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ID PMID Title PublicationDate abstract
16739186 Rheumatology care: Involvement in medical decisions, received information, satisfaction wi 2006 Jun 15 OBJECTIVE: To examine levels of received information, involvement in medical decisions, and satisfaction with care, to explore factors related to current involvement in medical decisions, and to assess patients' unmet health care needs related to their disease. METHODS: A total of 1,193 patients with rheumatoid arthritis and ankylosing spondylitis completed self-reported health status questionnaires, including registration of sociodemographic data and questions about rheumatology care. Separate questions addressed information received, involvement in decisions, and satisfaction with care. Aspects of unmet health were assessed by an open-ended question. RESULTS: The majority of patients reported medium to high levels of received information, involvement in medical decisions, and satisfaction with care. High involvement in medical decisions was univariately associated with high levels of perceived information and satisfaction, as well as with lower age and a good health status. In the multivariate analyses, patient satisfaction (odds ratio [OR] 4.21) and a high level of received information (OR 7.85), age (OR 0.99), and >12 years of formal education (OR 1.46) remained as significant predictors to current involvement. Nearly one-third reported a variety of unmet health care needs, and this report was associated with poor health. CONCLUSION: The results indicate a need for a more flexible and patient centered care model, in which patients to a larger degree can decide which services they need and how these services should be delivered.
16385495 The effectiveness of anti-tumor necrosis factor therapy in preventing progressive radiogra 2006 Jan OBJECTIVE: To compare the effectiveness of 3 therapeutic strategies in preventing progressive joint damage, in a population-based cohort. The 3 strategies were infliximab with concomitant disease-modifying antirheumatic drugs (DMARDs), etanercept with concomitant DMARDs, and etanercept alone. METHODS: We used sequential radiographs to assess all patients who were treated with infliximab or etanercept for >10 months. The rates of erosion progression and joint space narrowing (JSN) were analyzed using multivariate regression models for longitudinal data, with adjustment for potential confounders. RESULTS: A total of 372 patients treated with anti-tumor necrosis factor (TNF) therapies met the inclusion criteria. The baseline characteristics of the patients assigned to the 3 strategies were not significantly different, except that, as expected, more patients were receiving combination therapy with infliximab. The combination of infliximab plus DMARDs was significantly more effective than etanercept alone for controlling erosion progression (P < 0.001), but the effectiveness of the 2 combination-treatment strategies was similar (P = 0.07). The combination of infliximab plus DMARDs was also more effective at controlling progressive JSN compared with etanercept alone (P = 0.04) or etanercept plus DMARDs (P = 0.02). Treatment with anti-TNF agents (infliximab or etanercept) plus concomitant DMARDs was more effective than treatment with etanercept alone for controlling erosion progression (P = 0.045). CONCLUSION: When combined with traditional DMARDs, both etanercept and infliximab appear to offer similar protection against progressive structural joint damage, and combination therapy with either of these agents appears to be more effective than treatment with etanercept alone.
15938540 [Causes of death in patients with rheumatic diseases in Moscow]. 2005 AIM: To study causes of death of rheumatic patients in Moscow. MATERIAL AND METHODS: Autopsy protocols for 1999-2002 were analysed for two pathoanatomic departments of Moscow. RESULTS: Rheumatic diseases were detected in 165 cases (2.0% of overall number of autopsies in these departments). Rheumatic heart disease (RHD) was stated in 99 (60.0%) cases, rheumatic fever relapse (RFR) in 4 (2.4%), rheumatoid arthritis (RA) in 28 (17.0%), systemic lupus erythematosus (SLE) in 8 (4.8%), systemic sclerosis (SS) in 3 (1.8%), ankylosing spondilarthritis (AS) in 2 (1.2%), systemic vasculitis (SV) in 2 (1.2%), osteoarthrosis in 11 (7.3%), gout in 3 (1.8%), polymyositis in 1 (0.6%). RHD patients died of decompensated circulation (DC) (54%), acute heart failure (AHF) (14%), thromboembolism (TE) (6%), other causes (26%). RF patients died of TE (n = 2), DC (n = 1), AHF (n = 1). Out of 28 RA patients, 5 patients died of secondary amyloidosis, 3 of DC, 7 of AHF, 1 of TE, 5 of infectious complications, 7 of other causes. SLE patients died of uremia (n = 2), acute adrenal failure (n = 1), infectious complications (n = 2), AHF (n = 2), brain edema (n = 1). CONCLUSION: Among rheumatic diseases, rheumatic heart valve disease was most severe as it caused the highest mortality. Cardiovascular pathology caused death in most of the rheumatic patients.
