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ID PMID Title PublicationDate abstract
22039170 Interleukin 34 expression is associated with synovitis severity in rheumatoid arthritis pa 2012 Jan OBJECTIVES: Interleukin (IL) 34 is a new cytokine implicated in macrophage differentiation and osteoclastogenesis. This study assessed IL-34 expression in the tissue of patients with rheumatoid arthritis (RA). METHODS: Immunohistochemistry was performed in synovial biopsies from patients with RA (n=20), osteoarthritis (n=3) or other inflammatory arthritis (n=4). IL-34 was detected in the synovial fluid by ELISA and its messenger RNA expression was studied by quantitative PCR in rheumatoid synovial fibroblasts after stimulation by tumour necrosis factor α (TNFα) and IL-1β. Wild-type, jnk1(-/-)-jnk2(-/-) and nemo(-/-) murine fibroblasts and pharmacological inhibition were used to determine the involvement of nuclear factor kappa B (NF-κB) and JNK in that effect. RESULTS: IL-34 was expressed in 24/27 biopsies, with three samples from RA patients being negative. A significant association was found between IL-34 expression and synovitis severity. Levels of IL-34 and the total leucocyte count in synovial fluid were correlated. TNFα and IL-1β stimulated IL-34 expression by synovial fibroblasts in a dose/time-dependent manner through the NF-κB and JNK pathway. CONCLUSION: This work for the first time identifies IL-34 expression in the synovial tissue of patients with arthritis. This cytokine, as a downstream effector of TNFα and IL-1β, may contribute to inflammation and bone erosions in RA.
23178207 Cardiovascular comorbidities antedating the diagnosis of rheumatoid arthritis. 2013 Nov OBJECTIVES: To assess the prevalence of coronary heart disease (CHD) and chronic hypertension among patients with rheumatoid arthritis (RA) at the time of diagnosis, in comparison with age-specific and sex-specific non-RA subjects. Furthermore, the impacts of age at the onset of RA, as well as gender and the presence of rheumatoid factor (RF) on the risk of these comorbidities, were evaluated. METHODS: A cohort of 7209 RA patients diagnosed between January 2004 and December 2007 was identified, based on a Finnish nationwide register on special reimbursements for medication costs. The presence of CHD and chronic hypertension antedating the diagnosis of RA was identified from the same register. The prevalence of the cardiovascular comorbidities was compared with the general Finnish population, and a standardised rate ratio (SRR) for both these cardiovascular diseases was calculated. RESULTS: The risk of having CHD at RA diagnosis was slightly elevated, the SRR being 1.10 (95% CI 1.01 to 1.20). Younger age at the onset of RA seemed to be related with higher SRR for CHD. In a subset analysis, an increased prevalence of hypertension (SRR 1.19, 95% CI 1.10 to 1.30) and CHD (SRR 1.15, 95% CI 1.00 to 1.32) was apparent only among the RF negative RA cases. CONCLUSIONS: The SRR for CHD is augmented in RA patients already at disease onset, and more pronouncedly in early onset RA. The findings highlight the importance of early prevention of atherosclerosis, regardless of RF status.
20965550 Posterior interosseous nerve palsy: an unusual complication of rheumatoid arthritis: case 2011 Jun OBJECTIVES: Posterior interosseous nerve (PIN) palsy is a very rare complication of rheumatoid arthritis affecting the elbow joint. It results in weakness of extension of the fingers and may be confused with extensor tendon rupture and wrist drop due to radial nerve damage. METHODS: We present a case of PIN palsy secondary to rheumatoid synovitis and review the previously reported cases. RESULTS: Eighteen cases of PIN palsy due to rheumatoid arthritis have been reported so far in the literature. CONCLUSIONS: It is important to recognize this complication and early intervention is necessary to prevent permanent damage.
