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ID PMID Title PublicationDate abstract
29119259 Rheumatoid Arthritis-Associated Interstitial Lung Disease: Current Concepts. 2017 Nov 9 PURPOSE OF REVIEW: Among the many extra-articular complications of rheumatoid arthritis (RA), interstitial lung disease (ILD) contributes significantly to morbidity and mortality. Prevalence estimates for RA-ILD vary widely depending on the specific clinical, radiographic, and functional criteria used to establish the diagnosis. A key unresolved issue is whether early, subclinical forms of RA-ILD represent a precursor to end stage, fibrotic lung disease. Based on uncertainties surrounding the natural history of RA-ILD, incomplete understanding of underlying disease pathogenesis, and lack of controlled clinical trials, evidence-based therapeutic strategies remain largely undefined. RECENT FINDINGS: Correlative clinico-epidemiological studies have identified key risk factors for disease progression. Complementing these findings, the identification of specific molecular and serological markers of RA-ILD has improved our understanding of disease pathogenesis and established the foundation for predictive biomarker profiling. Experience from case series and cohort studies suggests that newer biological agents such as rituximab may be viable treatment options. RA-ILD continues to have a major impact on "disease intrinsic" morbidity and mortality. Increased understanding of disease pathogenesis and the natural history of subclinical RA-ILD will promote the development of more refined therapeutic strategies.
28545554 Whipple's disease mimicking rheumatoid arthritis can cause misdiagnosis and treatment fail 2017 May 25 BACKGROUND: Whipple's disease, a rare chronic infectious disorder caused by Tropheryma whipplei, may present with predominant joint manifestations mimicking rheumatoid arthritis (RA). METHODS: A retrospective single-center cohort study of seven patients was performed. Clinical symptoms were assessed by review of medical charts and Whipple's disease was diagnosed by periodic-acid-Schiff-stain and/or Tropheryma whipplei-specific polymerase-chain-reaction. RESULTS: Median age at disease onset was 54 years, six patients were male. Median time to diagnosis was 5 years. All patients presented with polyarthritis with a predominantly symmetric pattern. Three had erosive arthritis. Affected joints were: wrists (5/7), metacarpophalangeal joints (MCPs) (5/7), knees (5/7), proximal interphalangeal joints (PIPs) (3/7), hips (2/7), elbow (2/7), shoulder (2/7). All patients had increased C-reactive-protein concentrations, while rheumatoid factor and anti-CCP-antibodies were absent, and were initially (mis)classified as RA-patients according to EULAR/ACR-criteria (median DAS28 4.3). Six patients received antirheumatic treatment consisting of prednisone with methotrexate and/or leflunomide, three were additionally treated with at least one biologic agent (abatacept, adalimumab, etanercept, rituximab, tocilizumab). Most patients showed insufficient treatment response. In all patients Tropheryma whipplei was detected in synovial fluid by polymerase-chain-reaction; in three patients the diagnosis of Whipple's disease was further ascertained by periodic-acid-Schiff-staining. Gastrointestinal symptoms and other extra-articular manifestations were absent, mild or non-specific. Treatment was initiated with trimethoprin/sulfamethoxazole in five and doxycycline/hydroxychloroquine in two patients and had to be adapted in five patients. Finally, all patients had good treatment responses with improvement of arthritis and extra-articular manifestations. CONCLUSION: Whipple's disease is rare and can mimic rheumatoid arthritis. Especially patients with seronegative rheumatoid arthritis with a prolonged disease course and insufficient treatment response should be reevaluated for Whipple's disease.
