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ID PMID Title PublicationDate abstract
31818504 [Not Available]. 2020 May INTRODUCTION: Anakinra is an anti-IL-1RA targeting IL-1β with a central role in the occurrence of auto-inflammatory diseases. Its use is not without risk. CASE REPORT: We report a case of late onset auto-inflammatory syndrome treated with anti-IL-1RA whose progression was marked by deep isolated thrombocytopenia, rapidly regressive after discontinuation of anakinra. CONCLUSION: Immuno-allergic thrombocytopenia to anakinra is a rare, but serious adverse event.
32977033 Does Rheumatoid Arthritis Affect the Infection and Complications Rates of Spinal Surgery? 2021 Jan BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disease that produces synovial membrane inflammation and causes progressive articular damage with function loss. Some controversy exists regarding whether RA is associated with infection and complications after spinal surgery. The present study aimed to determine the effect of RA on spinal surgery infection and complications. METHODS: A systematic literature search was performed in accordance with the PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines. All studies that had compared patients who had undergone spinal surgery with and without RA were included in the analysis. RESULTS: We found significantly greater rates statistically of complications (odds ratio [OR], 1.43; 95% confidence interval [CI], 1.20-1.70; P < 0.05) and infections (OR, 1.69; 95% CI, 1.46-1.95, P < 0.05) in those with RA than in those without RA after spinal surgery. When registry data were excluded, the results suggested that the incidence of complications (OR, 2.24; 95% CI, 0.92-5.44; P = 0.08) and infections (OR, 1.76; 95% CI, 1.50-2.07; P < 0.05) was still greater for the RA group than for the non-RA group. CONCLUSION: When undergoing spinal surgery, patients with RA have a greater risk of operative complications and infection. Surgeons should be aware of these risks and appropriately plan spinal operation for patients with RA to reduce the risk of complications.
31982560 Engineered DNA nanodrugs alleviate inflammation in inflammatory arthritis. 2020 Mar 15 Rheumatoid arthritis (RA) is an autoimmune disease featured with chronic joint inflammation. Suppression of inflammation is critical to RA treatment and joint protection. In this study, DNA nanodrugs are prepared via the conjugation of NF-κB decoy oligodeoxynucleotides (dODNs) and VCAM-1 targeted peptides (P) onto self-assembled DNA tetrahedrons (TDs). Physicochemical properties of DNA nanodrugs are characterized using atomic force microscopy (AFM), gel electrophoresis and Fourier Transform Infrared Spectrometer (FTIR). Cytotoxicity, cellular uptake and anti-inflammatory efficacy of DNA nanodrugs are evaluated in vitro. Clinical arthritis index, inflammatory proteins in serum and joint pathophysiology are also investigated in vivo. TD-P-dODN possesses one dODN and one P and exhibits faster and higher cellular uptake by inflammatory cells compared with free dODNs. TD-P-dODN also significantly reduce inflammatory proteins in cells and adjuvant induced arthritis (AIA) mice. Reduced clinical arthritis index and improved joint rehabilitation are also achieved by TD-P-dODN treatment. This study demonstrates that an engineered DNA nanodrug (TD-P-dODN) enhances the efficacy of nucleic acid drugs and represents a promising strategy for RA treatment.
32989619 Validation of Fully Automatic Quantitative Software for Finger Joint Space Narrowing Progr 2020 Dec In rheumatoid arthritis (RA), the radiographic progression of joint space narrowing (JSN) is evaluated using visual assessments. However, those methods are complicated and time-consuming. We developed an automatic system that can detect joint locations and compute the joint space difference index (JSDI), which was defined as the chronological change in JSN between two radiographs. The purpose of this study was to establish the validity of the software that automatically evaluates the temporal change of JSN. This study consisted of 39 patients with RA. All patients were treated with tocilizumab and underwent hand radiography (left and right hand separately) at 0, 6, and 12 months. The JSN was evaluated using mTSS (modified Total Sharp Score) by one musculoskeletal radiologist as well as our automatic system. Software measurement showed that JSDI between 0 and 12 months was significantly higher than that between 0 and 6 months (p < 0.01). While, there was no significant difference in mTSS between 0, 6, and 12 months. The group with higher disease activity at 0 months had significantly higher JSDI between 0 and 6 months than that with lower disease activity (p = 0.02). The automatic software can evaluate JSN progression of RA patients in the finger joint on X-ray.