16192902 Interstitial lung disease and neuropathy as predominant extra-articular manifestations in 2005 Oct BACKGROUND: Rheumatoid arthritis (RA) patients with extra-articular manifestations (ExRA) have a severe course of the disease and higher mortality. Indian patients are considered to have a low prevalence of ExRA. We prospectively assessed ExRA in patients with rheumatoid arthritis from southern India. MATERIAL/METHODS: 140 RA patients were qualified for the study. Patients with confounding factors were excluded. A detailed history and clinical examination was performed. Two independent investigators made a thorough search with relevant investigations for ExRA, according to well-defined criteria. RESULTS: At least one ExRA was present in 36 patients (25.7%). The predominant ExRA (9.29%) was Interstitial Lung Disease (ILD). 12 patients had neuropathy (8.57%). 5 patients had eye involvement, while 3 had cutaneous vasculitis. 4 patients had rheumatoid nodules, and 1 had amyloidosis. The median age at diagnosis and duration of disease were significantly higher in patients with ExRAs than in those without. Deformities and the use of steroids were more common in the ExRA cohort. CONCLUSIONS: The present study shows a high prevalence of ILD and neuropathy as ExRAs in our population. A more extensive investigative protocol is warranted for picking up milder presentations of these serious manifestations.
16339290 Declines in number of tender and swollen joints in patients with rheumatoid arthritis seen 2006 Jul OBJECTIVE: To analyse tender and swollen joint counts in three cohorts of patients with rheumatoid arthritis (RA), with a focus on the proportions of patients who had fewer than 6-12 tender or swollen joints, as possible evidence based information toward more generalisable inclusion criteria for current and future RA clinical trials. METHODS: Tender and swollen joint counts were analysed in three cohorts of patients with RA: 125 in 1985, 138 in 2000, and 232 with early RA in 2001. RESULTS: The median numbers of tender joints were 11, 2, and 4 in 1985, 2000, and in early RA in 2001, respectively. The median numbers of swollen joints were 12, 6, and 5 in 1985, 2000, and 2001, respectively. The numbers of tender joints among 28 assessed were >or=12, >or=6, >or=4, and >or=3 in 47%, 80%, 85%, and 90% of patients in 1985; 20%, 37%, 44%, and 49% in 2000; and 17%, 37%, 50%, and 58% in early RA in 2001. The numbers of swollen joints among 28 assessed were >or=12, >or=6, >or=4, and >or=3 in 51%, 78%, 86%, and 90% of patients in 1985; 20%, 50%, 64%, and 67% in 2000; and 14%, 46%, 58%, and 72% in 2001. The number of patients with >or=6 tender or swollen joints in 1985 was greater than the number with >or=3 joints in 2000 and in early RA in 2001. CONCLUSION: Contemporary cohorts of patients seen in standard care have smaller numbers of tender and swollen joints than in previous times. These findings suggest that revision of inclusion criteria for numbers of tender and swollen joints in contemporary RA clinical trials might improve generalisability.