27749238 Efficacy and safety of down-titration versus continuation strategies of biological disease 2017 Jan OBJECTIVES: To evaluate the efficacy and safety of down-titration (dose reduction/tapering) strategies compared with continuation of biological disease-modifying anti-rheumatic drugs (DMARDs) in patients with rheumatoid arthritis (RA) who achieved and maintained low disease activity or remission. METHODS: We searched the following electronic database up to March 2016: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and conference proceedings of the American College of Rheumatology (ACR) and European League against Rheumatism (EULAR). Our meta-analysis included randomized controlled trials (RCTs) of RA patients with low disease activity or in remission that compared down-titration treatment with continuation treatment. Data on flare, defined as a 28-joint Disease Activity Score of ≥3.2, had to have been reported. Outcomes on efficacy or safety were collected. RESULTS: Of 1136 references identified, five RCTs (total, 771 participants) were included. The incidence of disease relapse in the down-titration and continuation groups was similar (risk ratio (RR)=1.14, 95% CI=0.88-1.49). There was no statistical difference in the number of serious adverse events (RR=1.15, 95% CI=0.53-2.49). Withdrawals due to inefficacy or toxicity were similar between groups and no clinically meaningful difference in efficacy outcomes was observed by continuation treatment. CONCLUSIONS: Our findings indicated that continuing a standard dose of biological DMARDs in patients with low disease activity conveyed no significant benefit as compared with down-titration therapy, suggesting that a down-titration strategy is as effective as a continuation strategy. Since the number of trials meeting the criteria for this meta-analysis was relatively low, future analyses with additional prospective RCTs are required to compare other biological agents and evaluate the long-term efficacy of these two strategies.
28142302 Outcomes of modified metatarsal shortening offset osteotomy for forefoot deformity in pati 2017 Nov OBJECTIVES: Advances in drug therapy for rheumatoid arthritis (RA) have been encouraging us to preserve the metatarsopharangeal (MTP) joint in correction of forefoot deformities, and original metatarsal shortening offset osteotomy was recommended as one of the conventional surgical options for forefoot deformities in RA cases. The objective of this study was to evaluate short- to mid-term outcomes of modified metatarsal shortening offset osteotomy. METHODS: A retrospective observational study was completed for 80 RA cases (mean follow-up period: 3.2 years) who underwent modified metatarsal shortening offset osteotomy. Both lesser toe scales and RA foot ankle scales were administered using the Japanese Society for Surgery of the Foot (JSSF) standard rating system, and a postoperative self-administered foot evaluation questionnaire (SAFE-Q) at final follow-up was also checked to evaluate clinical outcomes. RESULTS: This procedure significantly improved clinical scores of both the JSSF [lesser toes and RA foot and ankle] scales. Of 80 feet, 24 (30%) showed recurrence of MTP joint subluxation/dislocation. Furthermore, the feet in the recurrence group showed significant varus hindfoot. On the other hand, valgus foot in the recurrence group more frequently included midfoot bony ankyloses. All of the affected feet showed the limitation of MTP joints (<70°) after surgery. CONCLUSIONS: Modified metatarsal shortening offset osteotomy was recommended for RA forefoot disorders as one of the joint preservation surgeries in short- to mid-term follow-up. However, some modifications to avoid limitation of ROM in the MTP joint are required. It must be borne in mind that varus hindfoot and/or bony ankyloses in the mid-hindfoot can cause recurrence of dorsal dislocation/subluxation of the lesser toe MTP joint.
28121192 Integrating patients' perceptions into clinical practice guidelines for the management of 2017 Nov OBJECTIVE: Patients' values and preferences are among the key factors that determine the strength of recommendations presented in clinical practice guidelines (CPG). The aim of this study was to summarize the integration process for patients' perceptions into the development of CPG for rheumatoid arthritis (RA) management in Japan. METHODS: We used a mixed-methods approach. Questionnaires that could be self-administered were mailed to 2222 RA patients randomly selected from the Japan Rheumatism Friendship Association (JRFA) membership list that was age- and prefecture-stratified. A focus group with five JRFA executive members was formed to verify the results of the questionnaire. RESULTS: A total of 1470 patients aged 20-79 years old returned the questionnaire. Analysis of the questionnaire data revealed that the topics selected by the CPG task force met the patients' needs. The focus group participants showed reluctance to use the term 'preference' because patients would not want to take any medications but would have to take them out of necessity. CONCLUSIONS: We confirmed that the new CPG successfully addressed clinical issues that were important to both rheumatologists and patients. Clinicians should understand patients' reluctance to take medications and explain the role of each medication well to increase adherence.
