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ID PMID Title PublicationDate abstract
24811465 Nasal type extranodal NK/T cell lymphoma diagnosed in a patient with rheumatoid arthritis 2014 Jan Rheumatoid arthritis (RA) patients have increased risk of lymphoma which seems associated mainly with high inflammatory state and disease activity, but also with immunosuppressive agents or Epstein-Barr virus (EBV) infection. Many case reports describe lymphoproliferative lesions arising during methotrexate therapy, often EBV positive with possible regression after methotrexate withdrawal. The authors report the case of an 85-year-old patient with erosive and seronegative RA, in remission under methotrexate who developed a midfacial destructive lesion with epistaxis and local inflammatory signs. The magnetic resonance imaging showed a large nasal septum defect. Anti-neutrophil cytoplasmic antibodies titres and angiotensin converting enzyme were normal. Biopsies of the lesion identified a NK/ T nasal type lymphoma. EBV latent membrane protein research on the lesion was negative. Polymerase chain reaction analysis of the bone marrow aspirate showed EBV DNA positivity. Withdrawal of methotrexate was performed without tumour regression. The authors described the single case of a patient with RA in stable remission under methotrexate who presented a rare type of lymphoma, a nasal type NK/T. EBV active replication was found in the bone marrow.
25280866 Focal adhesion kinase is required for synovial fibroblast invasion, but not murine inflamm 2014 Oct 4 INTRODUCTION: Synovial fibroblasts invade cartilage and bone, leading to joint destruction in rheumatoid arthritis. However, the mechanisms that regulate synovial fibroblast invasion are not well understood. Focal adhesion kinase (FAK) has been implicated in cellular invasion in several cell types, and FAK inhibitors are in clinical trials for cancer treatment. Little is known about the role of FAK in inflammatory arthritis, but, given its expression in synovial tissue, its known role in invasion in other cells and the potential clinical availability of FAK inhibitors, it is important to determine if FAK contributes to synovial fibroblast invasion and inflammatory arthritis. METHODS: After treatment with FAK inhibitors, invasiveness of human rheumatoid synovial fibroblasts was determined with Matrigel invasion chambers. Migration and focal matrix degradation, two components of cellular invasion, were assessed in FAK-inhibited rheumatoid synovial fibroblasts by transwell assay and microscopic examination of fluorescent gelatin degradation, respectively. Using mice with tumor necrosis factor α (TNFα)-induced arthritis in which fak could be inducibly deleted, invasion and migration by FAK-deficient murine arthritic synovial fibroblasts were determined as described above and arthritis was clinically and pathologically scored in FAK-deficient mice. RESULTS: Inhibition of FAK in human rheumatoid synovial fibroblasts impaired cellular invasion and migration. Focal matrix degradation occurred both centrally and at focal adhesions, the latter being a novel site for matrix degradation in synovial fibroblasts, but degradation was unaltered with FAK inhibitors. Loss of FAK reduced invasion in murine arthritic synovial fibroblasts, but not migration or TNFα-induced arthritis severity and joint erosions. CONCLUSIONS: FAK inhibitors reduce synovial fibroblast invasion and migration, but synovial fibroblast migration and TNFα-induced arthritis do not rely on FAK itself. Thus, inhibition of FAK alone is unlikely to be sufficient to treat inflammatory arthritis, but current drugs that inhibit FAK may inhibit multiple factors, which could increase their efficacy in rheumatoid arthritis.