16142711 An independent role of protective HLA class II alleles in rheumatoid arthritis severity an 2005 Sep OBJECTIVE: To prospectively investigate the effect of the DERAA-encoding HLA alleles on disease susceptibility and severity in a large cohort of patients with rheumatoid arthritis (RA), and to differentiate protective effects from non-predisposition by comparing subgroups of patients with an equal amount of predisposition alleles. METHODS: HLA class II alleles were determined in 440 patients with early RA and in 423 healthy controls. In order to study the effect of HLA on disease severity, radiographic joint destruction was evaluated, using the modified Sharp/van der Heijde method, during 4 years of followup. RESULTS: The presence of DERAA-encoding HLA-DRB1 alleles conferred a lower risk of developing RA for both the presence and absence of SE alleles (odds ratio 0.6). At all time points, radiographic destruction was significantly less severe in DERAA-positive patients with 1 SE allele compared with DERAA-negative patients with 1 SE allele. Additionally, a protective effect of DERAA was detected in the groups of patients who were prone to having more severe disease because of the presence of anti-cyclic citrullinated peptide antibodies or because of smoking. CONCLUSION: DERAA-encoding HLA-DRB1 alleles independently protect against RA and are associated with less severe disease.
16877837 Spontaneous esophageal perforation in a patient with achalasia cardia and rheumatoid arthr 2006 May Perforation of stasis ulcers in achalasia cardia has not been reported in literature. We report a 45-year-old lady with achalasia and rheumatoid arthritis who developed perforation and esophago-mediastinal sinus at the site of stasis ulcers. She succumbed to respiratory infection after resection of the sinus tract, Heller's cardiomyotomy, cervical esophagostomy and feeding jejunostomy.
15588973 Imaging in early rheumatoid arthritis: roles of magnetic resonance imaging, ultrasonograph 2005 Feb Efficient methods for diagnosis, monitoring and prognostication are essential in early rheumatoid arthritis (RA). While conventional X-rays only visualize the late signs of preceding disease activity, there is evidence for magnetic resonance imaging (MRI) and ultrasonography being highly sensitive for early inflammatory and destructive changes in RA joints, and for MRI findings being sensitive to change and of predictive value for future progressive X-ray damage. Reviewing the data on X-ray, computed tomography, MRI and ultrasonography in RA, this paper discusses current and future roles of these imaging modalities in the management of early RA. The main focus is on recent advances in MRI and ultrasonography. Suggestions on clinical use and research priorities are provided.
15838240 Understanding the genetic contribution to rheumatoid arthritis. 2005 May PURPOSE OF REVIEW: The identification of the genetic variants that mediate the risk for susceptibility and severity of rheumatoid arthritis will allow the development of new drug targets and also increase the ability to predict disease course. Technical and methodologic progress has fueled the advances in this field. RECENT FINDINGS: The second risk factor for rheumatoid arthritis, the PTPN22 polymorphism, has been identified. This genetic variant regulates the threshold of T cell activation. Intriguingly, this variant is a risk factor for diabetes as well. Moreover, it has been shown that multiple genetic variants in one pathway (both in a transcription factor, RUNX-1, as in the transcription factor binding site of RUNX1 in the SLC22A4 gene) can each confer very small risks but by gene-gene interactions can confer a ninefold risk for rheumatoid arthritis. These genetic risk factors have been found to confer risk for multiple autoimmune diseases. Phenotype-genotype interactions were described by the enhanced prevalence of a rheumatoid arthritis-specific autoantibody (anti-cyclic citrullinated peptide antibodies) in rheumatoid arthritis patients that harbor the rheumatoid arthritis-associated human leukocyte antigen class II genes, the shared epitope alleles. An environmental factor, smoking was demonstrated to confer risk for rheumatoid arthritis, especially in patients positive for both shared epitope and rheumatoid arthritis-specific anti-cyclic citrullinated peptide antibodies. SUMMARY: Two new pathways, T cell receptor signaling and a hematopoietic-specific signal transduction pathway, have been discovered that allow future pharmacologic interventions. The description of the new genetic risk factors and the interaction with environmental triggers as well as phenotypic features are gradually expanding the ability to predict disease susceptibility and course.
