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ID PMID Title PublicationDate abstract
16328088 New-onset demyelination induced by infliximab therapy in two rheumatoid arthritis patients 2006 Nov Therapies aimed at inhibiting tumor necrosis factor, a proinflammatory cytokine implicated in autoimmune disease, are effective for rheumatoid arthritis (RA) and Crohn's disease. We report two patients who newly developed multiple demyelinating lesions in the central nervous system in the course of infliximab therapy for active RA. Neurological symptoms and the number of gadolinium-diethylenetriamine pentaacetic acid-enhanced lesions in magnetic resonance imaging gradually diminished with steroid treatment.
16283307 Early polyethylene wear and osteolysis with ABG acetabular cups (7- to 12-year follow-up). 2006 Feb We reviewed 81 consecutive ABG I primary total hip replacements implanted in 72 patients between January 1993 and December 1998. The mean follow-up was 8.2 (range 7-12) years. There was significant polyethylene wear and osteolysis associated with the acetabular cup . The cumulative survival of the cup with revision being the end point at 8.2 years was 95.1% (95% CI: 92-97.6%). However, the cumulative survival of the cup with revision and aseptic loosening together was 72% (95% CI: 61-78%) and survival of the acetabular liner for wear was 62% (95% CI: 48-74%). Stem survival with revision being the end point was 100%. In spite of significant radiological failures of the cups, most patients remained asymptomatic. Though results of the ABG stems in this series were good, we advocate a regular follow-up of all these hips in view of the poor outcome of the cups.
16670074 Atypical lymphoproliferation progressing into B-cell lymphoma in rheumatoid arthritis trea 2006 May A patient with rheumatoid arthritis (RA) developed an atypical lymphoproliferative disorder (LPD) after methotrexate and cyclosporine A, which regressed after suspension of both drugs. After subsequent treatment with rituximab, the LPD was still undetectable. Anti-tumor necrosis factor a therapy was used when the arthritis relapsed, but an aggressive B-cell non Hodgkin's lymphoma developed. Molecular analyses showed an oligoclonal B-cell expansion at the LPD step. A minor clone with significant sequence homology to B-cell lymphomas arising in Sjogren's syndrome and mixed cryoglobulinemia syndrome, given rise to the non-Hodgkin's lymphoma. Treatment of rheumatoid arthritis associated with lymphoproliferation represents a clinical challenge, and common pathogenetic pathways to lymphoma may occur in different autoimmune diseases.
15809950 Effect of tourniquet pressure on perioperative blood loss associated with cementless total 2005 Apr Perioperative blood loss is an issue of concern in cementless total knee arthroplasty (TKA). We randomly assigned 57 patients (60 knees) who underwent cementless TKA treatment to 2 groups with tourniquet pressure (TP) of either 350 mm Hg (30 knees) or systolic blood pressure (SBP) plus 100 mm Hg (30 knees) to assess the effect of TP on blood loss. The mean TP in the SBP plus 100 mm Hg group was 238 +/- 13 mm Hg. There was no significant difference between groups. Red blood cell count, hemoglobin levels, and hematocrit recovered to preoperative levels by 3 months after surgery in both groups. In conclusion, we recommend using a TP of 100 mm Hg above SBP during TKA, rather than using the conventional TP of 350 mm Hg.