23268367 Tabalumab, an anti-BAFF monoclonal antibody, in patients with active rheumatoid arthritis 2013 Sep 1 OBJECTIVE: To evaluate the efficacy and safety of tabalumab, a monoclonal antibody that neutralises membrane-bound and soluble B-cell activating factor (BAFF), in patients with active rheumatoid arthritis (RA) who showed inadequate response to tumour necrosis factor (TNF) inhibitors. METHODS: Patients on stable methotrexate and with inadequate response to one or more TNF inhibitors were randomised to placebo (n=35), 30 mg tabalumab (n=35) or 80 mg tabalumab (n=30) given intravenously at 0, 3 and 6 weeks. The primary outcome was the proportion of patients achieving an American College of Rheumatology 50% response (ACR50) at week 16 (all tabalumab-treated patients vs placebo). RESULTS: At week 16, no significant differences were observed in the combined tabalumab group versus placebo in ACR50 (12.7% vs 2.9%, p=0.101) or ACR20 response rates (27.0% vs 17.1%, p=0.198). However, significant differences between the combined tabalumab group and placebo were observed at earlier time points for ACR20, ACR50 and Disease Activity Score in 28 joints (DAS28)-C-reactive protein (CRP) reduction. Treatment-emergent adverse events (AEs) were similar with 30 mg tabalumab (65.7%), 80 mg tabalumab (76.7%) and placebo (71.4%), although certain events occurred more often with tabalumab than placebo (eg, infection, anaemia and gastrointestinal events). Serious AEs occurred in two (6.7%) patients receiving 80 mg tabalumab and three (8.6%) receiving placebo, with one serious infection in the placebo group. Initial increases in total and mature B cells were followed by progressive decreases, despite declines in serum tabalumab. CONCLUSIONS: At week 16, the primary end point was not achieved, but an indication of efficacy was observed at earlier time points. Safety findings for tabalumab were consistent with other biological RA therapies. CLINICAL TRIAL REGISTRATION NUMBER: NCT00689728.
23370857 The PTPN22 C1858T polymorphism and rheumatoid arthritis: a meta-analysis. 2013 Aug The aim of this study was to determine whether the protein tyrosine phosphatase nonreceptor 22 (PTPN22) C1858T polymorphism confers susceptibility to rheumatoid arthritis (RA) in populations with different ethnicities. MEDLINE database and manual search were utilized to identify articles in which the PTPN22 polymorphism was determined in RA patients and controls. A meta-analysis was conducted on the associations between the PTPN22 C1858T polymorphism and RA using (1) allelic contrast and (2) dominant model. A total of 30 separate comparisons involving 17,961 RA patients and 18,611 controls were considered in this meta-analysis. Meta-analysis showed an association between the T allele and RA in all subjects (OR = 1.490, 95% CI = 1.332-1.668, P < 1.0 × 10(-9)). After stratification by ethnicity, analysis indicated that the T allele was significantly associated with RA in Europeans and in Non-Europeans (OR = 1.423, 95% CI = 1.260-1.605, P = 1.0 × 10(-8); OR = 1.902, 95% CI = 1.488-2.430, P = 2.8 × 10(-8)). Meta-analysis of the CT + TT genotype showed the same result patterns as that shown by the PTPN22 C1858T polymorphism T allele. Furthermore, a direct comparison between rheumatoid factor (RF)-positive and RF-negative subjects revealed a significant association with the T allele in RA patients with RF, but not in subjects without RF (OR = 1.561, 95% CI = 1.373-1.775, P < 1.0 × 10(-9)). This meta-analysis confirms that the PTPN22 C1858T polymorphism is associated with RA susceptibility in different ethnic groups, especially in Europeans, and the PTPN22 C1858T polymorphism T allele is significantly more prevalent in RF-positive patents than in RF-negative patients.
25227660 Static and dynamic CT imaging of the cervical spine in patients with rheumatoid arthritis. 2015 Feb OBJECTIVE: To compare CR with CT (static and dynamic) to evaluate upper spine instability and to determine if CT in flexion adds value compared to MR imaging in neutral position to assess compression of the subarachnoid space and of the spinal cord. MATERIALS AND METHODS: Twenty-one consecutive patients with atlantoaxial subluxation due to rheumatoid arthritis planned for atlantoaxial fusion were included. CT and MRI were performed with the neck in the neutral position and CT also in flexion. CR in neutral position and flexion were obtained in all patients except for one subject who underwent examination in flexion and extension. RESULTS: CR and CT measurements of atlantoaxial subluxation correlated but were larger by CR than CT in flexion, however, the degree of vertical dislocation was similar with both techniques irrespective of the position of the neck. Cervical motion was larger at CR than at CT. The spinal cord compression was significantly worse at CT obtained in the flexed position as compared to MR imaging in the neutral position. CONCLUSIONS: Functional CR remains the primary imaging method but CT in the flexed position might be useful in the preoperative imaging work-up, as subarachnoid space involvement may be an indicator for the development of neurologic dysfunction.