29354920 [Effect of heat-reinforcing needling on serum metabolite profiles in rheumatoid arthritis 2017 Sep 12 OBJECTIVE: To explore heat-reinforcing needling for the metabolite profiling changes in serum of rheumatoid arthritis (RA) rabbits with liquid chromatograph-mass spectrometer (LC-MS) technique, and to investigate its mechanisms. METHODS: Forty clean purple blue rabbits were randomized into a normal group, a model group, a reinforcing-reducing needling (RRN) group, a twirling-reinforcing needling (TRN) group, and a heat-reinforcing needling (HRN) group, 8 cases in each group. RA rabbits with cold syndrome were made with ovalbumin and freezing except those in the normal group. No treatment was given in the normal and model groups. The corresponding manipulations for 7 days were applied at "Zusanli" (ST 36) in the three acupuncture groups, 30 min a time, once a day. After intervention the pain threshold and the local skin temperature of each group were observed. Fresh serum from heart was collected for metabonomics detection. Principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) were adopted. Several metabolites were screened by the variable importance in the projection values (VIP>1) and P value (P<0.05). RESULTS: The pain threshold and the local skin temperature in the model group were lower than those in the normal group (both P<0.05). The pain threshold and the local skin temperature in the three acupuncture groups were higher than those in the model group after intervention (all P<0.05), which were better in the HRN group than those in the RRN and TRN groups (all P<0.05). The serum metabolites of carnitine, LysoPC (14∶0), LysoPC (18∶3), LysoPE (0∶0/20∶5), LysoPE (0∶0/22∶1), decylic acid, stearic acid and lactic acid in the model group increased compared with those in the normal group, and other metabolites decreased, including leucine, valine, glutamine, pyroglutamic acid, α-ketoglutaric acid, succinic acid, fumaric acid, malic acid, galactose, mannose. Those metabolites were correlated fatty acid, amino acid, citric acid cycle, and glucose metabolism. The metabolites above-mentioned in the three acupuncture groups were regulated in various degrees (all P<0.05). Lactic acid decreased and succinic acid, fumaric acid, malic acid, galactose, mannose increased more obviously in the HRN group than those in the RRN and TRN groups. CONCLUSION: The specificity of heat-reinforcing needling for RA presents the regulation for citric acid cycle and glucose metabolism.
28177535 Serum bilirubin and the risk of rheumatoid arthritis. 2017 Nov BACKGROUND: Oxidative stress and immune imbalance play an important role in the pathogenesis of rheumatoid arthritis (RA). Bilirubin is a powerful antioxidant and also regarded as immunomodulator. Increased evidence shows that bilirubin should be a protective factor for autoimmune disease. However, the relationship between bilirubin and RA remain unclear. METHODS: We analyzed serum bilirubin levels and other laboratory and clinical data in 130 RA patients (35 patients without any complications), 81 osteoarthritis (OA) patients and 96 healthy controls. RESULTS: Binary logistic regression adjusted by age and gender revealed that the levels of serum total, indirect bilirubin were significantly lower in RA patients, when compared with healthy controls (P=.015, OR=0.767, 95% CI=0.619-0.951; P=.010, OR=0.664, 95% CI=0.487-0.906, respectively) or OA patients (P=.000, OR=0.763, 95% CI=0.661-0.882; P=.000, OR=0.656, 95% CI=0.532-0.808, respectively). A reduced trend of levels of bilirubin has been detected along with increased disease activity, despite with no significance (P>.05). Spearman rank test further demonstrated that IgG and ESR were negative associated with total, indirect bilirubin, and albumin, prealbumin, APOA, HDL-C were positively associated with bilirubin. CONCLUSIONS: In conclusion, the levels of serum bilirubins were decreased in RA, and decreased levels could be associated with IgG, albumin and inflammatory marker ESR.