33012711 Simultaneous bilateral aqueous misdirection following certolizumab therapy for rheumatoid 2020 Oct 4 Aqueous misdirection syndrome is a rare, incompletely understood, sight-threatening eye condition that is difficult to diagnose and treat. We present a case of simultaneous bilateral aqueous misdirection following the administration of certolizumab in a 41-year-old women with rheumatoid arthritis and no known risk factors. To our knowledge, aqueous misdirection has not previously been associated with the use of tumour necrosis factor-alpha inhibitors.
32798838 Productivity Loss in Patients With Chronic Diseases: A Pooled Economic Analysis of Hungari 2020 Sep OBJECTIVES: To assess productivity loss (PL) variations across a set of chronic diseases and analyze significant PL drivers (demographics, health status, healthcare resource use) in Hungary. METHODS: Data from 11 cost-of-illness studies (psoriasis, dementia, systemic sclerosis, multiple sclerosis, benign prostatic hyperplasia, Parkinson's disease, psoriatic arthritis, rheumatoid arthritis, schizophrenia, epilepsy, and diabetes) were pooled, and patient-level data were analyzed. A weighted multiple linear regression analysis was run to identify significant PL indicators. All costs were adjusted to 2018 euro rates and PL was further presented as a proportion of gross domestic product/capita, facilitating results comparability and transferability. RESULTS: The dataset comprised 1888 patients from 11 chronic diseases. The average indirect cost/(gross domestic product/capita) ratio was highest in schizophrenia (72.4%) and rheumatoid arthritis (71.3%) and lowest in benign prostatic hyperplasia (1.6%). Correlation results infer that a higher EuroQol 5-dimension 3-level index score was significantly associated with lower PL. The number of hospital admissions was the main contributor toward increasing PL among resource use indicators. Age and sex showed inconsistent and insignificant correlations with PL. In regression analysis, a better EuroQol 5-dimension 3-level index score and higher education were consistently associated with decreasing PL in all models. CONCLUSIONS: This article will enable health decision makers to understand the importance of adopting a societal perspective for chronic disease reimbursement decisions. The correlation between PL and health status supports that timely started effective treatments may prevent patients from losing their workability.
32613582 The Use of Augmented Reality to Raise Awareness of the Differences Between Osteoarthritis 2020 Arthritis is one of the most common disease states worldwide but is still publicly misunderstood and lacks engaging public awareness materials. Within the UK, the most prevalent types of arthritis are osteoarthritis (OA) and rheumatoid arthritis (RA). The two are commonly mistaken as the same disease but, in fact, have very different pathogenesis, symptoms and treatments. This chapter describes a study which aimed to assess whether an augmented reality (AR) application could be used to raise awareness about the difference between OA and RA.An application was created for Android tablets that included labelled 3D models, animations and AR scenes triggered from a poster. In total 11 adult participants tested the application taking part in a pretest and posttest which aim to measure the usability of the application and the acquisition of knowledge on OA and RA. A T-test was performed to assess the effectiveness of the application from the pretest and posttest questionnaire outcomes. Overall results were encouraging reporting a very significant acquisition of knowledge and a highly satisfactory user experience.
32241617 Clinical characteristics associated with drug-free sustained remission in patients with rh 2020 Dec OBJECTIVES: There is limited information on treatment withdrawal in patients with rheumatoid arthritis (RA). This study investigated the clinical course after stopping disease-modifying anti-rheumatic drugs (DMARDs) in patients with well-controlled RA and the clinical features associated with disease flare. METHODS: Among patients in the Korean Intensive Management of Early Rheumatoid Arthritis (KIMERA) cohort, discontinuation of DMARDs was determined by a shared decision between patient and rheumatologist. Drug-free remission was defined as (1) non-use of DMARDs and corticosteroids, (2) Disease Activity Score in 28 joints (DAS28) <2.6, and (3) no evidence of synovitis. The maintenance rate of drug-free remission and the predictors for flare were evaluated using Cox proportional hazard models. RESULTS: Of 234 patients, 50 patients discontinued DMARDs. All but one using etanercept were treated with conventional synthetic DMARDs. The median follow-up duration was 30 months, and 31 patients (62%) experienced disease flare after stopping DMARDs. The maintenance rate of drug-free remission was 94.0%, 86.7%, and 46.1% at 12, 24, and 48 months, respectively. Disease flare was correlated with longer time to remission, failure of initial DMARDs, and longer duration of disease and higher disease activity at DMARD withdrawal (P = 0.001, 0.022, 0.010 and 0.037, respectively). In multivariate analyses, longer duration of disease (>24 months) and higher disease activity (DAS28 >2.26) at DMARD withdrawal was independently associated with disease flare. CONCLUSION: Drug-free remission was feasible in selected patients with well-controlled RA. Patients with early RA and lower disease activity at DMARD withdrawal are more likely to maintain the drug-free remission.