25527718 RORγt-specific transcriptional interactomic inhibition suppresses autoimmunity associated 2014 Dec 30 The nuclear hormone receptor retinoic acid-related orphan receptor gamma t (RORγt) is a transcription factor (TF) specific to TH17 cells that produce interleukin (IL)-17 and have been implicated in a wide range of autoimmunity. Here, we developed a novel therapeutic strategy to modulate the functions of RORγt using cell-transducible form of transcription modulation domain of RORγt (tRORγt-TMD), which can be delivered effectively into the nucleus of cells and into the central nerve system (CNS). tRORγt-TMD specifically inhibited TH17-related cytokines induced by RORγt, thereby suppressing the differentiation of naïve T cells into TH17, but not into TH1, TH2, or Treg cells. tRORγt-TMD injected into experimental autoimmune encephalomyelitis (EAE) animal model can be delivered effectively in the splenic CD4(+) T cells and spinal cord-infiltrating CD4(+) T cells, and suppress the functions of TH17 cells. The clinical severity and incidence of EAE were ameliorated by tRORγt-TMD in preventive and therapeutic manner, and significant reduction of both infiltrating CD4(+) IL-17(+) T cells and inflammatory cells into the CNS was observed. As a result, the number of spinal cord demyelination was also reduced after tRORγt-TMD treatment. With the same proof of concept, tTbet-TMD specifically blocking TH1 differentiation improved the clinical incidence of rheumatoid arthritis (RA). Therefore, tRORγt-TMD and tTbet-TMD can be novel therapeutic reagents with the natural specificity for the treatment of inflammatory diseases associated with TH17 or TH1. This strategy can be applied to treat various diseases where a specific transcription factor has a key role in pathogenesis.
25288220 Targeting the P2X7 receptor in rheumatoid arthritis: biological rationale for P2X7 antagon 2014 Nov OBJECTIVES: This paper aims to explore the functional significance of the P2X7 receptor in preclinical models of rheumatoid arthritis. METHODS: Preclinical studies in vivo were performed using the rat streptococcal cell wall (SCW) arthritis model. Ex vivo cultures of lipopolysaccharide (LPS)/benzoylbenzoyl adenosine triphosphate (BzATP)-stimulated human monocytes were generated to test the activities of a novel, highly specific inhibitor of human P2X7, AZD9056, on interleukin (IL)-1 and IL-18 release. RESULTS: P2X7 receptor expression was detected in inflamed synovial tissue after onset of SCW-induced arthritis in rats. Inhibition of P2X7 therein led to reduced articular inflammation and erosive progression. No effect was noted on acute-phase responses. Ex vivo, AZD9056 inhibited IL-1 and IL-18 release to BzATP in LPS-primed human monocytes. CONCLUSIONS: P2X7 receptor inhibition could represent a novel approach to the treatment of inflammatory arthritis. However, confirmatory clinical studies are warranted to further explore this possibility.