27423206 Associations of methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms 2017 Feb The aim of our study was to conduct a meta-analysis to assess whether combined evidence shows associations between C677T and A1298C polymorphisms of methylenetetrahydrofolate reductase (MTHFR) and genetic susceptibility to rheumatoid arthritis (RA). A total of 11 articles involving 20 comparisons were included, containing 12 comparisons for the MTHFR C677T polymorphism and 8 comparisons for the MTHFR A1298C polymorphism. Significant evidence was detected for the association of RA susceptibility with the MTHFR C677T polymorphism T allele under allelic contrast and dominant model in Asians (T versus C, OR = 1.300, 95 % CI = 1.104-1.531, p = 0.002; TT + CT versus CC, OR = 1.495, 95 % CI = 1.187-1.882, p = 0.001). Significant association between RA susceptibility and the MTHFR A1298C polymorphism A allele under recessive model was found in the overall meta-analysis (AA versus AC + CC, OR = 1.281, 95 % CI = 1.048-1.565, p = 0.016). Our meta-analysis results demonstrate that the MTHFR C677T polymorphism is involved in the genetic susceptibility of RA in Asians, and the MTHFR A1298C polymorphism is associated with genetic susceptibility to RA in the overall population. Given the paucity of studies, especially in non-Asian populations, further studies with larger sample sizes are required to elucidate the role of MTHFR polymorphisms in the genetic basis of RA in different ethnic populations.
27796618 Distinct Secretory Activity and Clinical Impact of Subcutaneous Abdominal Adipose Tissue i 2017 Feb In the general population, low-grade inflammation of adipose tissue accompanies obesity and contributes to cardiovascular disease (CVD) development, but the implication of this tissue in rheumatic disease pathology is unclear. Therefore, we characterized the secretory activity of subcutaneous abdominal adipose tissue (SAAT) of females with rheumatoid arthritis (RA) and osteoarthritis (OA) and searched for its relationship with intensity of systemic inflammation, body composition and comorbidity. The secretion of classical adipokines (leptin, adiponectin), pro- and anti-inflammatory factors, i.e. interleukin (IL)-6, IL-8, IL-10, tumour necrosis factor (TNF), macrophage migration inhibitory factor (MIF) and hepatocyte growth factor (HGF), from SAAT explants was measured by specific enzyme-linked immunosorbent assays. Patients' body composition was evaluated by bioelectric impendence technique. Rheumatoid SAAT secreted more adiponectin, IL-6, IL-10, TNF and MIF but less leptin than respective osteoarthritis tissues. In RA patients, TNF secretion correlated with cachectic body composition, HGF release was linked to secondary amyloidosis and visceral fat rating was an independent risk factor for CVD. In OA, secretion of leptin and HGF positively, while adiponectin inversely, correlated with systemic inflammation markers, and the release of MIF was an independent risk factor for CVD. This study reveals differences between RA and OA patients in SAAT secretory activity and suggests its different clinical impact in these diseases, characterized by high- and low-grade systemic inflammation, respectively. In RA, SAAT may directly or via an effect on body composition contribute to amyloidosis, cachexia or CVD co-occurring, while in OA SAAT-derived adipocytokines may rather regulate intensity of systemic inflammation and redound to CVD emergence.
28375890 Ratio of Range of Motion of the Ankle and Surrounding Joints After Total Ankle Replacement 2017 Apr 5 BACKGROUND: This study attempted to identify where motion occurs after total ankle replacement, the difference in range-of-motion contributions between fixed-bearing and mobile-bearing total ankle replacements, and the contribution of abnormal peritalar motion. We hypothesized that sagittal plane radiographic assessment would demonstrate that actual ankle motion through the prosthesis is less than the total arc of ankle motion that may be observed clinically secondary to contributions from adjacent joints. METHODS: Patients underwent routine standardized weight-bearing maximum dorsiflexion and plantar flexion sagittal radiographs. Sagittal plane ankle and foot measurements were performed on each dorsiflexion and plantar flexion radiograph to determine the total arc of ankle motion, actual ankle motion through the prosthesis, motion through the subtalar and talonavicular joints, and midfoot motion. Motion radiographs were routinely made at 1 year postoperatively and at the time of the most recent follow-up. A minimum follow-up of 2 years was required of all patients. RESULTS: There were 197 patients who met the inclusion criteria (75 INBONE, 52 Salto