33201634 [Risk factors for disseminated herpes zoster]. 2020 Sep 16 BACKGROUND: When skin abnormalities in patients extend over several dermatomes, disseminated herpes zoster should be suspected. This complication is most often seen in immunocompromised patients. CASE DESCRIPTION: An 87-year-old patient came to the dermatology outpatient clinic with several vesicles scattered over her body. She was being treated with methotrexate for rheumatoid arthritis. Upon physical examination, we found groups of vesicles in the area of the maxillary nerve as well as several solitary vesicles scattered over her body. We made the diagnosis of 'disseminated herpes zoster'. PCR test of fluid from one of the vesicles found Varicella zoster virus. We treated the patient with intravenous acyclovir for 48 hours after which we treated her with oral acyclovir for another 8 days. We temporarily halted methotrexate. Outpatient follow-up found that the patient's skin abnormalities had diminished significantly. CONCLUSION: The risk of disseminated herpes zoster depends on several factors. Use of immunosuppressants is often not the only contributing factor. Risk of disseminated herpes zoster in a patient who is being treated with methotrexate depends on age, comorbidities and co-medication of the patient.
33117342 Leonurine Regulates Treg/Th17 Balance to Attenuate Rheumatoid Arthritis Through Inhibition 2020 Leonurine, an active alkaloid extracted from Herba leonuri, is reported to have potent anti-inflammatory activity against rheumatoid arthritis (RA). However, the molecular mechanism of action of leonurine in RA remains poorly understood. In this study, we detected 3,425 mRNAs differentially expressed between CD4(+) T cells of RA patients and those of healthy individuals using microarray raw data mining. Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that transcriptional coactivator with PDZ-binding motif (TAZ) regulates a variety of biological processes including T-helper (Th)-17 cell development, and was thus selected for functional verification. In a naïve CD4(+) T cell differentiation assay, we found that TAZ overexpression was associated with impaired balance between T regulatory (Treg) and Th17 cells in vitro. TAZ overexpression increased the levels of the pro-inflammatory cytokines interleukin (IL)-17, IL-1β, and tumor necrosis factor (TNF)-α and decreased that of the anti-inflammatory cytokine IL-10. Leonurine treatment had a direct recovery effect on the impaired balance and reduced the expression of TAZ and led to normalization of IL-17, IL-1β, and TNF-α and IL-10. Furthermore, IL-6 was found to promote the expression of TAZ and receptor activator of nuclear factor kappa-B ligand (RANKL), and RANK. Leonurine significantly inhibited TAZ-mediated expression of RANKL, and RANK and IL-6 in synovial fibroblasts. We conclude that the therapeutic effect of leonurine was through suppression of TAZ led to restoration of Treg/Th17 balance and suppression of synovial fibroblast action.