15096329 Estimated prediagnosis radiological progression: an important tool for studying the effect 2005 Jan OBJECTIVE: To determine if intrapatient comparisons between prediagnosis and subsequent radiological progression could be used to assess effects of DMARDs in an RA inception cohort. PATIENTS AND METHODS: 149 non-randomised patients with newly diagnosed RA in four groups were analysed: patients treated with (a) methotrexate (n = 56); (b) sulfasalazine (n = 55); (c) auranofin (n = 19); and (d) controls who were poor treatment responders (n = 19). Radiographs were quantified using the Larsen erosion score. The prediagnosis radiological progression from the onset of RA symptoms to diagnosis was calculated and compared with the observed progression rate during the first year after diagnosis while receiving DMARD treatment. RESULTS: Mean (SD) disease duration from onset of symptoms until diagnosis was 6.7 (4.0) months. Mean (SD) baseline Larsen score was 13.2 (9.3), giving a mean (SD) estimated prediagnosis progression rate of 23.6 (12.4) Larsen score units/year. Control and auranofin groups showed radiological progression after diagnosis similar to the progression predicted by prediagnosis progression rates. Patients receiving methotrexate or sulfasalazine showed a marked reduction (71% and 73%, respectively; p<0.001) in radiographic progression compared with prediagnosis progression. CONCLUSIONS: Prediagnosis rates of radiological progression can be used quantitatively to obtain information on the potential efficacy of DMARDs, and indicate that methotrexate and sulfasalazine, but not auranofin, significantly retard radiographic damage in the first year after diagnosis.
15608311 Predictors of productivity loss in early rheumatoid arthritis: a 5 year follow up study. 2005 Jan OBJECTIVE: To explore baseline risk factors for productivity loss and work disability over 5 years in patients with early, active RA. PATIENTS AND METHODS: In the FIN-RACo trial, 195 patients with recent onset RA were randomised to receive either a combination of DMARDs with prednisolone or a single DMARD for 2 years. At baseline, 162 patients were working or available for work. After 5 years' follow up, data on sick leave and retirement were obtained from social insurance registers or case records. The cumulative duration of sick leaves and RA related disability pensions was counted for each patient. To analyse predictors of productivity loss, the patients were divided into four groups according to duration of work disability per patient year. RESULTS: Patient's and physician's global assessment of RA severity > or =50 and HAQ score > or =1.0 were risk factors for extension of productivity loss (OR (95% (CI) 1.77 (1.00 to 3.16), 1.85 (1.03 to 3.32), and 1.78 (1.01 to 3.14), respectively). Additional risk factors were low education level (2.40 (1.18 to 4.88)) and older age (1.03 (1.00 to 1.06)); combination treatment was a protective factor (0.59 (0.35 to 0.99)). CONCLUSION: At baseline, the risk of future productivity loss is best predicted by education level, age, global assessments of RA severity, and HAQ score.
15731287 Investigation of polymorphisms in the PADI4 gene in determining severity of inflammatory p 2005 Sep BACKGROUND: A functional haplotype of the peptidylarginine deiminase 4 (PADI4) gene has recently been identified as a rheumatoid arthritis susceptibility gene in a Japanese but not in a UK population. One possible explanation for this disparity is that the gene determines severity of rather than susceptibility to inflammatory polyarthritis (IP) and that the UK and Japanese cohorts differed in terms of outcome. AIM: To examine the association between individual PADI4 single nucleotide polymorphisms (SNPs) and haplotypes, with the development and severity of erosions by five years in patients with IP. METHODS: 438 patients from the NOAR inception cohort of patients with IP were x rayed five years after presentation with early IP. Association with four exonic SNPs (padi4_89*G/A, padi4_90*T/C, padi4_92*G/C, and padi4_104*T/C), mapping to the PADI4 gene and defining a haplotype previously reported to be associated with rheumatoid arthritis, was investigated. Patients were compared for the presence, extent, and progression of erosions by five years and the presence of antibodies to citrullinated peptide (anti-CCP antibodies). RESULTS: There was no association between individual PADI4 SNPs or haplotypes and the development or extent of erosions by five years. Restricting analysis to patients who satisfied ACR criteria for rheumatoid arthritis by five years did not alter the conclusions. No association with presence of anti-CCP antibodies was detected. CONCLUSIONS: No evidence was found for association of the PADI4 gene with severity as assessed by erosive outcome at five years or with presence of anti-CCP antibodies in patients with IP.