24886513 Synovial explant inflammatory mediator production corresponds to rheumatoid arthritis imag 2014 May 5 INTRODUCTION: Despite the widespread use of magnetic resonance imaging (MRI) and Doppler ultrasound for the detection of rheumatoid arthritis (RA) disease activity, little is known regarding the association of imaging-detected activity and synovial pathology. The purpose of this study was to compare site-specific release of inflammatory mediators and evaluate the corresponding anatomical sites by examining colour Doppler ultrasound (CDUS) and MRI scans. METHODS: RA patients were evaluated on the basis of CDUS and 3-T MRI scans and subsequently underwent synovectomy using a needle arthroscopic procedure of the hand joints. The synovial tissue specimens were incubated for 72 hours, and spontaneous release of monocyte chemoattractant protein 1 (MCP-1), interleukin 6 (IL-6), macrophage inflammatory protein 1β (MIP-1β) and IL-8 was measured by performing multiplex immunoassays. Bone marrow oedema (BME), synovitis and erosion scores were estimated on the basis of the rheumatoid arthritis magnetic resonance imaging score (RAMRIS). Mixed models were used for the statistical analyses. Parsimony was achieved by omitting covariates with P > 0.1 from the statistical model. RESULTS: Tissue samples from 58 synovial sites were obtained from 25 patients. MCP-1 was associated with CDUS activity (P = 0.009, approximate Spearman's ρ = 0.41), RAMRIS BME score (P = 0.01, approximate Spearman's ρ = 0.42) and RAMRIS erosion score (P = 0.03, approximate Spearman's ρ = 0.31). IL-6 was associated with RAMRIS synovitis score (P = 0.04, approximate Spearman's ρ = 0.50), BME score (P = 0.04, approximate Spearman's ρ = 0.31) and RAMRIS erosion score (P = 0.03, approximate Spearman's ρ = 0.35). MIP-1β was associated with CDUS activity (P = 0.02, approximate Spearman's ρ = 0.38) and RAMRIS synovitis scores (P = 0.02, approximate Spearman's ρ = 0.63). IL-8 associations with imaging outcome measures did not reach statistical significance. CONCLUSIONS: The association between imaging activity and synovial inflammatory mediators underscores the high sensitivity of CDUS and MRI in the evaluation of RA disease activity. The associations found in our present study have different implications for synovial mediator releases and corresponding imaging signs. For example, MCP-1 and IL-6 were associated with both general inflammation and bone destruction, in contrast to MIP-1β, which was involved solely in general synovitis. The lack of association of IL-8 with synovitis was likely underestimated because of a large proportion of samples above assay detection limits among the patients with the highest synovitis scores.
22638733 Association between the chemokine receptor 5 delta32 polymorphism and rheumatoid arthritis 2013 Mar OBJECTIVE: The aim of this study was to determine whether the functional chemokine receptor 5 delta32 (CCR5-Δ32) polymorphism confers susceptibility to rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA). METHODS: Meta-analysis was conducted on associations between the CCR5-Δ32 polymorphism and RA and JIA using (1) allele contrast and (2) the recessive, (3) the dominant, and (4) the additive models. RESULTS: Eleven population comparisons based on the data obtained from nine studies involving 13,412 subjects (RA 3,848, controls 4,095; JIA 1,599, controls 3,870) were considered. In all study subjects, meta-analysis showed a significant negative association between RA and the CCR5-Δ32 allele (OR = 0.771, 95 % CI = 0.694-0.866, p = 6.5 × 10(-7)). Stratification by ethnicity indicated a significant association between the CCR5-Δ32 allele and RA in Europeans (OR = 0.8001, 95 % CI = 0.709-0.904, p = 3.2 × 10(-5)). Meta-analysis showed associations between the CCR5-Δ32 allele and JIA in Europeans and oligoarticular type (OR = 0.797, 95 % CI = 0.690-0.921, p = 0.002; OR = 0.475, 95 % CI = 0.352-0.693, p = 9.5 × 10(-8)). CONCLUSIONS: This meta-analysis demonstrates that the CCR5-Δ32 polymorphism may confer susceptibility to RA and JIA in Europeans, and suggests that the CCR5-Δ32 allele protects against the development of RA and JIA.