Talaris, and 70 STAR prostheses). The mean time to the latest radiographs (and standard deviation) was 42.9 ± 18.8 months. The mean actual ankle motion through the prosthesis was 25.9° ± 12.2°, which was significantly less (p < 0.001) than the mean total motion arc of 37.6° ± 12.0°. The motion of the ankle accounted for 68% of total range of motion, and motion of the peritalar joints accounted for 32%. There was no significant difference (p > 0.05) among the 3 prostheses or when comparing fixed and mobile-bearing designs for both ranges of motion. CONCLUSIONS: This study demonstrates that actual ankle motion after total ankle replacement is approximately 12° less than the total arc of motion that might be observed clinically because of increased midfoot and subtalar motion. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
29197380 A time-course microarray data analysis reveals consistent dysregulated genes and upstream 2017 Dec 2 BACKGROUND: The purpose of this study is to identify key genes and microRNAs (miRNAs) involved in autoantibody-mediated arthritis (AMA). METHODS: A time-course microarray data (ID: GSE27492) of peripheral blood leukocytes, ankle tissue, and synovial fluid from K/BxN mouse serum-transferred mice were downloaded from Gene Expression Omnibus. Those samples were collected at days 0, 1, 3, 7, 12, and 18 after serum injection. Limma of R was employed to identify differentially expressed genes (DEGs) in samples collected at days 1-18 compared with those collected at day 0. Consistent DEGs were obtained by taking the interaction of DEGs from different time points, followed by functional enrichment analysis. MiRNAs were screened out and constructed into regulatory network with DEGs using Cytoscape. RESULTS: In total, 17 consistent DEGs were obtained, including downregulated Ephx1 and upregulated AF251705, Adam8, Arg1, Basp1, Ccl2, Ccl7, Ccl9, Ccr2, Clec4a2, Clec4d, Cxcl1, Fabp5, Fcgr1, Gp49a, Il1rn, and Saa3. Those DEGs were associated with biological processes of immune response, inflammatory response, and defense response; chemokine signaling pathway; cytokine-cytokine receptor interaction; and NOD-like receptor signaling pathway. Additionally, 202 miRNAs were identified to have a regulatory effect on 9 of the 17 DEGs. Notably, miR-944, miR-374a, and miR374b were found to regulate the expression of Cxcl1, Ccl7, and Ccl2. Clec4d was targeted by 78 miRNAs. CONCLUSIONS: Our study reveals that 17 DEGs and 202 miRNAs may be associated with autoimmune disorder in the progression of AMA, which could guide future researches.
28747601 [Leptin and autoimmune disease]. 2017 Leptin is secreted from adipocytes and acts mainly on the hypothalamus causing weight loss due to suppression of appetite and increased energy expenditure. On the other hand, the leptin receptor is also expressed in hematopoietic cells and its action on the immune system has become known, and the significance of leptin in autoimmune diseases has gradually become clear. It has been shown that leptin acts as an exacerbating factor in many autoimmune diseases and it is suggested that inhibition of leptin signal may be a novel therapeutic method for autoimmune diseases. In this article, we will outline the significance of leptin in the immune system based on the current reports.
28879718 Interleukin 6 Receptor (IL6-R) Gene Polymorphisms Underlie Susceptibility to Rheumatoid Ar 2017 Sep 1 BACKGROUND: Increased production of interleukin 6 (IL-6) is associated with rheumatoid arthritis that acts through its receptor, IL-6R (interleukin 6 receptor). Various single nucleotide polymorphisms in the IL6R gene conferring susceptibility to rheumatoid arthritis have been identified in various populations yet these associations have not been fully established. The present study was pursued with the aim to evaluate a possible association between three single nucleotide polymorphisms (rs2228145, rs4537545, rs4845617) of the IL6R gene and rheumatoid arthritis in Pakistani patients. METHODS: For this purpose, we recruited 60 patients diagnosed with rheumatoid arthritis and 60 healthy age and gender matched controls. Blood samples were collected and DNA was extracted. Sanger DNA sequencing was performed to evaluate the SNPs in IL6R and the data were statistically evaluated using chi-square test. RESULTS: Results of our study indicated that rs2228145 and rs4845617 were significantly associated with rheumatoid arthritis in Pakistani population. However, no association could be established between IL6R (rs4537545) and rheumatoid arthritis in Pakistani population. CONCLUSIONS: This study reports a possible genetic association of IL6R (rs2228145 and rs4845617) to the genetic susceptibility of rheumatoid arthritis.