16828289 Flexion after total knee replacement. A comparison between the Medial Pivot knee and a pos 2006 Oct A comparison was made between 261 knees replaced with the Medial Pivot arthroplasty and 288 replaced with the 913 posterior stabilised arthroplasty (PS knee). There was no significant difference in the flexion obtained at 12 months after surgery (111 degrees and 109 degrees , respectively). When the knees were grouped into preoperative flexion ranges, there was no significant difference between the two implants. Those knees with preoperative flexion up to 90 degrees gained most (mean 22.6 degrees and 19 degrees for the PS knee and Medial Pivot, respectively). Knees with a preoperative flexion of 125 degrees or greater lost flexion. Regression analysis of individual knees revealed a small (average 2.9 degrees ), but significant greater loss of flexion at 12 months after surgery in the Medial Pivot group, with increasing preoperative flexion (beta coefficient = 2.923, P = 0.007). Some knees in both groups which had less than average preoperative flexion lost rather than gained flexion. We attributed this to patient factors such as pain, swelling and poor compliance with rehabilitation. Although the Medial Pivot knee may have advantages in terms of contact area and kinematics we found no advantage in terms of postoperative flexion over our posterior stabilised knee.
16041739 Efficacy and tolerance of atrisin in degenerative and inflammatory joint disorders. 2005 Apr In a randomized multi-centre clinical trial the efficacy and tolerance of a herbal product Atrisin three capsules/day was evaluated in 65 patients (31 male, 34 female) suffering from osteoarthritis and rheumatoid arthritis, during a period of 2 months. Assessment of pain and functional disability were made on a 10 cm horizontal visual analogue scale. The severity of osteoarthritis was evaluated by Lequesne's index.Spontaneous pain showed significant improvement. Similarly there was progressive and significant reduction in the Lequesne's functional index. At the completion of the study patients taking Atrisin were using less NSAIDs. Atrisin was tolerated well by the patients and there were no adverse cardiovascular or gastric effects reported. There was feeling of general well-being and compliance by the patients.
17133580 The functional variant of the inhibitory Fcgamma receptor IIb (CD32B) is associated with t 2006 Dec OBJECTIVE: Fcgamma receptors (FcgammaRs) recognize immune complexes (ICs) and coordinate the immune response by modulating the functions of dendritic cells (DCs). The purpose of this study was to unravel the role of the inhibitory FcgammaRIIb in rheumatoid arthritis (RA) by studying the effect of the FCGR2B 695T>C polymorphism on susceptibility to RA, severity of the disease, and DC function. METHODS: Genotyping was performed in RA patients (n = 246) and healthy blood donors (n = 269). The patients' demographic data, disease severity, and disease progression were assessed over a followup of 6 years. DCs were cultured for flow cytometry to determine the expression of FcgammaRs. For detection of FcgammaRIIb (CD32B), a unique anti-FcgammaRIIb antibody (2B6-fluorescein isothiocyanate [FITC]) was used. The capacity for antigen uptake by DCs was studied by assessing the uptake of FITC-labeled ICs. Levels of cytokine production by DCs were measured during lipopolysaccharide-mediated cell activation in the presence and absence of ICs. RESULTS: Although no role of the FCGR2B variant in RA susceptibility was demonstrated, this variant was associated with a nearly doubled rate of radiologic joint damage during the first 6 years of RA. Multiple regression analysis showed that FCGR2B was by far the strongest predictor of joint damage identified to date. DCs from patients carrying this variant failed to display the inhibitory phenotype normally observed upon IC-mediated triggering of inflammation and displayed diminished FcgammaRII-mediated antigen uptake compared with wild-type DCs. However, the levels of FcgammaRs were not affected, suggesting that the FCGR2B variant alters the function rather than regulation of proteins. CONCLUSION: This study is the first to show that a single genetic variant, the FCGR2B 695T>C polymorphism, is a critical determinant of disease severity in RA and radically changes DC behavior. Our results underscore the key role of DCs in the progression of RA and reveal FcgammaRIIb as an important potential therapeutic target in RA and other autoimmune conditions.