24656309 Short-term results of the PROSNAP linked elbow prosthesis with a snap-in structure and mod 2014 Jun BACKGROUND: We aimed to evaluate the early clinical results of the reconstruction of problematic elbow joints due to rheumatoid arthritis (RA) using a PROSNAP linked elbow prosthesis (Kyocera Medical, Osaka, Japan) for total elbow arthroplasty. METHODS: Seventeen elbows in 14 RA patients were replaced with a PROSNAP elbow with cement fixation. The patients comprised 1 man and 13 women, with a mean age of 63.9 years (range, 52-83 years) at the time of surgery. The preoperative conditions of the elbows were arthritis mutilans (n = 10), an ankylosed or stiff elbow with a preoperative range of motion of 45° or less (n = 4), and loosening of a primary total elbow arthroplasty (n = 3). The mean follow-up period was 47.7 months (range, 32-69 months), with a 100% follow-up rate. The clinical outcome of the elbows was evaluated by the Mayo Elbow Performance Index (maximum, 100 points). RESULTS: The mean postoperative Mayo Elbow Performance Index score improved from 57.6 points to 97.1 points. Preoperatively, 3 of the 17 elbows were judged as good, 7 as fair, and 7 as poor; at final follow-up, 16 elbows were judged as excellent and 1 as good. Complications were noted in 1 elbow (6%), which had undergone a postoperative fracture. CONCLUSIONS: The PROSNAP elbow prosthesis can be safely implanted through a relatively easy procedure and provides satisfactory short-term clinical outcomes for the reconstruction of severely damaged RA elbows. LEVEL OF EVIDENCE: Level IV, case series, treatment study.
24184038 Clinical significance of autoantibodies to the pericentromeric heterochromatin protein 1a 2013 Dec OBJECTIVE: The objective of the study is to determine the frequency and the clinical significance of autoantibodies to the pericentromeric heterochromatin protein 1 (HP1). So far this antinuclear antibody specificity has been mainly reported in patients with the CREST syndrome. METHODS: We screened the sera of 199 individuals, including patients suffering from various autoimmune disorders (Group I, n=145) and non autoimmune diseases (Group II, n=44 patients) as well as healthy individuals (Group III, n=30). The sera were systematically tested by Western blot and ELISA using a GST-HP1α fusion protein as an antigen. RESULTS: Anti-HP1 antibodies were detected in 32% of patients in Group I, 11.3% in Group II and 3.3% of individuals in Group III. They could be detected in sera containing or not antinuclear antibodies detectable by indirect immunofluorescence. Anti-HP1 antibodies were mostly associated with the CREST and Sjogren's syndromes (70% and 44.4%, respectively). They could also be detected in 22.2% of patients suffering from various other autoimmune diseases. However, their negative predictive value was 94% in the CREST syndrome. CONCLUSION: Anti-HP1 autoantibodies are associated with a large spectrum of disorders. However, they have a diagnostic value in the CREST syndrome.
22661643 Genetic and environmental determinants for disease risk in subsets of rheumatoid arthritis 2013 May OBJECTIVES: To increase understanding of the aetiology and pathogenesis of rheumatoid arthritis (RA), genetic and environmental risk factors for RA subsets, defined by the presence or absence of different anticitrullinated protein/peptide antibodies (ACPAs) targeting citrullinated peptides from α-enolase, vimentin, fibrinogen and collagen type II, were investigated. METHODS: 1985 patients with RA and 2252 matched controls from the EIRA case-control cohort were used in the study. Serum samples were assayed by ELISA for the presence of anticyclic citrullinated peptides (anti-CCP) antibodies and four different ACPA fine specificities. Cross-reactivity between ACPAs was examined by peptide absorption experiments. Genotyping was performed for HLA-DRB1 shared epitope (SE) alleles and the PTPN22 gene, while information regarding smoking was obtained by questionnaire. The association of genetic and environmental risk factors with different subsets of RA was calculated by logistic regression analysis. RESULTS: Limited cross-reactivity was observed between different ACPA fine specificities. In total, 17 RA subsets could be identified based on their different ACPA fine specificity profiles. Large differences in association with genetic and environmental determinants were observed between subsets. The strongest association of HLA-DRB1 SE, PTPN22 and smoking was identified for the RA subset which was defined by the presence of antibodies to citrullinated α-enolase and vimentin. CONCLUSION: This study provides the most comprehensive picture to date of how HLA-DRB1 SE, PTPN22 and smoking are associated with the presence of specific ACPA reactivities rather than anti-CCP levels. The new data will form a basis for molecular studies aimed at understanding disease development in serologically distinct subsets of RA.