23044162 Nutritional status in relation to adipokines and oxidative stress is associated with disea 2012 Nov OBJECTIVE: We assessed whether disease activity was associated with dietary habits, nutritional status, adipokines, and oxidative stress in patients with rheumatoid arthritis. METHODS: The subjects were 37 patients with RA. The assessment of the nutritional status included anthropometric and biochemical parameters. A food-frequency questionnaire and a 3-d diet record to assess dietary intake were used. The serum levels of adipokines and oxidative stress markers in sera and saliva were measured. The disease activity was determined using the 28 Disease Activity Score (DAS28). We divided the subjects into high (DAS28 ≥3.2) and low (DAS28 <3.2) disease activity groups. RESULTS: The serum leptin and albumin levels were significantly lower, whereas the inflammatory markers were increased, in the high disease activity group. The dietary intake assessment showed a lower intake of fish oil and a lower ratio of monounsaturated fatty acid intake in the high disease activity group. There was a negative correlation between the DAS28 and the dietary intake of the ratio of monounsaturated fatty acid to total fatty acid intake. The serum oxidative stress marker (reactive oxygen metabolites) showed a positive correlation to the DAS28. The salivary reactive oxygen metabolites also correlated with C-reactive protein and serum reactive oxygen metabolites. CONCLUSION: Altered serum adipokine levels with decreased albumin may reflect the deterioration that is associated with rheumatoid arthritis. An increased oxidative stress was observed in sera and saliva. Intakes of ω-3 polyunsaturated fatty acids, fish oil, and monounsaturated fatty acid seem to affect disease activity and may have beneficial effects by decreasing inflammation.
21752868 PTPN22 R620W genotype-phenotype correlation analysis and gene-environment interaction stud 2011 Oct OBJECTIVES: To investigate genotype-phenotype correlation and gene-environment interaction between PTPN22 R620W environmental factors such as tobacco/hormonal treatments in an inception cohort of RA patients. METHODS: An intra-cohort study including 532 Caucasian RA patients genotyped for the PTPN22 rs2476601 polymorphism was performed. Anti-CCP and RF status at baseline, presence of bone erosions at 1 year, HLADR1 and/or DR4 status, demography, comorbidities, exposure to tobacco with the cumulative dose in pack-years, hormonal treatments and treatments received for RA were collected. Logistic regression was performed to estimate the ORs and multiplicative interaction with adjustment for confounding factors. Gene-environment interaction was estimated by the relative excess risk due to interaction (RERI), attributable proportion (AP) and synergy index (SI). RESULTS: PTPN22 620W risk allele was associated with ACPA production [odds ratio (OR) = 2.21, 95% CI 1.4, 3.4, P < 0.0001]. Hormonal treatment exposition and smoking were found to act with a protective effect against ACPA production (OR = 0.44, 95% CI 0.3, 0.7, P = 0.001) and early bone erosion (OR = 0.56, 95% CI 0.4-0.8, P = 0.003), respectively, and independently of HLADR and PTPN22 status. No evidence for a gene-environment interaction was detected. CONCLUSION: These data provide new insights into the pathogenesis of RA, underlying the pivotal key role of environmental factors in the typical heterogeneity of RA.
22128075 Misclassification of disease activity when assessing individual patients with early rheuma 2012 Jun OBJECTIVE: To study whether assessment of rheumatoid arthritis (RA) disease activity in individual patients using the disease activity score in 28 joints (DAS28) or other instruments excluding joints of feet may lead to misclassification of disease activity. METHODS: A cohort of RA patients was classified into three 'regional radiographic damage progression' groups: predominantly progression in feet, similar progression in hands and feet and predominantly progression in hands; both in early (0-2 years) and later (2-5 years) disease. Baseline and mean DAS28, individual DAS28 variables and tender joint counts (TJC) and swollen joint counts (SJC) of the feet were compared between groups. The longitudinal relation of DAS28 with radiographic damage was investigated using a mixed model analysis with rheumatoid factor status, baseline joint damage and TJC and SJC of the feet as covariates. RESULTS: Early (n=265) and later (n=200) in the disease course, by definition, the classification procedure resulted in 25% as predominantly foot, 25% as predominantly hand and 50% as similar progressors. In early RA predominantly foot progressors had higher TJC and SJC of the feet compared with predominantly hand progressors (p<0.001), but DAS28 was similar. This was not seen in later disease. The longitudinal relation between DAS28 and radiographic progression was influenced by the region of progression (predominantly foot progressors vs others, p<0.001), suggesting that DAS28 underestimates disease activity in predominantly foot progressors. In this group, joint counts for the feet were independently related to radiographic progression. CONCLUSIONS: DAS28 underestimates actual disease activity and expected joint damage of individual early RA patients predominantly with disease in the feet.