16385499 Association between protein tyrosine phosphatase 22 variant R620W in conjunction with the 2006 Jan OBJECTIVE: To analyze the genetic impact of allelic variants of the protein tyrosine phosphatase N22 (PTPN22) and HLA-DRB1 alleles on IgG autoantibody formation directed toward an immunodominant conformational epitope (C1(III); amino acid residues 359-369) of type II collagen (CII) in early rheumatoid arthritis (RA). METHODS: Sera obtained at study inclusion from an inception cohort of RA patients (n = 221; mean symptom duration 6 months) were analyzed for circulating anti-C1(III) IgG autoantibodies. An enzyme-linked immunosorbent assay based on solid-phase-coupled synthetic triple-helical collagen peptides was used to quantify humoral autoimmune responses. HLA-DRB1 genotypes were determined by allele-specific polymerase chain reaction amplification of genomic DNA and sequence-specific hybridization. PTPN22*620W genotyping was performed using an allelic discrimination TaqMan assay. RESULTS: Anti-C1(III) IgG autoantibody titers were significantly elevated in patients with early RA as compared with those in healthy controls (n = 70). The increased titers were more pronounced in RA patients harboring alleles of the RA-associated HLA-DRB1 shared epitope (SE) consensus sequence than in those lacking the SE. In addition, the PTPN22*620W variant was strongly associated with a vigorous humoral autoimmune response to the cartilage-specific CII determinant C1(III). CONCLUSION: Allelic variants encoding the binding pocket for peptide presentation (SE) to T cells and a functional domain of a negative regulator of T cell receptor signaling (PTPN22*620W), respectively, synergize in early RA to break self tolerance toward C1(III), an evolutionarily conserved cartilage determinant that is also frequently targeted in arthritogenic humoral autoimmunity in mice.
17412304 Safety and efficacy of vaccination against streptococcus pneumonia in patients with rheuma 2007 Apr Vaccination against streptococcus pneumonia is currently recommended for patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Safety and efficacy issues of vaccination in patients suffering from rheumatic diseases are still unresolved. This review summarizes the studies performed on the safety and immunogenicity of pneumococcal vaccination in patients with RA and SLE, with special emphasis on the effect of immunosuppressive drugs on the efficacy of the vaccine. Several trials have shown that the vaccine does not induce clinical exacerbation of RA and that it does induce an adequate humoral response, albeit one lower than that in healthy controls.
16426246 Promoter polymorphism rs3087456 in the MHC class II transactivator gene is not associated 2006 Feb We analysed whether the single nucleotide polymorphism (SNP) rs3087456 in the promoter of the MHC class II transactivator (MHC2TA) gene is associated with manifestation of rheumatoid arthritis, multiple sclerosis, narcolepsy and Wegener granulomatosis. The recently reported association in a northern population of the MHC2TA variation with these autoimmune diseases is not evident in the German population.
16690762 Are rheumatologists' treatment decisions influenced by patients' age? 2006 Dec OBJECTIVES: The objective of this study was to determine whether physicians' treatment preferences are influenced by patients' age. METHODS: We mailed a survey to a random sample of rheumatologists practicing in the US. The survey included a scenario describing a hypothetical patient with rheumatoid arthritis (RA) on hydroxychloroquine, sulfasalazine and low-dose prednisolone, who presents with active disease during a follow-up appointment. The scenario was formulated in two versions that were identical except for the age of the patient. After reading the scenario, respondents were asked to rate (on a 10 cm numerical rating scale) their recommendations for each of the three options: (i) increasing the dose of prednisolone, (ii) adding a new disease-modifying anti-rheumatic drug (DMARD) and (iii) switching DMARDs. Rheumatologists who rated either adding a new DMARD or switching DMARDs higher than increasing the dose of prednisolone were classified as 'preferring aggressive treatment with DMARDs', while the others were classified as 'NOT preferring aggressive treatment with DMARDs'. RESULTS: A total of 480 rheumatologists were mailed a questionnaire; 204 responded, giving a response rate of 42.5%. Overall 163 (80%) respondents were classified as preferring aggressive treatment with DMARDs. Rheumatologists responding to this survey were more likely to prefer aggressive DMARD treatment for the young RA patient vs the older RA patient (87 vs 71%, P= 0.007). CONCLUSIONS: Our findings suggest that rheumatologists' treatment recommendations may be influenced by age. Future educational efforts should increase physician awareness of this possible bias in order to ensure equal service delivery across ages.