23384023 Etanercept-induced Wegener granulomatosis in a patient with rheumatoid arthritis. 2013 Jan A very rare case of etanercept-induced Wegener's granulomatosis in a patient with long-standing rheumatoid arthritis is reported. A thorough critical analysis on Wegener's granulomatosis pathogenetic mechanisms is done. The peculiarities of etanercept pharmacodynamic features are also presented together with some suggestions of possible induction pathways.
24191905 Renal cell carcinoma in a patient with rheumatoid arthritis treated with adalimumab. 2014 Mar Rheumatoid arthritis (RA) is a chronic erosive inflammatory disease which can involve the locomotor system and cause systemic involvement. The efficacy and safety of anti-TNF-alpha drugs have been shown in active RA cases that are resistant to traditional disease-modifying antirheumatic drugs. However, it is well known that anti-TNF-alpha drugs may cause lymphomas and various solid malignancies. On the other hand, there are studies on the efficacy of anti- TNF-alpha drugs in the treatment of resistant renal cell cancer. This case report presents a 57-year-old female patient with hematuria who had been followed up with the diagnosis of RA for 20 years and had been using adalimumab for the last 4 years. A solid mass was found in the left kidney in the abdominal ultrasonography and computed tomography. Nephrectomy was performed by general surgery. Histopathological findings of the specimen were consistent with renal cell carcinoma.
25218914 Comprehensive review of genetic association studies and meta-analysis on miRNA polymorphis 2016 Jan BACKGROUND: MicroRNAs (miRNAs), small RNA molecules, play a role in the development and differentiation of immune cells in both innate and adaptive immune responses. Our study was aimed to investigate the association between three miRNA polymorphism and rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) by using meta-analysis approach. METHODS: A PubMed database search was conducted during August 2013 to identify case-control studies of miRNAs and RA or SLE risk. Two authors independently extracted information on the study design, the characteristics of the study participants, exposure and outcome assessments. The fix-effects and random-effects models were used for the risk estimates by Stata 11.0 software. RESULTS: Our meta-analysis of six case-control studies involving a total of 998 RA cases and 1493 controls identified no significant association between mir-146a rs2910164 and RA, with an overall OR of 0.843 (95% CI=0.642-1.105; CC vs. GG). No association was observed in three studies with a total of 1532 cases and 2168 controls between miR-146a rs2910164 and SLE risk (OR=0.911, 95% CI=0.710-1.171; CC vs. GG). Three studies with a total of 529 cases and 595 controls evaluated the mir-499 rs3746444 polymorphism and its association with RA. There was a decreased overall risk of RA under the allelic and genotypic models [OR=0.616, 95% CI=0.384-0.981, (T vs. C allele) and OR=0.386, 95% CI=0.226-0.659, (TT vs. CC)]. Two studies with 4826 cases and 4181 controls evaluated miR-146a rs57095329 and its association with SLE. There was a significant association between miR-146a rs57095329 and SLE (OR=1.263, 95% CI=1.136-1.405, G vs. A allele). CONCLUSIONS: The present meta-analysis suggests important roles for the mir-499 rs3746444 polymorphism in RA, especially in the Caucasian population and for miR-146a rs57095329 polymorphism in SLE. Further studies with large sample size are needed to confirm these associations.