17064527 [Study of the proteins associated with Sa antigen]. 2006 Jul 18 OBJECTIVE: To study the proteins associated with Sa antigen, a target of the anti-Sa antibodies specific for rheumatoid arthritis, and to elucidate the nature of these proteins. METHODS: Sa antigen was extracted from fresh human placental tissue by anion exchange chromatography and subjected to SDS-PAGE electrophoresis. Serum samples were collected from 155 patients with connective tissue diseases, including rheumatoid arthritis (71 cases), ankylosing spondylitis (11 cases), psoriatic arthritis (7 cases), reactive arthritis (7 cases), juvenile idiopathic arthritis (4 cases), osteoarthritis (5 cases), polymyalgia rheumatica (6 cases), gout (6 cases), systemic lupus erythematous (7 cases), Sjogren's syndrome (10 cases), adult onset Still's disease (3 cases) and Sa antibodies were detected by immunoblotting. The gel bands corresponding to the stained bands were excised, trypsin-digested in gel, and analyzed by LC-ESI-MS/MS. Once identified, the protein was recombinate and expressed in Escherichia coli, and the antibodies were detected by immunoblotting. Then the protein was citrullinated to detect the antibodies again. RESULTS: Immunoblotting showed anti-Sa antibodies, band (s) with apparent molecular weight of 50 000 (and) 55 000, in 34 of the 71 patients of rheumatoid arthritis and 4 of the 84 patients of other rheumatic diseases, with a sensitivity rate of 47.9% and a specificity rate of 95.2%. The target protein was identified as vimentin. The positive rate of anti-vimentin antibody was statistically different between the RA patients and the patients with other rheumatic diseases (P = 0.005), with a sensitivity rate of 36.6% and a specificity rate of 83.3%, respectively. But there was no obvious correlation between anti-vimentin antibody and anti-Sa antibodies (Kappa = 0.316). The positive rate of anti-citrullinated vimentin antibody was significantly higher in the RA patients than in the patients with other rheumatic diseases (P < 0.01), with a sensitivity rate of 49.3%. There was a high correlation between anti-citrullinated vimentin antibody and anti-Sa antibodies (Kappa = 0.746), albeit a low specificity rate (86.9%). CONCLUSION: Citrullinated vimentin is closely correlated with Sa antigen.
16414468 Shoulder arthroplasty in Olmsted County, Minnesota, 1976-2000: a population-based study. 2006 Jan Because little information is currently available on the epidemiology of shoulder arthroplasty, this study was designed to evaluate the characteristics of patients undergoing this procedure and changes in practice patterns. Residents of Olmsted County, Minnesota, who underwent shoulder arthroplasty between 1976 and 2000 were identified (98 residents, 112 procedures). A relatively lower initial rate of shoulder arthroplasty was followed by a statistically significant steady increase (P < .0001), with an age- and sex-adjusted annual operative incidence rate of 1.4 per 100,000 person-years (1976-1980) to 10.1 per 100,000 person-years (1996-2000). Increased utilization of shoulder arthroplasty during the last decade was mainly a result of its application in osteoarthritis. A significant need exists for examination of utilization patterns for shoulder arthroplasty. An aging population and an increased demand and awareness by the public regarding interventions to improve quality of life will shape the future of arthroplasty, reinforcing the need for future studies of this nature.
18666383 Clinical pharmacogenomics of thiopurine S-methyltransferase. 2006 Jan Thiopurine methyltransferase (TPMT) catalyzes the S-methylation of thiopurine drugs such as 6-mercaptopurine (6-MP), thioguanine and azathioprine (AZA). These drugs are used to treat conditions such as acute lymphoblastic leukemia, inflammatory bowel disease, rheumatoid arthritis, and organ transplant rejection. This review highlights the polymorphisms of TPMT gene and their clinical impact on the use of thiopurine drugs. To date, there are 18 known mutational TPMT alleles. The three main TPMT alleles, namely TPMT *2, *3A and *3C, account for 80 - 95% of the intermediate and low enzyme activity. The TPMT gene exhibits significant genetic polymorphisms among all ethnic groups studied. Patients who inherited very low levels of TPMT activity are at greatly increased risk for thiopurine-induced toxicity such as myelosuppression, when treated with standard doses of these drugs, while subjects with very high activity may be undertreated. Moreover, clinical drug interactions may occur due to TMPT induction or inhibition. Identification of the TPMT mutant alleles allows physicians to tailor the dosage of the thiopurine drugs to the genotype of the patient or to use alternatives, improving therapeutic outcome.