15743491 Transforming growth factor-beta-induced regulatory T cells referee inflammatory and autoim 2005 Naturally occurring CD4+CD25+ regulatory T cells mediate immune suppression to limit immunopathogenesis associated with chronic inflammation, persistent infections and autoimmune diseases. Their mode of suppression is contact-dependent, antigen-nonspecific and involves a nonredundant contribution from the cytokine transforming growth factor (TGF)-beta. Not only can TGF-beta mediate cell-cell suppression between the regulatory T cells and CD4+CD25- or CD8+ T cells, but new evidence also reveals its role in the conversion of CD4+CD25- T cells, together with TCR antigen stimulation, into the regulatory phenotype. Elemental to this conversion process is induction of expression of the forkhead transcription factor, Foxp3. This context-dependent coercion of naive CD4+ T cells into a powerful subset of regulatory cells provides a window into potential manipulation of these cells to orchestrate therapeutic intervention in diseases characterized by inadequate suppression, as well as a promising means of controlling pathologic situations in which excessive suppression dominates.
15878901 Expression of interferon beta in synovial tissue from patients with rheumatoid arthritis: 2005 Dec BACKGROUND: IFNbeta may have immunomodulatory effects in rheumatoid arthritis (RA) and its increased production in RA synovium may be a reactive attempt to inhibit inflammation. OBJECTIVE: To determine the expression of IFNbeta in the synovial tissue of patients with RA, osteoarthritis, and reactive arthritis. METHODS: Synovial biopsy specimens were obtained by arthroscopy from patients with RA and disease controls for immunohistological analysis using a monoclonal antibody specific for IFNbeta. Bound antibody was detected by an immunoperoxidase method. Stained sections were evaluated by computer assisted image analysis. Double stainings were performed with antibodies to detect CD55 positive fibroblast-like synoviocytes (FLS), CD68 positive macrophages, and CD83 positive dendritic cells (DCs) co-expressing IFNbeta. RESULTS: IFNbeta protein was abundantly expressed in the synovium of patients with RA. Digital image analysis showed a significant increase in the mean integrated optical density for IFNbeta expression in RA synovial tissue compared with disease controls. Specific up regulation of IFNbeta expression was also seen when the results were controlled for cell numbers. Phenotypic analysis showed that FLS, especially, but also macrophages and DCs may express IFNbeta in RA synovial tissue. CONCLUSIONS: The increased expression of IFNbeta in RA synovium suggests activation of an immunomodulatory mechanism that could inhibit synovial inflammation.
16257178 Redefining the HLA and RA association: to be or not to be anti-CCP positive. 2005 Rheumatoid Arthritis (RA) is the most common chronic inflammatory joint disease. The overall prevalence is 1% and in people older than 60 it is more than 2%. RA has auto-immune features: auto-antibodies against the Fc part of IgG, so-called Rheumatoid Factor (RF) are found more often in RA patients and more recently RA-specific auto-antibodies directed against Cyclic Citrunilated Peptides (CCP) have been discovered. Based on twin studies the contribution of genetic factors to the pathogenesis has been estimated to be about 60%. The main genetic contribution (about 40%) comes from the HLA complex. An association between HLA-DR4 and RA was already documented almost 30 years ago. This association was more prominent for severe forms of the disease. Because more HLA-DRB1 alleles appeared to be associated with RA and the products of these alleles shared a 5AA sequence in a peptide-binding pocket the so-called Shared Epitope (SE) hypothesis was formulated, the prediction being that these DRB1 molecules would bind an RA inducing peptide(s). Thus far however such (a) peptides remain elusive. Because the risk for RA associated with different but SE-identical DRB1 alleles varies considerably this SE can also not be the whole explanation for the HLA contribution to RA susceptibility/severity. A modified SE has been postulated and a role for DQ has been postulated. There is also evidence for a contribution of non-class II genes to susceptibility. About 5 years ago we have reported that certain HLA-DRB1 alleles are associated with protection from (severe) RA. The products of these alleles carry instead of the SE sequence another peptide anchor region consisting of the amino acid DERAA. In a large prospective cohort study we showed recently that these alleles indeed confer (dominant) protection both against developing RA and a severe course of the disease. This protection was observed both in the presence and the absence of SE susceptibility alleles. We are presently exploring the hypothesis that this protection is mediated by regulatory T cells reactive with the DERAA epitope. An obvious way to unravel the apparently complex association between HLA and RA is to reduce the heterogeneity of this multifactorial disease. Recently, we have discovered that SE positive DRB1 alleles are exclusively associated with CCP positive RA. The previously reported association with RF positive RA appeared to be secondary to the association with anti-CCP pos. RA. This was the case both for the association found for susceptibility and severity. Interestingly, DRB1*03 was exclusively associated with anti-CCP neg. RA. Because recent evidence puts the immune response against citrunilated proteins (CCP) as prime suspect for disease induction and progression in this subgroup of RA these observations are a big leap forwards in solving the HLA-RA puzzle.