28269999 Baseline MRI bone erosion predicts the subsequent radiographic progression in early rheuma 2017 Nov OBJECTIVE: To examine whether magnetic resonance imaging (MRI) findings at baseline predict radiographic progression in early-stage rheumatoid arthritis (RA) patients who have achieved sustained good clinical response. METHODS: This is a sub-analysis from the one-year observational study of Nagasaki University Early Arthritis Cohort. Definition of 'good clinical response' was a decrement of disease activity score (DAS) 28 ≧ 1.2 at three months with achievement of DAS28 remission through 6-12 months. Gd-enhanced MRI of both wrists and finger joints were examined at baseline and scored using rheumatoid arthritis magnetic resonance imaging score (RAMRIS). Annual increment of Genant-modified Sharp score (GSS) > 0 was defined as 'radiographic progression'. Predictors of radiographic progression were determined by logistic regression analysis. RESULTS: Twenty-four subjects were selected in the present study. Each median RAMRIS synovitis, bone edema, bone erosion, and GSS at baseline were 6.5, 0.5, 0, and 0, respectively. Five patients developed radiographic progression at one year. Multivariate logistic regression analysis has shown that RAMRIS bone erosion at baseline is the only independent predictor of radiographic progression at one year (p = .032). CONCLUSIONS: Our data suggest that MRI bone erosion predicts poor radiographic outcome of early-stage RA even if it has been successfully treated.
28524620 Clinical performance and survivorship of navigated floating platform mobile-bearing total 2017 Sep BACKGROUND: The purpose of this study is to report the outcome of navigation-assisted cruciate-retaining total knee arthroplasty (TKA) using one type of cemented, second-generation, floating-platform (FP), mobile-bearing system. METHODS: Forty-two patients who underwent cruciate retaining TKAs using e.motion-FP prostheses under navigational guidance were retrospectively reviewed. The preoperative diagnosis was osteoarthritis in all knees except one rheumatoid arthritis. The mean follow-up was 132.0 months (range, 120-140 months) and the mean age was 64.0 ± 4.7 years (range, 51-76 years) at the time of index surgery. Clinical and radiographic results as well as mechanical survival rate of this type of prosthesis were investigated at a minimum follow-up of 10 years. RESULTS: The mean mechanical femorotibial angle was improved from 11.7° ± 3.3° preoperatively to 1.4° ± 1.7° at the latest follow-up. No prosthesis-related complications occurred. One knee underwent open debridement due to superficial infection at 5 weeks after surgery and the other knee experienced a periprosthetic fracture around the proximal tibia, which was successfully healed after open reduction and internal fixation. CONCLUSIONS: The e.motion-floating platform mobile-bearing design yielded satisfactory long-term durability and implant performance under navigational guidance.
28363827 A multi-parameter response prediction model for rituximab in rheumatoid arthritis. 2018 Mar OBJECTIVES: To validate the IFN response gene (IRG) set for the prediction of non-response to rituximab in rheumatoid arthritis (RA) and assess the predictive performance upon combination of this gene set with clinical parameters. METHODS: In two independent cohorts of 93 (cohort I) and 133 (cohort II) rituximab-starting RA patients, baseline peripheral blood expression of eight IRGs was determined, and averaged into an IFN score. Predictive performance of IFN score and clinical parameters was assessed by logistic regression. A multivariate prediction model was developed using a forward stepwise selection procedure. Patients with a decrease in disease activity score (ΔDAS28)≥1.8 after 6 months of therapy were considered responders. RESULTS: The mean IFN score was higher in non-responders compared to responders in both cohorts, but this difference was most pronounced in patients who did not use prednisone, as described before. Univariate analysis in cohort I showed that baseline DAS28, IFN score, DMARD use and negativity for IgM-RF and/or ACPA were associated with rituximab non-response. The multivariate model consisted of DAS28, IFN score and DMARD use, which showed an area under the curve (AUC) of 0.82. In cohort II, this model revealed a comparable AUC in PREDN-negative patients (0.78), but AUC in PREDN-positive patients was significantly lower (0.63), which seemed due to effect modification of the IFN score by prednisone. CONCLUSIONS: Combination of predictive parameters provided a promising model for the prediction of non-response to rituximab, with possibilities for optimization via definition of the exact interfering effect of prednisone on IFN score. TRIAL REGISTRATION (COHORT II, SMART TRIAL): NCT01126541, registered 18 May 2010.