22749779 The presence of anti-LPS antibodies and human serum activity against Proteus mirabilis S/R 2012 Nov OBJECTIVES: Proteus mirabilis strains are human pathogens responsible for urinary tract infections, which may also be involved in rheumatoid arthritis (RA). DESIGN AND METHODS: We determined whether the binding site of anti-LPS antibodies on the O-polysaccharide part of P. mirabilis LPS correlates with the level of TLR4 (Thr399Ile) gene polymorphism in the sera of RA patients. We investigated the deposition of C3d and C5b complement components on the P. mirabilis LPS. The ELISA method used in this study was optimized with LAL test and laser interferometry. RESULTS: Depending on LPS P. mirabilis used in these studies, the amount of antibodies in RA patients sera varied. We did not observe a correlation between anti-LPS antibodies binding and the level of TLR4 (Thr399Ile) gene polymorphism. We found that the lower complement components deposition by O49 in contrast to O9 LPS correlates with its reduced sensitivities to human complement-mediated killing. CONCLUSION: The immunological response against P. mirabilis LPS might play a role in rheumatoid arthritis.
21933115 Prostaglandin E2 binding peptide: a potential modulatory agent which acts through suppress 2012 Feb In an earlier study, we found PBP inhibited the progress of adjuvant-induced arthritis (AA). This study was aimed at evaluating the inhibitory effects of PBP in terms of NF-κB activation by using immunohistochemical and immunofluorescent technique in vitro and in vivo. IL-1β and TNF-α in serum were detected by method of ELISA. Immunofluorescent results showed that PBP inhibited NF-κB p65 translocation into nucleus. In vivo imaging showed that treatment with PBP decreased the enzyme labeling signal of NF-κB p65. Immunohistochemical staining revealed that PBP suppressed production of NF-κB p65 subunit in the joints and attenuated the productions of IL-1β and TNF-α in serum from AA. Moreover, NF-κB p65 nucleus translocation was prevented by simultaneous incubation with PBP and PGE2 was decreased by PBP through a feedback cycle. We report the first confirmation of the mimotope of PGE2 receptor EP4 modulatory action.
22449071 Tec family kinases in inflammation and disease. 2012 Apr Over the last decade, the Tec family of nonreceptor tyrosine kinases (Btk, Tec, Bmx, Itk, and Rlk) have been shown to play a key role in inflammation and bone destruction. Bruton's tyrosine kinase (Btk) has been the most widely studied due to the critical role of this kinase in B-cell development and recent evidence showing that blocking Btk signaling is effective in ameliorating lymphoma progression and experimental arthritis. This review will examine the role of TFK in myeloid cell function and the potential of targeting these kinases as a therapeutic intervention in autoimmune disorders such as rheumatoid arthritis.
22607178 Tofacitinib for the treatment of rheumatoid arthritis. 2012 May Rheumatoid arthritis (RA) is a chronic inflammatory disease that affects approximately 1% of the worldwide population. It primarily targets the synovial membrane of joints, leading to a synovial proliferation, joint cartilage lesion and erosions in the adjacent bone tissue. The disease is usually progressive and if the inflammatory process is not adequately suppressed, joint deformity takes place, leading to a significant functional disability and work incapacity. Over the last decade, biological therapy was established as a major step towards disease control in those patients who experienced failure after treatment with disease-modifying antirheumatic drugs. Despite the growing number of biological agents with different immunological targets, a significant number of patients do not receive appropriate disease control, or have the use of these agents limited because of adverse events. As such, the search for new molecules with a higher efficacy and better safety profile is ongoing. This article focuses on a new drug, tofacitinib, which is a synthetic disease-modifying antirheumatic drug for treatment of RA. Preclinical studies in arthritis and transplantation animal models are reviewed as a background for the possible use of tofacitinib treatment in humans. Four Phase II (one A and three B dose-ranging) trials lasting from 6 to 24 weeks in RA patients showed significant American College of Rheumatology 20 improvements as early as week 2 and sustained at week 24 in two studies. Tofacitinib Phase III studies in RA are included in a clinical program called 'ORAL Trials'. Long-term follow-up from ongoing studies will contribute to a more accurate tofacitinib efficacy and safety profile. Trials in other illness such as psoriasis, psoriatic arthritis, renal transplant rejection prevention, inflammatory bowel diseases and dry eye are underway.