32052376 Systematic Literature Review of Economic Evaluations of Biological Treatment Sequences for 2020 May OBJECTIVE: This systematic literature review (SLR) had two objectives: to analyse published economic evaluations of biological disease-modifying anti-rheumatic drugs (bDMARDs) for patients with moderate to severe rheumatoid arthritis (RA) previously treated with DMARDs and to assess the quality of those that included sequences of treatments. METHODS: We performed an SLR on PubMed, Central, Cochrane, and French databases from January 2000 to December 2018. The search focused on cost-effectiveness/utility/benefit analyses. We extracted data on treatment sequences, outcomes (e.g. quality-adjusted life year) and choices of economic evaluation methods (e.g. model type, type of analysis, and method of utility estimation). We analysed the improvement of methods by comparing two sub-periods (2000-2009 and 2010-2018). The quality of reporting and the quality of the methods were assessed using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) and a set of eight key aspects for a reference case for economic evaluation of bDMARDs based on the Outcome Measures in Rheumatology (OMERACT) and Drummond checklists. Data extraction and study assessment were performed independently by two health economists. RESULTS: From the 824 records identified in the initial search, 51 publications were selected. Of these, 31 included sequences. Individual models such as discrete-event simulations were used in over two-fifths (22/51, 43%) of the selected studies. Few studies (7/51, 14%) used utility scores based on generic instruments (e.g. EQ-5D). Estimation of hospitalization costs was described in only approximately one-third of studies (19/51). Loss of quality of life (QoL) related to adverse events such as tuberculosis and pneumonia was included in one-tenth (5/51, 10%) of the studies. It was difficult to compare the results of the economic evaluations (i.e. incremental cost-effectiveness ratios) due to the high heterogeneity of studies in terms of disease stage, data sources, inputs, and methods of health outcome assessment used. For identified studies including sequences, the CHEERS assessment of reporting quality showed insufficient reporting of uncertainty analyses and utility weights in more than a third of the studies (11/31, 35%; 9/25, 36%). An in-depth assessment of the quality of the studies revealed that only seven, mostly conducted during the sub-period 2010-2018, addressed the majority of methodological quality assessment issues such as the simulation of patient sequence pathways, the use of systematic reviews and meta-analyses of comparative effectiveness, the choice of treatment sequence, and rules for switching. CONCLUSION: Our SLR identified a lack of high-quality evaluations assessing bDMARD sequences, although some improvements were made in the reporting and modelling of patients' pathways in studies published after 2010. In order to improve economic evaluations of RA, clear health technology assessment guidance on RA health-related QoL instruments must be provided, and data including long-term disease progression must be made available.
33287268 Factors Associated with Objectively Measured Physical Activity in Patients with Seropositi 2020 Dec 3 Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease, which is associated with low levels of physical activity (PA). However, the factors related to low physical activity levels have rarely been studied. Methods: In this cross-sectional study, 70 seropositive RA patients were included. Physical activity was objectively assessed with an ActiGraph GT3X+ accelerometer. In addition, body mass index, smoking status, work ability, and clinical parameters (functional disabilities, disease activity, disease duration, pain, and inflammation parameters) were measured. Results: RA patients performed a mean of 215.2 (SD: 136.6) min a week of moderate physical activity and 9.1 (SD: 26.3) min of vigorous physical activity. The total amount of moderate and vigorous physical activity (MVPA) was associated with BMI, and functional disabilities. In addition, non-smokers and patients with better work ability did more MVPA. No association could be seen with disease activity, disease duration, pain, and inflammatory markers. After mutual adjusting of all the variables, only BMI showed a significant relationship with MVPA. Conclusions: RA patients perform de facto no physical activity with vigorous intensity. Factors related to low physical activity are BMI, functional disabilities, workability and smoking status, whereas due to the study design no causal and temporal link could be made.
31286174 Vitamin D, Autoimmune Disease and Rheumatoid Arthritis. 2020 Jan Vitamin D has been reported to influence physiological systems that extend far beyond its established functions in calcium and bone homeostasis. Prominent amongst these are the potent immunomodulatory effects of the active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25-(OH)(2)D3). The nuclear vitamin D receptor (VDR) for 1,25-(OH)(2)D3 is expressed by many cells within the immune system and resulting effects include modulation of T cell phenotype to suppress pro-inflammatory Th1 and Th17 CD4+ T cells and promote tolerogenic regulatory T cells. In addition, antigen-presenting cells have been shown to express the enzyme 1α-hydroxylase that converts precursor 25-hydroxyvitamin D3 (25-OHD3) to 1,25-(OH)(2)D3, so that immune microenvironments are able to both activate and respond to vitamin D. As a consequence of this local, intracrine, system, immune responses may vary according to the availability of 25-OHD3, and vitamin D deficiency has been linked to various autoimmune disorders including rheumatoid arthritis (RA). The aim of this review is to explore the immune activities of vitamin D that impact autoimmune disease, with specific reference to RA. As well as outlining the mechanisms linking vitamin D with autoimmune disease, the review will also describe the different studies that have linked vitamin D status to RA, and the current supplementation studies that have explored the potential benefits of vitamin D for prevention or treatment of RA. The overall aim of the review is to provide a fresh perspective on the potential role of vitamin D in RA pathogenesis and treatment.