15760928 Functional haplotypes of PADI4: relevance for rheumatoid arthritis specific synovial intra 2005 Sep BACKGROUND: Haplotypes of PADI4, encoding for a citrullinating enzyme, were associated with rheumatoid arthritis in a Japanese population. It was suggested they were related to the presence of anticitrullinated protein antibodies (ACPA). OBJECTIVE: To explore the relation between PADI4 haplotypes, the presence of rheumatoid arthritis specific intracellular citrullinated proteins in synovial membrane, and serum ACPA titres. METHODS: Synovial biopsies and peripheral blood samples were obtained in 59 patients with rheumatoid arthritis. Synovial intracellular citrullinated proteins were detected by immunohistochemistry. Serum ACPA titres were measured by anti-CCP2 ELISA. PADI4 haplotypes were determined by direct sequencing of the four exonic PADI4 single nucleotide polymorphisms. RESULTS: PADI4 haplotype frequencies and the presence of synovial intracellular citrullinated proteins and ACPA were comparable with previous studies. There was no significant association between PADI4 haplotype 1 or 2 and the presence of synovial intracellular citrullinated proteins, although these proteins were associated with higher serum ACPA. There was no correlation between PADI4 haplotypes and serum ACPA, either by continuous analysis using the titres or by dichotomous analysis using the diagnostic cut off. Further analyses in homozygotes for haplotype 1 or 2 or in heterozygotes (1/2) also failed to show an association between PADI4 polymorphisms and ACPA. This contrasted with the clear association between ACPA levels and HLA-DR shared epitope. CONCLUSIONS: The link between synovial intracellular citrullinated proteins and ACPA emphasises the role of deimination of synovial proteins in rheumatoid arthritis, but the biological relevance of the PADI4 haplotypes for this autoimmune process is questionable, at least in a European population.
17040961 Resistin in rheumatoid arthritis synovial tissue, synovial fluid and serum. 2007 Apr BACKGROUND: Resistin is a newly identified adipocytokine which has demonstrated links between obesity and insulin resistance in rodents. In humans, proinflammatory properties of resistin are superior to its insulin resistance-inducing effects. OBJECTIVES: To assess resistin expression in synovial tissues, serum and synovial fluid from patients with rheumatoid arthritis, osteoarthritis and spondylarthropathies (SpA), and to study its relationship with inflammatory status and rheumatoid arthritis disease activity. METHODS: Resistin expression and localisation in synovial tissue was determined by immunohistochemistry and confocal microscopy. Serum and synovial fluid resistin, leptin, interleukin (IL)1beta, IL6, IL8, tumour necrosis factor alpha, and monocyte chemoattractant protein-1 levels were measured. The clinical activity of patients with rheumatoid arthritis was assessed according to the 28 joint count Disease Activity Score (DAS28). RESULTS: Resistin was detected in the synovium in both rheumatoid arthritis and osteoarthritis. Staining in the sublining layer was more intensive in patients with rheumatoid arthritis compared with those with osteoarthritis. In rheumatoid arthritis, macrophages (CD68), B lymphocytes (CD20) and plasma cells (CD138) but not T lymphocytes (CD3) showed colocalisation with resistin. Synovial fluid resistin was higher in patients with rheumatoid arthritis than in those with SpA or osteoarthritis (both p<0.001). In patients with rheumatoid arthritis and SpA, serum resistin levels were higher than those with osteoarthritis (p<0.01). Increased serum resistin in patients with rheumatoid arthritis correlated with both CRP (r=0.53, p<0.02), and DAS28 (r=0.44, p<0.05), but not with selected (adipo) cytokines. CONCLUSION: The upregulated resistin at local sites of inflammation and the link between serum resistin, inflammation and disease activity suggest a role for resistin in the pathogenesis of rheumatoid arthritis.