24641111 The expanding role of IL-7 and thymic stromal lymphopoietin as therapeutic target for rheu 2014 May INTRODUCTION: The discovery of IL-7 and thymic stromal lymphopoietin (TSLP) has been a major step in the understanding of arthritis. IL-7 amplifies the inflammation induced by other cytokines, primarily TNF. In animal models of arthritis, inhibition of IL-7 limits inflammation and joint erosion. TSLP is an IL-7-like cytokine that triggers dendritic cell-mediated Th2-type inflammatory responses and is considered as a master switch for allergic inflammation. TSLP is a downstream molecule of TNF-α and as such may be involved in the pathophysiology of inflammatory arthritis. AREAS COVERED: This review summarizes current knowledge of the role of IL-7 and TSLP derived from both animal models and studies in patients with rheumatoid arthritis (RA). The emergence of IL-7 blockade as a future therapy in RA is highlighted, along with the potential goals and limitations of this therapeutic approach. The write-up also highlights the functional capacities of TSLP in arthritis. EXPERT OPINION: Evidences suggest important roles for IL-7 and TSLP in the pathogenesis of RA and can be viewed as potential therapeutic targets. Regulation of these at genetic level is a promising investigational area. Given the difficulty in reconstituting T cells in patients with RA, therapeutic approaches that minimize the elimination of T cells are likely to be more desirable.
24345416 Prevalence of methotrexate intolerance in rheumatoid arthritis and psoriatic arthritis. 2013 INTRODUCTION: The aim of this study was to determine the prevalence of gastrointestinal and behavioural symptoms occurring before (anticipatory/associative) and after methotrexate (MTX) administration, termed MTX intolerance, in rheumatoid (RA) and psoriatic arthritis (PsA). METHODS: Methotrexate Intolerance Severity Score (MISS), previously validated in juvenile idiopathic arthritis patients, was used to determine MTX intolerance prevalence in 291 RA/PsA patients. The MISS consisted of four domains: abdominal pain, nausea, vomiting and behavioural symptoms, occurring upon, prior to (anticipatory) and when thinking of MTX (associative). MTX intolerance was defined as ≥6 on the MISS with ≥1 point on anticipatory and/or associative and/or behavioural items. RESULTS: A total of 123 patients (42.3%) experienced at least one gastrointestinal adverse effect. The prevalence of MTX intolerance was 11%. MTX intolerance prevalence was higher in patients on parenteral (20.6%) than on oral MTX (6.2%) (p < 0.001). CONCLUSION: Besides well-known gastrointestinal symptoms after MTX, RA and PsA patients experienced these symptoms also before MTX intake. RA and PsA patients on MTX should be closely monitored with the MISS for early detection of MTX intolerance, in order to intervene timely and avoid discontinuation of an effective treatment.
24665079 Citrulline-specific Th1 cells are increased in rheumatoid arthritis and their frequency is 2014 Jul OBJECTIVE: Rheumatoid arthritis (RA) is thought to be a T cell-mediated disease, based on its strong association with HLA class II alleles, clinical responsiveness to T cell-directed therapies, and the presence of CD4+ T cells in rheumatoid joints. The presence of anti-citrullinated protein antibodies (ACPAs) in RA serum and the association of these antibodies with HLA-DR4 alleles implicate citrulline-specific autoreactive T cells in the development and progression of RA. The goal of this study was to determine the characteristics and specificity of autoreactive T cell responses in RA. METHODS: We developed a panel of HLA-DRB1*04:01 tetramers, selecting citrullinated peptides from synovial antigens and verifying their immunogenicity in DRB1*04:01-transgenic mice. Seven tetramers were used to examine the ex vivo frequency and surface phenotype of citrulline-specific (Cit-specific) T cells in patients with RA and healthy subjects with DRB1*04:01 haplotypes, using a magnetic enrichment procedure. RESULTS: Cit-specific T cells were detectable in peripheral blood samples from both healthy subjects and RA patients. In comparison to healthy subjects, RA patients had significantly higher frequencies of Cit-specific T cells, and a greater proportion of these cells displayed a Th1 memory phenotype. Among RA patients, the frequency of Cit-specific T cells was highest within the first 5 years after diagnosis of RA and was decreased in patients taking biologic agents, irrespective of disease duration. CONCLUSION: These findings link the presence of ACPAs in RA with Th1 cells specific for citrullinated epitopes and provide tools for disease-specific immunomonitoring of autoreactive T cells.