31935514 A significant decrease of BAFF, APRIL, and BAFF receptors following mesenchymal stem cell 2020 Mar 30 In the present study, we aimed to evaluate effects of autologous mesenchymal stem cells (MSCs) intravenous administration on the response of B cells, BAFF, APRIL, and their receptors on the surface of B cells at 1, 6, and 12 month follow-up periods in refractory rheumatoid arthritis (RA) patients. Thirteen patients with refractory RA received autologous MSCs. Plasma levels of BAFF and APRIL were measured employing ELISA method, followed by estimating B cell population and BAFFRs evaluation by flow cytometry technique. Gene expression of BAFF, APRIL, and their receptors on B cell surface in PBMCs was evaluated by SYBR Green real-time PCR technique. Plasma concentration of BAFF significantly decreased 1 and 6 months after the MSCT (MSCs Transplantation). Plasma concentration of APRIL significantly decreased 1 month after the MSCT. Percentages of CD19 + B cells in the PBMC population significantly decreased 12 months after the MSCT. Percentages of BR3 + CD19 + B cells and BCMA + CD19 + B cells significantly decreased at the 12th month after the MSCT. The gene expression of BAFF in the PBMC population significantly decreased during 6, and 12 months after the MSCT. The gene expression of APRIL significantly decreased on month 6 after the MSCT. The gene expression of BR3 significantly decreased during 1, 6, and 12 months after the MSCT. The MSCT seems to decrease B cells response because of the reduced production of BAFF and APRIL cytokines and decrease the expression of their receptors on the surface of B cells.
32607803 Perfusion in hand arthritis on dynamic contrast-enhanced computed tomography: a randomized 2021 Jan OBJECTIVE: To evaluate the performance of dynamic contrast-enhanced CT (DCE-CT) in detecting and quantitatively assessing perfusion parameters in patients with arthritis of the hand compared with dynamic contrast-enhanced MRI (DCE-MRI) as a standard of reference. MATERIALS AND METHODS: In this IRB-approved randomized prospective single-centre study, 36 consecutive patients with suspected rheumatoid arthritis underwent DCE-CT (320-row, tube voltage 80 kVp, tube current 8.25 mAs) and DCE-MRI (1.5 T) of the hand. Perfusion maps were calculated separately for mean transit time (MTT), time to peak (TTP), relative blood volume (rBV), and relative blood flow (rBF) using four different decomposition techniques. Region of interest (ROI) analysis was performed in metacarpophalangeal joints II-V and in the wrist. Pairs of perfusion parameters in DCE-CT and DCE-MRI were compared using a two-tailed t test for paired samples and interpreted for effect size (Cohen's d). According to the Rheumatoid Arthritis Magnetic Resonance Imaging Score (RAMRIS) scoring results, differentiation of synovitis-positive and synovitis-negative joints with both modalities was assessed with the independent t test. RESULTS: The two modalities yielded similar perfusion parameters. Identified differences had small effects (d 0.01-0.4). DCE-CT additionally differentiates inflamed and noninflamed joints based on rBF and rBV but tends to underestimate these parameters in severe inflammation. The total dose-length product (DLP) was 48 mGy*cm with an estimated effective dose of 0.038 mSv. CONCLUSION: DCE-CT is a promising imaging technique in arthritis. In patients with a contraindication to MRI or when MRI is not available, DCE-CT is a suitable alternative to detect and assess arthritis.