28291534 PTPN22 -1123G>C polymorphism and anti-cyclic citrullinated protein antibodies in rheumatoi 2017 Aug 10 BACKGROUND AND OBJECTIVES: The protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene encodes an important negative regulator of T-cell activation, lymphoid-specific phosphatase -Lyp- and has been associated with different autoimmune disorders. The PTPN22 -1123G>C polymorphism appears to affect the transcriptional control of this gene, but to date, the biological significance of this polymorphisms on rheumatoid arthritis (RA) risk remains unknown. We evaluate the association of PTPN22 -1123G>C polymorphism with anti-cyclic citrullinated protein antibodies (anti-CCP) and risk for RA in population from Western Mexico. MATERIAL AND METHODS: A transversal analytic study, which enrolled 300 RA patients classified according to ACR-EULAR criteria and 300 control subjects (CS) was conducted. The -1123 G>C polymorphism was genotyped by PCR-RFLP. The anti-CCP antibodies levels were quantified by ELISA kit. RESULTS: We found a higher prevalence of homozygous PTPN22 -1123CC genotype in CS than in RA patients (OR 0.41; 95% confidence interval 0.24-0.71; P=.001), suggesting a potential protective effect against RA. Concerning anti-CCP levels, the CC genotype carriers showed the lowest median levels in RA (P<.05). CONCLUSION: The PTPN22 -1123CC genotype is a protector factor to RA in a Mexican-mestizo population and is associated with low anti-CCP antibodies.
28143790 Association of IL17A and IL17F genes with rheumatoid arthritis disease and the impact of g 2017 Mar BACKGROUND: Previous studies have reported an association between polymorphisms in Il17A and IL17F genes and the prevalence of rheumatoid arthritis (RA) in Caucasian populations. The aim of the current study was to investigate that polymorphisms in both genes may affect RA susceptibility in the Tunisian population and to study the relation between serum IL-17 levels and synovial fluid (SF) levels and risk in RA patients. We suggested also that these polymorphisms may influence response to treatment in Tunisian RA patients. METHODS: We studied IL17A-152 G/A (rs2275913), IL17F 7488 A/G (rs763780) and IL17F 7383 A/G polymorphisms in a Tunisian population. The genotypic and allelic distributions of IL-17A and IL-17F genes polymorphisms were analyzed by Polymerase Chain-Reaction (PCR) and Restriction Fragment Length Polymorphism (RFLP) for 108 patients and 202 healthy controls. IL-17 levels were measured in synovial fluid (SF) and in serum of both 108 patients and 47 controls (pg/ml) using enzyme-linked immunosorbent assay (ELISA) technique. RESULTS: Our results indicated that IL17F 7488 A/G and IL17F 7383 A/G polymorphisms were significantly associated with RA risk in the whole population. However, IL17A-152 G/A polymorphism did not show any significant association with RA prevalence in the Tunisian population. Stratification according to demographic and clinical features revealed differential significant associations of IL17A-152 G/A, IL17F 7488 A/G and IL17F 7383 A/G polymorphisms within different subgroups and subtypes of clinical-pathologic features in RA patients. IL17A-152 G/A polymorphism was associated with an enhanced response to biologic and MTX treatment. IL17F 7383 A/G polymorphism was associated with an enhanced response to biologic treatment. The IL17F 7488 A/G polymorphism decreased significantly good response to biologic treatment, but enhanced response to MTX treatment. The expression of IL-17 in serum and synovial fluid (SF) in RA patients was significantly higher than that observed in healthy controls (P<0.0001) and their levels depend on RA severity. The mean IL-17 levels in the anti-TNF α treated patients decreased significantly at 0 week, 14 weeks and 30 weeks (P=0.0032 and P<0.0001, respectively). CONCLUSIONS: Our results confirmed IL17A and IL17F as potential candidate genes involved in RA. They play pivoting roles in the susceptibility and in clinical features of RA disease. Responses to RA treatments are differently conditioned by polymorphisms in IL17A and IL17F genes.