25279654 Endoscopic transnasal odontoidectomy without resection of nasal turbinates: clinical outco 2014 Dec Object The goal of the study was to report a series of consecutive patients who underwent endoscopic transnasal odontoidectomy (ETO) without resection of nasal turbinates. The techniques for this minimally invasive approach are described in detail. Methods The authors conducted a retrospective review of consecutive patients who underwent ETO for basilar invagination. All the patients had myelopathy caused by compression at the cervicomedullary junction, which required surgical decompression. Preoperative and postoperative data, including those from radiographic and clinical evaluations, were compared. Morbidity and mortality rates for the procedure are also reported in detail. Results Thirteen patients (6 men and 7 women) with a mean age of 52.7 years (range 24-72 years) were enrolled. The basilar invagination etiologies were rheumatoid arthritis (n = 5), trauma (n = 4), os odontoideum (n = 2), ankylosing spondylitis (n = 1), and postinfectious deformity (n = 1). The average follow-up duration was 51.2 months (range 0.3-105 months). One patient died 10 days after the operation as a result of meningitis caused by CSF leakage. Among the other 12 patients, the average postoperative Nurick grade (3.2) was significantly improved over that before the operation (4.1, p = 0.004). The mean (± SD) duration of postoperative intubation was 1.5 ± 2.1 days, and there was no need for perioperative tracheostomy or nasogastric tube feeding. There also was no postoperative velopharyngeal insufficiency. There were 6 (46%) intraoperative and 2 (15%) postoperative CSF leaks in the 13 patients in this series. Conclusions ETO is a viable and effective option for decompression at the ventral cervicomedullary junction. This approach is minimally invasive and causes little velopharyngeal insufficiency. The pitfall of this approach is the difficulty in repairing dural defects and subsequent CSF leakage.
23290888 The impact of genes on the occurrence of autoantibodies in rheumatoid arthritis. A study o 2013 Mar OBJECTIVE: To assess the genetic effect on the occurrence of rheumatoid arthritis (RA) associated autoantibodies. METHODS: A co-twin control study of 27 monozygotic (MZ) and 51 dizygotic same sexed (DZss) RA discordant twins. OUTCOME MEASURES: The probandwise concordance rate of anti-keratin antibodies (AKA), anti-cyclic citrullinated peptide antibodies (ACPA), IgA- and IgM rheumatoid factor (IgA-RF and IgM-RF). The odds ratio for these autoantibodies based on both conditional and unconditional logistic regression adjusting for the two major genetic risk factors as well as smoking. RESULTS: The probandwise concordance rates (95% CI) of ACPA, AKA, IgM-RF and IgA-RF were 78.6 (55.4-92.4), 16.7 (0.6-58.4), 30.0 (7.3-60.6), 42.1 (14.5-71.1) in MZ twins and 25.0 (10.3-44.4), 0.0 (0.0-27.7), 10.5 (1.4-31.5) and 22.2 (6.8-45.0) in DZss twins. In twin pairs discordant for both RA and autoantibodies the OR of ACPA, AKA, IgM-RF and IgA-RF was 5 (0.5-236.5) 9 (1.3-394.5) 272 (3.5-593.2) and 10 (1.4-434.0) in MZ twin pairs and 17 (4.4-146.1) 20 (3.2-828.0) 33 (5.5-1342.4) and 577 (7.4-1149.2) in DZss twin pairs. In multiple logistic regression analysis on ACPA, the MZ/DZ OR was 21.1 (3.3-213.5) when adjusting for age, sex, ever smoking, PTPN22 1858 T-allele, Shared Epitope (SE) and SE-smoking interaction. CONCLUSION: There is a genetic contribution to ACPA generation independent of both SE and PTPN22 1858 T-allele. Environmental factors may trigger the expression of IgA-RF, ACPA and AKA in healthy persons who are predisposed to RA.