22211358 Functional folate receptor beta-expressing macrophages in osteoarthritis synovium and thei 2012 Mar OBJECTIVE: The distribution of folate receptor (FR)-β+ macrophages and their M1/M2 expression profiles were examined in osteoarthritis (OA) synovial tissues, and compared to those in rheumatoid arthritis (RA) synovial tissues and CD163+ macrophages in both OA and RA synovial tissues. METHOD: The phenotypes and fluorescein isothiocyanate (FITC)-folate uptake of FR-β+ synovial macrophages were analysed by flow cytometry. The distribution of FR-β+ macrophages in OA and RA synovial tissues was examined by immunofluorescent microscopy. Tumour necrosis factor (TNF)-α, inducible nitric oxide synthase (iNOS), interleukin (IL)-10, and transforming growth factor (TGF)-β expression in FR-β+ macrophages was detected by double-immunostaining in both OA and RA synovial tissues. RESULTS: FR-β+ macrophages were predominantly present in the synovial lining layer in OA patients. The proportion of CD163-FR-β+ cells in synovial mononuclear cells (MNCs) was increased in OA compared to RA synovial tissues. FR-β(high) macrophages from OA synovial tissues represented the majority of folic acid-binding cells. Although FR-β+ or CD163+ macrophages in the synovial tissues of OA and RA patients expressed a mixed pattern of M1 and M2 macrophage markers, there were more M2 markers expressing synovial macrophages in OA than in RA patients. CONCLUSIONS: The distribution and M1/M2 expression profiles of FR-β+ synovial macrophages were different between OA and RA synovial tissues. Thus, the findings underscore that the M1/M2 paradigm using surface markers FR-β and CD163 is an oversimplification of macrophage subsets. Functional FR-β present on OA synovial macrophages provides a potential tool for the diagnosis and treatment of OA.
21391902 Chronic inflammatory disorders and their redox control: from molecular mechanisms to thera 2011 Nov 1 A chronic inflammatory disease is a condition characterized by persistent inflammation. A number of human pathologies fall into this category, and a great deal of research has been conducted to learn more about their characteristics and underlying mechanisms. In many cases, a genetic component has been identified, but also external factors like food, smoke, or environmental pollutants can significantly contribute to worsen their symptoms. Accumulated evidence clearly shows that chronic inflammatory diseases are subjected to a redox control. Here, we shall review the identity, source, regulation, and biological activity of redox molecules, to put in a better perspective their key-role in cancer, diabetes, cardiovascular diseases, atherosclerosis, chronic obstructive pulmonary diseases, and inflammatory bowel diseases. In addition, the impact of redox species on autoimmune disorders (rheumatoid arthritis, systemic lupus erythematosus, psoriasis, and celiac disease) and neurodegenerative diseases (Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis) will be discussed, along with their potential therapeutic implications as novel drugs to combat chronic inflammatory disorders.
21318306 Prosthetic joint infection after total hip or knee arthroplasty in rheumatoid arthritis pa 2011 Oct The aim of this study was to identify risk factors for acute surgical-site infection (SSI) after total joint arthroplasty in rheumatoid arthritis (RA) patients treated with nonbiologic and biologic disease-modifying antirheumatic drugs (DMARDs). We performed a retrospective study of all consecutive total hip (THA) and total knee (TKA) arthroplasties performed during a 5-year period (THA 81; TKA 339). Multivariate logistic regression analysis was performed to identify SSI risk factors. Of the patients undergoing THA or TKA, 24 cases (5.7%) developed a superficial incisional SSI requiring the use of antibiotics and three cases (0.7%) developed an organ/space SSI necessitating surgical treatment to remove the artificial joint prosthesis. Multivariate logistic regression analysis revealed that the use of biologic DMARDs [P = 0.0007, odds ratio (OR) = 5.69; 95% confidence interval (CI) 2.07-15.61] and longer RA duration (P = 0.0003, OR = 1.09; 95% CI 1.04-1.14) were the only significant risk factors for acute SSI. Furthermore, an analysis that individually evaluated major agents (n > 10) adjusted for disease duration indicated that tumor necrosis factor alpha blockers increased the risk of SSI (infliximab P = 0.001, OR = 9.80, 95% CI 2.41-39.82; etanercept P = 0.0003, OR = 9.16, 95% CI 2.77-30.25). We found that the use of infliximab or etanercept and longer disease duration were associated with an increased risk of acute SSI in RA patients. Prospective studies are thus needed to determine the safety of biologic DMARDs in the perioperative period.