28282363 The Relationship Between Mental Health, Disease Severity, and Genetic Risk for Depression 2017 Jul/Aug OBJECTIVE: Reduced mental health (MH) is prevalent in rheumatoid arthritis (RA). Although longitudinal studies are limited, there is evidence that depression is associated with worse disease outcomes. We evaluated reciprocal relationships between MH, RA severity, and genetic risks for depression for 2 years in a well-characterized cohort of RA patients. METHODS: We evaluated 520 early RA patients previously enrolled to two clinical trials. MH was measured using the short form-36 MH domain and mental component summary scores (MCS). MCS/MH associations over 2 years with disease activity (disease activity score on a 28-joint count), disability (health assessment questionnaire), pain visual analog scale scores, and a weighted genetic risk score for depression were tested using linear mixed-effects and regression models. RESULTS: Poorer MH was associated with worse RA outcomes. Lower MCS scores (indicating worse MH) were seen in patients with a greater genetic risk for depression (weighted genetic risk score: coefficient = -1.21, p = .013). Lower baseline MCS was associated with lower 2-year improvements in disease activity score on a 28-joint count (coefficient = -0.02, p < .001), pain (coefficient = -0.33, p < .001), and health assessment questionnaire (coefficient = -0.01, p = .006). Baseline MCS was associated with changes in the swollen joint count (coefficient = -0.09, p < .001) and patient global assessment (coefficient = -0.28, p < .001) but not the tender joint count (p = .983) and erythrocyte sedimentation rate (p = .973). Only baseline pain visual analog scale (coefficient = -0.07, p = .002) was associated with 2-year changes in MCS. CONCLUSIONS: Reduced baseline MH was associated with lower improvements in disease activity, disability, and pain for 2 years, supporting current national guidelines recommending screening for depression in RA. Pain had a bidirectional relationship with MH. Depression genetic risk had a significant association with MH.
28792533 Increased amount of phosphorylated proinflammatory osteopontin in rheumatoid arthritis syn 2017 BACKGROUND: Osteopontin (OPN) is an immunoregulatory protein which production increases in both rheumatoid arthritis (RA) and osteoarthritis (OA). Phosphorylated osteopontin (Phospho-OPN) is known to increase macrophage and osteoclast activation, this process is controlled by extracellular tartrate-resistant acid phosphatase (TRAcP), also a biomarker for RA. Here, we evaluated the phosphorylation status of OPN in RA and OA synovia, as well as its correlation with TRAcP isoforms. METHODS: Synovial tissue and fluid were obtained from 24 RA (14 seropositive and 10 seronegative) and 24 OA patients. Western blotting was used to analyze the extent of OPN phosphorylation. TRAcP isoforms were measured in synovial fluid using ELISA; immunohistochemistry assessed the distribution of OPN and TRAcP expressing cells in the synovial tissue, especially distinguishing between the TRAcP isoforms. RESULTS: Full-length OPN was more phosphorylated in RA than in OA (p<0.05). The thrombin cleaved C-terminal end of OPN was also more phosphorylated in RA (p<0.05). RA patients had a lower concentration of TRAcP 5B and higher concentration of less active 5A in their synovial fluid compared to OA patients. The TRAcP 5B/5A ratio was decreased in RA and correlated negatively with the amount of phospho-OPN (p<0.05). TRAcP positive cells for both isoforms were found all along the synovial lining; OPN antibody staining was localized in the extracellular matrix. CONCLUSION: Our data suggests that in RA the synovial fluid contains insufficient amounts of TRAcP 5B which increase levels of the proinflammatory phospho-OPN. This may lead to increased macrophage and osteoclast activation, resulting in the increased local inflammation and bone resorption present in RA joints.