid ADA is a useful marker in differentiating septic from rheumatoid and crystal-induced arthritis.
22128080 Antibodies against cyclic citrullinated peptides of IgG, IgA and IgM isotype and rheumatoi 2012 Jun BACKGROUND: Rheumatoid factors (RFs) and antibodies against cyclic citrullinated peptides (CCPs) of IgG, IgA and IgM isotype have been shown to precede disease onset by years. OBJECTIVE: To evaluate serological risk markers in first-degree relatives from multicase families in relation to genetic and environmental risk factors. METHODS: 51 multicase families consisting of 163 individuals with rheumatoid arthritis (RA) (mean±SD age, 60±14 years; disease duration 21 years; 71.8% female) and with 157 first-degree relatives unaffected by RA (54±17 years; 59.9% female) were recruited. Isotypes of antibodies against CCPs (IgG, IgA and IgM) and RFs (IgM and IgA) were determined using automated enzyme immunoassays. Cut-off levels were established using receiver operating characteristic curves based on values for 100 unrelated healthy controls. RESULTS: The concentrations and frequencies of all anti-CCP and RF isotypes were significantly increased in first-degree relatives and patients with RA compared with unrelated healthy controls. The relative distribution of IgA and IgM isotypes was higher than IgG in the relatives, whereas the IgG isotype dominated in patients with RA. The patients carried human leucocyte antigen-shared epitope (HLA-SE) significantly more often than the relatives (71.4% vs 53.9%, p=0.01), while the frequency of the PTPN22 T variant was similar. HLA-SE, combined with smoking, was significantly related to all combinations of anti-CCP and RF isotypes in patients with RA. No such relationships were found for the first-degree relatives. CONCLUSIONS: All anti-CCP and RF isotypes analysed occurred more commonly in unaffected first-degree relatives from multicase families than in controls, but with different isotype distribution from patients with RA.
22920577 In vitro glucocorticoid sensitivity is associated with clinical glucocorticoid therapy out 2012 Aug 24 INTRODUCTION: Genetic and disease-related factors give rise to a wide spectrum of glucocorticoid (GC) sensitivity in rheumatoid arthritis (RA). In clinical practice, GC treatment is not adapted to these differences in GC sensitivity. In vitro assessment of GC sensitivity before the start of therapy could allow more individualized GC therapy. The aim of the study was to investigate the association between in vitro and in vivo GC sensitivity in RA. METHODS: Thirty-eight early and 37 established RA patients were prospectively studied. In vitro GC sensitivity was assessed with dexamethasone-induced effects on interleukin-2 (IL-2) and glucocorticoid-induced leucine zipper (GILZ) messenger RNA expression in peripheral blood mononuclear cells (PBMCs). A whole-cell dexamethasone-binding assay was used to measure number and affinity (1/KD) of glucocorticoid receptors (GRs). RESULTS: GR number was positively correlated with improvement in DAS. IL-2-ECâ‚…â‚€ and GILZ-ECâ‚…â‚€ values both had weak near-significant correlations with clinical improvement in DAS in intramuscularly treated patients only. HAQ responders had lower GILZ-ECâ‚…â‚€ values and higher GR number and KD. CONCLUSIONS: Baseline cellular in vitro glucocorticoid sensitivity is modestly associated with in vivo improvement in DAS and HAQ-DI score after GC bridging therapy in RA. Further studies are needed to evaluate whether in vitro GC sensitivity may support the development of tailor-made GC therapy in RA.