22350572 Tumor necrosis factor-alpha antagonist therapy-induced psoriasis in Turkey: analysis of 51 2012 Sep OBJECTIVES: New adverse events are being reported with the increased use of anti-tumor necrosis factor (TNF) α therapy. We studied cases of anti-TNFα-induced psoriasis observed in our pool of 514 patients receiving anti-TNFα treatment in Turkey. METHODS: Three rheumatoid arthritis patients and 3 ankylosing spondylitis patients with anti-TNFα-induced psoriasis were included in the study. All patients were examined by a dermatologist, and 3 patients underwent skin biopsy. RESULTS: None of the 6 patients had preexisting psoriasis or a familial history of psoriasis. The earliest and latest occurrences of psoriatic lesions were at the 6th week and 44th month of anti-TNFα therapy, respectively. Psoriasis was severe and refractory in two patients (requiring systemic treatment), while it presented as mild in four patients. Anti-TNFα therapy was totally withdrawn in case 1. In case 2, the treatment was halted for 3 months then switched to another TNFα blocker, and case 3 was switched to another anti-TNFα treatment. The treatment was sustained in the other 3 patients (cases 4, 5, and 6). CONCLUSIONS: TNFα blockers are very effective agents in the treatment of psoriasis, but it is interesting that the same molecules can, paradoxically, induce psoriasis. The occurrence of anti-TNFα-induced psoriasis in six out of 514 patients suggests that the incidence of this adverse reaction is, in fact, as not low as presumed in the literature. In some cases, a severe course of psoriasis may limit the use of these agents.
22933683 Arthroscopic synovectomy for rheumatoid wrists and elbows. 2012 Aug PURPOSE: To evaluate the treatment outcome of wrist and elbow arthroscopic synovectomy for patients with rheumatoid arthritis. METHODS: 3 men and 18 women aged 27 to 71 (mean, 54) years underwent arthroscopic synovectomy for rheumatoid arthritis of the wrist (n=12) and elbow (n=13). All patients had received multiple medications including non-steroidal anti-inflammatory drugs, disease-modifying anti-rheumatic drugs, and steroids, as well as physiotherapy and splintage for 6 months, but the joint pain and disability persisted. The median duration of rheumatoid arthritis was 89 (range, 24-156) and 108 (range, 36-360) months for the wrist and elbow joints, respectively. According to the Larsen grading, the radiographic stages of the wrists and elbows were classified as grade 1 (n=4+4), grade 2 (n=4+5), and grade 3 (n=4+4). Visual analogue scale for pain, the wrist and elbow flexion-extension arcs, grip strength, key pinch strength, inflammatory markers, disability and symptoms were compared pre- and post-operatively. RESULTS: The median follow-up period was 30 (range, 18-78) and 34 (range, 18-78) months for wrists and elbows, respectively. There was significant improvement in pain, joint motion, inflammatory markers, and disability score. All patients were satisfied with the surgery. There was no neurovascular or wound complication. No patient was taking longterm pain-control drugs. One patient underwent a second arthroscopic synovectomy after 15 months owing to exacerbation of arthritis. CONCLUSION: Arthroscopic synovectomy is recommended for patients with rheumatoid arthritis who fail conservative treatment.