31544696 Is Rheumatoid Arthritis a Risk Factor for Fractures: A Systematic Review of Observational 2020 AIM: The primary objective was to assess the risk of fractures in adults with RA compared with controls from the general population. The review also assessed an increased risk of fractures in RA patients when accounting for steroid use, RA disease severity or functional impairment. METHODS: Citations were screened from MEDLINE, EMBASE, Cochrane Database of Systematic Reviews and CINAHL. Included citations were written in English, including adult patients at least 18 years of age and compared fracture incidence or prevalence between RA patients and a control group. Case-control, cohort and cross-sectional studies were included. RESULTS: There were a total of 3451 citations; after application of the inclusion criteria, 17 studies were selected. In 14 of the 17 studies, there was an increase in the risk of fracture in RA patients compared to controls. In studies that evaluated for glucocorticoid use, four of 13 demonstrated an increased risk of fracture with glucocorticoid use, however, only two of these four studies specifically assessed glucocorticoid use amongst patients with RA. In studies that analyzed RA severity or functional impairment, two of seven demonstrated disease severity or impairment as a risk factor for fracture. There was marked study heterogeneity in terms of patient and fracture characteristics, which was a limitation of the analysis that impeded the ability to make direct comparisons. CONCLUSION: The risk of fracture in RA patients is elevated when compared to the general population, although the etiology of the increased risk remains to be elucidated.
32555708 Patient-physician discrepancy in the perception of immune-mediated inflammatory diseases: 2020 INTRODUCTION: Recommendations on chronic diseases management emphasise the need to consider patient perspectives and shared decision-making. Discrepancies between patients and physicians' perspectives on treatment objectives, disease activity, preferences and treatment have been described for immune-mediate inflammatory diseases. These differences could result on patient dissatisfaction and negatively affect outcomes. OBJECTIVE: To describe the degree of patient-physician discrepancy in three chronic immune-mediated inflammatory diseases (rheumatoid arthritis [RA], psoriatic arthritis [PsA] and psoriasis [Ps]), identifying the main areas of discrepancy and possible predictor factors. METHODS: Qualitative systematic review of the available literature on patient and physician discrepancies in the management of RA, PsA and Ps. The search was performed in international (Medline/PubMed, Cochrane Library, ISI-WOK) and Spanish electronic databases (MEDES, IBECS), including papers published from April 1, 2008 to April 1, 2018, in English or Spanish, and conducted in European or North American populations. Study quality was assessed by the Oxford Centre for Evidence-Based Medicine criteria. RESULTS: A total of 21 studies were included (13 RA; 3 PsA; 4 Ps; 1 RA, Ps, and Axial Spondyloarthritis). A significant and heterogeneous degree of discrepancy between patients and physicians was found, regarding disease activity, treatment, clinical expectations, remission concept, and patient-physician relationship. In RA and PsA, studies were mainly focused on the evaluation of disease activity, which is perceived as higher from the patient's than the physician's perspective, with the discrepancy determined by factors such as patient's perception of pain and fatigue. In Ps, studies were focused on treatment satisfaction and patient-physician relationship, showing a lower degree of discrepancy in the satisfaction regarding these aspects. CONCLUSIONS: There is a significant degree of patient-physician discrepancy regarding the management of RA, PA, and Ps, what can have a major impact on shared decision-making. Future research may help to show whether interventions considering discrepancy improve shared decision-making.
31549885 Association of HLA-G 3'UTR Polymorphisms with Soluble HLA-G Levels and Disease Activity in 2020 Feb Background: Human leukocyte antigen (HLA)-G antigens are inducible non-classical major histocompatibility complex class Ib molecules which play an important role in the regulation of inflammatory processes and immunomodulation in autoimmune diseases. There are controversial reports on the impact of HLA-G gene polymorphisms on rheumatoid arthritis (RA). This study aimed at examining the impact of 14 base pair (bp) ins/del (rs66554220) and +3142G>C (rs1063320) polymorphisms and correlating these with soluble HLA-G (sHLA-G) levels to understand the susceptibility to RA in our sample cohort.Methods: Genomic DNA from 140 RA patients and 125 healthy controls was isolated using the salting out method. The genotyping of two polymorphisms of HLA-G (+3142G>C and 14 bp ins/del) was done by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) and PCR method, respectively. Levels of sHLA-G were estimated by ELISA and disease activity was calculated by disease activity score (DAS28-ESR).Results: The HLA-G +3142G>C polymorphism was found to be associated with a decreased risk of RA as attributed to recessive inheritance tested model results (OR = 0.4, 95%C.I. = 0.2-0.9, p = .0313*, GG + GC versus CC). Our finding did not support an association between HLA-G 14 bp ins/del variant and risk/protection of RA. The sHLA-G levels were significantly lower in +3142GG and +3142GC RA patients as compared to healthy controls.Conclusion: HLA-G +3142G>C gene polymorphism might decrease the risk of occurrence of RA in our sample cohort as +3142CC genotype is associated with increased sHLA-G levels.Abbreviations: HLA-G: human leukocyte antigen-G; RA: rheumatoid arthritis; MHC: major histocompatibility complex; UTR: untranslated region; URR: upstream regulatory region; SLE: systemic lupus erythematous; PCR-RFLP: polymerase chain reaction restriction fragment length polymorphism; sHLA-G: soluble HLA-G; bp: base pair; ACR/EULAR: American College of Rheumatology/European League against Rheumatism; RF: rheumatoid factor; Anti-CCP: anti-cyclic citrullinated peptide; DAS28-ESR: Disease Activity Score 28- Erythrocyte Sedimentation Rate; TJC: tender joint count; SJC: swollen joint count; ESR: erythrocyte sedimentation rate; PGA: patient global assessment; HTN: hypertension; DM: diabetes mellitus; TB: tuberculosis; IEC: Institute Ethics Committee; ELISA: enzyme linked immunosorbent assay; ROC: receiver operating characteristics; AUC: area under curve; SNP: single nucleotide polymorphism; MTX: methotrexate; DMARDs: disease modifying anti-rheumatic drugs; Treg: regulatory T cells; IL: interleukinUnits: soluble HLA-G: Units/mL {U/mL}.
32042094 A high-resolution HLA imputation system for the Taiwanese population: a study of the Taiwa 2020 Oct An imputation algorithm for human leukocyte antigen (HLA) is helpful for exploring novel disease associations. However, population-specific HLA imputation references are essential for achieving high imputation accuracy. In this study, a subset of 1012 individuals from the Taiwan Biobank (TWB) who underwent both whole-genome SNP array and NGS-based HLA typing were used to establish Taiwanese HLA imputation references. The HIBAG package was used to generate the imputation references for eight HLA loci at a two- and three-field resolution. Internal validation was carried out to evaluate the call threshold and accuracy for each HLA gene. HLA class II genes found to be associated with rheumatoid arthritis (RA) were validated in this study by the imputed HLA alleles. Our Taiwanese population-specific references achieved average HLA imputation accuracies of 98.11% for two-field and 98.08% for three-field resolution. The frequency distribution of imputed HLA alleles among 23,972 TWB subjects were comparable with PCR-based HLA alleles in general Taiwanese reported in the allele frequency net database. We replicated four common HLA alleles (HLA-DRB1*03:01, DRB1*04:05, DQA1*03:03, and DQB1*04:01) significantly associated with RA. The population-specific references provide an informative tool to investigate the associations of HLA variants and human diseases in large-scale population-based studies.
32361822 Understanding Refractory Rheumatoid Arthritis: Implications for a Therapeutic Approach. 2020 Jun Refractory rheumatoid arthritis (RA) has emerged as an area of unmet need in a landscape of generally well-controlled disease. Whilst most patients are adequately treated on methotrexate and other first-line disease-modifying anti-rheumatic drugs (DMARDs), a proportion requires biologic (b) and targeted synthetic (ts) DMARDs, with a further subsection failing multiple agents. Recent observational studies have adopted working definitions of refractory RA based on number of failed DMARDs, with prevalence estimates of 6-21% depending on threshold and study population. Risk factors include treatment delay, baseline disease activity and function, female gender, smoking, obesity and lower socioeconomic status. Practical and conceptual challenges in defining refractory RA arise from limitations of disease activity scores used to assess response, with attendant misclassification risk of co-existent non-inflammatory pathology, and failure to capture additional outcomes, such as fatigue, that have variable treatment response. Time is an important factor in defining refractory disease; registry studies show that growing treatment options have resulted in rapid b/tsDMARD cycling and earlier refractory status, and refractory RA is itself a dynamic concept, evolving with each new therapeutic class. Whilst the biology underpinning refractory RA remains largely unknown, a general overview of biomarker studies and clinical trials old and new offers insights into prediction of response and treatment failure. Whilst the future holds promise, current data are insufficient to personalise or meaningfully sequence b/tsDMARDs. Therefore, avoidance of a refractory course is best achieved by following proven management paradigms (e.g. early diagnosis and treat-to-target), addressing modifiable risk factors, and considering enrolment in novel trials.