16192640 Analysis of in vivo role of alpha-fodrin autoantigen in primary Sjogren's syndrome. 2005 Oct The alpha-fodrin N-terminal portion (AFN) autoantigen mediates in vivo immunoregulation of autoimmune responses in primary Sjögren's syndrome (SS). We further examined this process and found that cleavage products of AFN were frequently detected in the salivary gland duct cells of SS patients. In in vitro studies using human salivary gland HSY cells, anti-Fas-induced apoptosis resulted in specific cleavage of alpha-fodrin into the 120-kd fragment, in association of alpha-fodrin with mu-calpain, and activation of caspase 3. Significant proliferative responses against AlphaFN autoantigen were observed in the peripheral blood mononuclear cells (PBMCs) from SS patients with higher pathological score (grade 4) and with short duration from onset (within 5 years). In vivo roles of AFN peptides were investigated using PBMCs from patients with SS, systemic lupus erythematosus, and rheumatoid arthritis. Significant proliferative T-cell responses of PBMCs to AFN peptide were detected in SS but not in systemic lupus erythematosus or rheumatoid arthritis. AFN peptide induced Th1-immune responses and accelerated down-regulation of Fas-mediated T-cell apoptosis in SS. Our data further elucidate the in vivo role of AFN autoantigen on the development of SS and suggest that the AFN autoantigen is a novel participant in peripheral tolerance.
16891223 Frequency and significance of antibodies to cyclic citrullinated peptide in type 1 autoimm 2006 Jun OBJECTIVES: Determine the frequency, clinical phenotype, and prognostic implications of antibodies against cyclic citrullinated peptides in patients with type 1 autoimmune hepatitis. METHODS: Three hundred and ninety-five serum samples from 179 patients were tested by enzyme-linked immunosorbent assay, and findings correlated with clinical and histological features, frequency of HLA DR3 and DR4, and treatment outcome. RESULTS: Twenty patients (11%) had antibodies against cyclic citrullinated peptides. Seropositivity was associated with a higher frequency of rheumatoid arthritis (RA) (25 vs. 0%, P < 0.001). Patients with antibodies against cyclic citrullinated peptides also had a significantly greater occurrence of histological cirrhosis at presentation (47 vs. 20%, P = 0.01) and death from hepatic failure than seronegative patients (25 vs. 9%, P = 0.04). Cirrhosis at presentation occurred more commonly in the patients with antibodies against cyclic citrullinated peptides and RA than in the other patients (100 vs. 21%, P = 0.005). CONCLUSIONS: Antibodies against cyclic citrullinated peptides occur in a subgroup of patients with type 1 autoimmune hepatitis who have a greater occurrence of cirrhosis at presentation and death from hepatic failure. Their presence with RA at accession characterizes a subgroup with cirrhosis.