21572145 Cartilage oligomeric matrix protein associates differentially with erosions and synovitis 2011 Aug OBJECTIVE: Cyclic citrullinated peptide antibody (anti-CCP)-positive and anti-CCP-negative rheumatoid arthritis (RA) have been suggested as 2 distinctive disease subsets with respect to disease activity and prognosis. Previously, we proposed that anti-CCP antibodies might have a chondrocyte-suppressive effect. We aimed to compare circulating cartilage oligomeric matrix protein (COMP), a marker of cartilage turnover, in untreated anti-CCP-positive and anti-CCP-negative RA, and to study the temporal pattern of COMP through 4 years of treatment, including the relationship to imaging and clinical findings. METHODS: A total of 160 patients with newly diagnosed RA who were naive to disease-modifying antirheumatic drugs were included in the CIMESTRA trial. Ninety healthy blood donors served as controls. Demographic and disease measures including Disease Activity Score in 28 joints, IgM rheumatoid factor, anti-CCP, Health Assessment Questionnaire, visual analog scale scores for pain and global and physician assessment, and magnetic resonance imaging (MRI) of the nondominant hand were recorded at baseline. COMP in serum was measured by ELISA at inclusion and serially through 4 years. RESULTS: Median baseline COMP was higher in patients with RA [9.8 U/l (interquartile range 8.96, 10.5)] compared with controls [8.3 U/l (IQR 7.84, 8.9); p < 0.001] and remained elevated at 4 years [10.8 U/l (IQR 10.2, 11.7); p < 0.001]. At baseline, anti-CCP-positive patients had lower COMP than anti-CCP-negative patients (p = 0.048). In anti-CCP-positive patients, COMP exhibited a parabolic course over 4 years, while COMP in anti-CCP-negative patients had an almost linear course. In anti-CCP-positive patients, COMP was associated with MRI edema and erosion score, while COMP was correlated with synovitis score in anti-CCP-negative individuals. CONCLUSION: Our study provides additional evidence for the existence of different disease pathways in anti-CCP-positive and anti-CCP-negative subsets of RA, and evidence that anti-CCP antibodies may be implicated in the disease process by modifying cartilage metabolism.
21965646 Safety and effectiveness of rituximab in patients with rheumatoid arthritis following an i 2011 Dec OBJECTIVE: To evaluate the safety and effectiveness of rituximab (RTX) in combination with methotrexate in patients with active rheumatoid arthritis (RA) after failure of a single tumor necrosis factor-α (TNF-α) inhibitor. Changes in patient-reported outcomes after primary treatment or retreatment with RTX and factors determining retreatment in clinical practice were also evaluated. METHODS: In this phase 3b open-label, multicenter trial, patients received 2 slow infusions of RTX 1000 mg 14 days apart after premedication (primary treatment). Patients with a clinically relevant response could receive retreatment between 24 and 48 weeks. The primary endpoint was evaluation of safety. Secondary outcomes were safety of retreatment, effectiveness of primary treatment and retreatment, and changes in patient-reported outcomes after primary treatment or retreatment. RESULTS: Of 120 patients enrolled at 36 centers and receiving primary RTX treatment, 77 received retreatment, 112 completed the 24-week primary treatment period, and 25 completed the 48-week primary treatment and retreatment period following a single course of RTX. The most common adverse events were mild to moderate nausea, vomiting, nasopharyngitis, and headache. No infections or infusion reactions were considered life-threatening. At 24 weeks, 58%, 27%, and 7% of patients achieved American College of Rheumatology 20, 50, and 70 improvements, respectively, and similar improvements were seen after retreatment. CONCLUSION: RTX was well tolerated, with a low incidence of infusion reactions and infections. Efficacy results, including enhanced response in rheumatoid factor-positive patients, were comparable to those reported in the literature. Based on its efficacy and safety profile and retreatment schedule, RTX is an attractive treatment option for patients that have not responded to a single TNF-α inhibitor.