16351704 Older women and dietary advice: occurrence, comprehension and compliance. 2005 Dec BACKGROUND: When a person becomes ill, traditional food habits may come into conflict with the disease-related recommended diet. AIM: The aim was to study perceptions of receiving dietary advice, the occurrence and comprehension of such advice and compliance among older women diagnosed with Parkinson's disease, stroke or rheumatoid arthritis. METHODS: The study took an ethnographic approach. Fifty-four community-dwelling women, 64-88 years of age, were interviewed using an open-ended interview technique during visits to their homes. FINDINGS: Two themes were found: 'dietary advice - occurrence and comprehension' describes whether the women had received dietary advice and, if so, how they understood the information. In the theme 'compliance with dietary advice', two principal reasons for complying or not complying with advice were found: First, women expressed a 'food interest', such that they were either 'interested in disease-related diet' or held a general view of the significance of foods and complied with the advice for their own 'health interest'. Secondly, the women were 'uninterested in food changes'. This could be because of 'poor appetite', 'food and disease ambivalence', 'habitual and preferred foods'. CONCLUSION: Dietary advice should be based on women's food preferences and habitual foods. It is important to inform about known relations between food and disease, but also to support eating favourite foods, thereby facilitating women's well-being.
16511935 Neurological complications of infliximab. 2006 May The use of anti-tumor necrosis factor-a (TNF-a) therapies has led to improved outcomes in the treatment of rheumatoid arthritis (RA). However, the use of these new therapeutic agents requires careful monitoring for adverse effects. We describe 3 patients who developed neurological disease closely associated with the use of infliximab, a monoclonal antibody that binds to and inactivates TNF-a. All had evidence of polyneuropathy, demyelinating in one and axonal in 2. One patient had a central nervous system syndrome. Physicians should be aware of these potential adverse effects when treating patients with infliximab.
16814399 Mannan binding lectin and its interaction with immunoglobulins in health and in disease. 2006 Aug 15 In humans there are five classes of immunoglobulins (Igs), IgG, IgM, IgA, IgE and IgD, all of which are glycoproteins. The Igs are the major secretory product of the adaptive immune system, and they bind to antigens via variable sequences on their Fab regions. The binding to antigen results in neutralization or agglutination of bound material and also initiates effector functions via the Fc regions, such as opsonisation and activation of the classical complement pathway through binding of C1q. Mannan binding lectin (MBL), the 'recognition' molecule of the lectin pathway of complement activation, is homologous in structure to C1q, and binds in a calcium-dependent manner to terminal mannose and GlcNAc residues which have been identified on the oligosaccharides N-linked to the Igs. MBL binds agalactosylated glycoforms of IgG (IgG-G0), polymeric forms of IgA and certain glycoforms of IgM which have a high incidence of GlcNAc-terminating glycans. This interaction provides a route of clearance of immune complexes from the serum, and a mechanism of complement activation to Ig-coated pathogens. In disease, MBL contributes to inflammation in Rheumatoid Arthritis, a condition in which serum IgG-G0 concentrations can increase significantly compared to healthy individuals. MBL has recently been demonstrated to bind Ig in the B cell receptor complex which expresses abnormal variable region glycosylation, in follicular lymphoma.
16271148 A rigorous method for multigenic families' functional annotation: the peptidyl arginine de 2005 Nov 4 BACKGROUND: large scale and reliable proteins' functional annotation is a major challenge in modern biology. Phylogenetic analyses have been shown to be important for such tasks. However, up to now, phylogenetic annotation did not take into account expression data (i.e. ESTs, Microarrays, SAGE, ...). Therefore, integrating such data, like ESTs in phylogenetic annotation could be a major advance in post genomic analyses. We developed an approach enabling the combination of expression data and phylogenetic analysis. To illustrate our method, we used an example protein family, the peptidyl arginine deiminases (PADs), probably implied in Rheumatoid Arthritis. RESULTS: the analysis was performed as follows: we built a phylogeny of PAD proteins from the NCBI's NR protein database. We completed the phylogenetic reconstruction of PADs using an enlarged sequence database containing translations of ESTs contigs. We then extracted all corresponding expression data contained in EST database This analysis allowed us 1/To extend the spectrum of homologs-containing species and to improve the reconstruction of genes' evolutionary history. 2/To deduce an accurate gene expression pattern for each member of this protein family. 3/To show a correlation between paralogous sequences' evolution rate and pattern of tissular expression. CONCLUSION: coupling phylogenetic reconstruction and expression data is a promising way of analysis that could be applied to all multigenic families to investigate the relationship between molecular and transcriptional evolution and to improve functional annotation.
15866972 Revision of unstable capitellocondylar (unlinked) total elbow replacement. 2005 May BACKGROUND: Instability is a recognized complication associated with unlinked total elbow implants. The best form of treatment of this problem is uncertain as very little has been written about it. METHODS: Twelve patients underwent operative treatment of instability at the site of a capitellocondylar unlinked total elbow replacement, and the results were reviewed retrospectively. The study group included ten women and two men with an average age of fifty-eight years. Ten patients had rheumatoid arthritis. Three elbows underwent conversion to a semi-constrained hinged prosthesis. In the other nine elbows, an attempt was made to continue with an unlinked prosthesis: three had reconstruction of one or both collateral ligaments, four had component revision, and two had both ligament reconstruction and component revision. RESULTS: After an average duration of follow-up of six years (range, two to fifteen years) only three patients had retained a functioning unlinked prosthesis. Of the remaining nine patients, three had had a conversion to a semi-constrained arthroplasty at the time of the index procedure, four had had a conversion to a semi-constrained prosthesis at the time of a salvage procedure, one had had a resection arthroplasty, and one had a painfully dislocated elbow and had declined revision. Thus, seven elbows eventually underwent conversion to a semi-constrained prosthesis; these conversion procedures were technically difficult, with perforation of the humerus occurring in six patients and perforation of the ulna occurring in four. After all procedures, the average elbow flexion was 132 degrees and the average flexion contracture was 25 degrees. According to the Mayo Elbow Performance Index, there were four excellent results, three good results, three fair results, and one poor result. CONCLUSIONS: Revision of an unlinked total elbow prosthesis to a linked total elbow prosthesis is difficult, but it restores elbow function. Although the present series documents the unpredictability of attempts to salvage an unstable unlinked prosthesis, it seems reasonable to attempt at least one soft-tissue procedure before converting to a linked prosthesis.
15297282 First clinical evaluation of sagittal laser optical tomography for detection of synovitis 2005 Feb OBJECTIVE: To identify classifiers in images obtained with sagittal laser optical tomography (SLOT) that can be used to distinguish between joints affected and not affected by synovitis. METHODS: 78 SLOT images of proximal interphalangeal joints II-IV from 13 patients with rheumatoid arthritis were compared with ultrasound (US) images and clinical examination (CE). SLOT images showing the spatial distribution of scattering and absorption coefficients within the joint cavity were generated. The means and standard errors for seven different classifiers (operator score and six quantitative measurements) were determined from SLOT images using CE and US as diagnostic references. For classifiers showing significant differences between affected and non-affected joints, sensitivities and specificities for various cut off parameters were obtained by receiver operating characteristic (ROC) analysis. RESULTS: For five classifiers used to characterise SLOT images the mean between affected and unaffected joints was statistically significant using US as diagnostic reference, but statistically significant for only one classifier with CE as reference. In general, high absorption and scattering coefficients in and around the joint cavity are indicative of synovitis. ROC analysis showed that the minimal absorption classifier yields the largest area under the curve (0.777; sensitivity and specificity 0.705 each) with US as diagnostic reference. CONCLUSION: Classifiers in SLOT images have been identified that show statistically significant differences between joints with and without synovitis. It is possible to classify a joint as inflamed with SLOT, without the need for a reference measurement. Furthermore, SLOT based diagnosis of synovitis agrees better with US diagnosis than CE.
16925056 [Impact of sodium chloride concentration on pH-metricdetermination of the rate of erythroc 2006 Jul The impact of the concentration of a base electrolyte (0.57; 0.85, 2.28% NaCl) on the pH-metric study of ionic equilibrium was studied in theerythrocytic suspensions obtained from the peripheral blood of healthy individuals, patients with various diseases and in the latter after their treatment. The use of the isotonic concentration of the base electrolyte at an ionic force of micro = 0.15 (0.85% NaCl) is optimal in terms of the accuracy of establishment of the most important parameters of denaturation erythrograms at an elevated temperature (58 degrees C), by continuously recording the pH value of a native red blood cell suspension.