23298497 Immunogenetics and HPLC analyses contribute to understanding the etiopathology of rheumato 2012 Oct Genetic investigations on ancient human remains affected by rheumatological pathologies are a research field of particular interest for identifying origins and the etiopathology of diseases, especially those having an autoimmune background such as rheumatoid arthritis (RA). We wish to demonstrate how reliable studies concerning this topic require collaboration between multiple disciplines, usually starting from paleopathologic observations up to immunogenetic screening, even involving analytical chemistry. Here, we focused our investigation on the skeleton of Cardinal Carlo de'Medici (1595-1666) for whom RA and psoriatic arthritis (PsA) were postulated after paleopathologic examination. RA susceptibility is linked to specific HLA alleles belonging to DRB1 04 locus, such as DRB1 0401, while Cw 0602 and DRB1 07 predispose to PsA. Thus, we genotyped the Cardinal?s remains to search for RA or PsA risk genes. Ancient DNA is often subjected to hydrolysis followed by fragmentation. For this reason, all immunogenetic tests were preceded by an original RP-HPLC-FL method able to inform on the ancient DNA preservation and the extent of contamination, with the purpose of avoiding the risk of false positive results. After DNA isolation from a piece of bone from the Cardinal, PCR-SSP and reverse-SSO hybridization assays were applied to perform genomic HLA-typing. RP-HPLC-FL analysis revealed a good preservation of DNA without contamination by exogenous genomes. Molecular tests assigned to the Cardinal the genotype DRB1 0401/1102 for HLA-DRB locus and Cw 04/ 12 for HLA-C locus, data that support a genetic predisposition for RA but not for PsA. This multidisciplinary study has allowed us: (i) to ascertain that the remains undoubtedly belonged to the specific subject, Cardinal Carlo de?Medici; (ii) to sustain that the subject suffered from RA rather then that PsA, and (iii) to state that RA was already widespread in Europe at the Renaissance age, despite some authors claiming that the disease was introduced to the Old Continent from America after colonization during the 18th century.
21713412 Antibodies to citrullinated protein antigens (ACPAs): clinical and pathophysiologic signif 2011 Oct Antibodies to citrullinated protein antigens (ACPAs) are highly specific for rheumatoid arthritis (RA) and are useful in the diagnosis of RA as well as the prediction of the course and outcomes of disease. Multiple methodologies exist for measuring ACPAs, including the widely available tests for anticyclic citrullinated peptide antibodies and for antibodies to mutated/modified citrullinated vimentin. These methodologies overall have similar diagnostic accuracies for RA, although there is some variability. The discovery of ACPAs and the biology of citrullination have also led to important advances in the understanding of the pathophysiology and development of RA, especially regarding the relationship between potential genetic and environmental risk factors for RA. Going forward, research into autoimmunity to citrullinated proteins may help identify the specific etiology of RA and provide approaches for the prediction of future risk of disease, and ultimately prevention of RA.
21609481 Cross-cultural validation of the Educational Needs Assessment Tool in RA in 7 European cou 2011 May 24 BACKGROUND: The Educational Needs Assessment Tool (the ENAT) is a 39-item patient questionnaire originally developed in the UK to assess educational needs of patients with rheumatoid arthritis (RA). The objective of this study was to assess the cross-cultural validity of the ENAT in 7 European countries. METHODS: The ENAT was translated into Dutch, Finnish, Norwegian, Portuguese, Spanish and Swedish versions by using Beaton's cross-cultural adaptation process, and was completed by a convenience sample of patients with RA in each country. The generated country-specific data were assessed for construct validity and were then pooled and assessed for cross-cultural invariance using Rasch analysis. RESULTS: Individual country-specific analysis showed adequate fit to the Rasch model after adjustment for local dependency within domains. When data from the different countries were pooled, the 39 items deviated significantly from Rasch model's expectations (X(2)=977.055, DF=351, p=0.000, PSI=0.976). Again, most items within domains were found to be locally dependent, significantly affecting the fit. Consequently each domain was treated as a unit (i.e. testlet) and the ENAT was re-analysed as a seven-testlet scale resulting into a good fit to the Rasch model (X(2)=71.909; DF=63; p=0.207, PSI=0.951). A test of strict unidimensionality confirmed that all domains contributed to measuring a single construct. Cross-cultural non-invariance was discounted by splitting domains for DIF maintaining an excellent fit to the Rasch model. This allowed calibration of the ENAT into an interval scale. CONCLUSION: The ENAT is a simple tool, which is a valid measure of educational needs of people with RA. Adjustment for cross-cultural non-invariance is available if data from the 7 European countries are to be pooled or compared.