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ID PMID Title PublicationDate abstract
34569172 Are We on the Same Page?: A Cross-Sectional Study of Patient-Clinician Goal Concordance in 2021 Sep 27 OBJECTIVE: Patient-clinician goal concordance is associated with improved outcomes in certain chronic diseases, but not explored in rheumatoid arthritis (RA). We examined goal concordance, correlates of concordance, and the association of concordance with health outcomes. METHODS: Adult RA patients seen ≥1 time in prior 12 months at one of two rheumatology clinics participated. Patients and their clinician independently ranked top three goals for RA treatment from eight options prior to a routine visit. Patients completed post-visit surveys on health, demographics, health literacy, and adherence. Goal concordance was defined as the patient's #1 goal being among the clinician's top three goals for that patient. Bivariable and multivariable logistic regression models were used to examine correlates of concordance. RESULTS: Patients were 58% female, 16% Spanish-speaking, and 29% had limited health literacy. Among 204 patient-clinician dyads, 20% were goal-discordant. "Have less pain" was selected by both patient and clinician in 81% of dyads, followed by "have fewer problems doing daily activities" by 63%. Otherwise, clinicians prioritized avoiding side effects, while patients ranked improved sleep, fatigue, and mood. Longer disease duration was associated with discordance (median 13.3 years, IQR 5.2-20 among discordant vs. 7 years, IQR 4-14; p=0.039); higher depressive symptoms were associated with concordance (8.1% vs 24%, p=0.04). Goal concordance was associated with higher medication adherence (AOR 2.76, 95% CI 1.01-7.56). CONCLUSION: One in five patient-clinician dyads had discordant treatment goals. Goal concordance was associated with higher medication adherence. Studies to improve goal elicitation and communication of RA patients' priorities are needed.
34232556 Interval between symptom onset and diagnosis among patients with autoimmune rheumatic dise 2021 Aug AIM: The interval between symptom onset and diagnosis (pre-diagnosis interval) can at times be longer than is ideal in patients with autoimmune rheumatic diseases (ARDs). In this study, we aimed to characterize this interval and to identify its associated factors. METHOD: We characterized pre-diagnosis interval into 4 intervals: Interval #1 between symptom onset and first visit to healthcare professionals; Interval #2 between first visit to healthcare professionals and rheumatology referral; Interval #3 between rheumatology referral and first rheumatology assessment; and Interval #4 between first rheumatology assessment and diagnosis. Median regression models were used to identify factors associated with longer pre-diagnosis interval and Interval #1. RESULTS: Among 259 patients (median age = 52.0 [41.6-61.9] years, 71% female, rheumatoid arthritis [n = 75], axial spondyloarthritis [axSpA] [n = 40] and psoriatic arthritis [n = 35]), median pre-diagnosis interval was 11.5 (4.7-36.0) months. Interval #1 (median = 4.9 months) was significantly longer than Intervals #2-#4 (median = 0.3, 1.5, and 0.0 months, respectively). Patients with axSpA had significantly longer pre-diagnosis interval (median = 38.7 months) and Interval #1 (median = 26.6 months) than patients with the other ARDs. Median regression suggested that patients referred from specialty care had significantly longer pre-diagnosis interval (median difference = 7.7 months) and Interval #1 (median difference = 6.4 months) compared to those referred from primary care. CONCLUSION: A long pre-diagnosis interval was observed among patients with ARDs (especially axSpA), due largely to a long interval between symptom onset and the first visit to healthcare professionals. This highlights the importance of interventions targeting patients prior to their first visit to healthcare professionals in reducing pre-diagnosis interval.
34623035 The Association Between Inflammation, Incident Heart Failure, and Heart Failure Subtypes i 2021 Oct 8 OBJECTIVES: In RA, there are limited data on risk factors for clinical heart failure (HF) subtypes, HF with reduced ejection fraction (HFrEF) and preserved EF (HFpEF). This study examined the association between inflammation and incident HF subtypes in RA. Since inflammation changes over time with disease activity, we hypothesized that the effect of inflammation may be stronger at five-year follow-up compared to the standard ten-year from general population studies of cardiovascular risk. METHODS: We studied an electronic health record (EHR)-based RA cohort with data pre-/post-RA incidence. We applied a validated approach to identify HF, and extract EF to classify HFrEF and HFpEF. Follow-up started from the RA incidence date (index-date) to the earliest occurrence of incident HF, death, last EHR encounter, or ten-years. Baseline inflammation was assessed using erythrocyte sedimentation rate or C-reactive protein values. Covariates included demographics, established HF risk factors, and RA-related factors. We tested the association between baseline inflammation with incident HF and its subtypes using Cox proportional hazards models. RESULTS: We studied 9087 RA patients; 8.2% developed HF during ten years of follow-up. Elevated inflammation was associated with increased risk for HF at both five- and ten-year follow-up (HR=1.66 [1.12-2.46] and 1.46 [1.13-1.90], respectively), which is also seen for HFpEF at five years (HR=1.72 [1.09-2.70]) and ten years (HR=1.45 [1.07-1.94]). HFrEF was not associated with inflammation for either follow-up time. CONCLUSION: Elevated inflammation early in RA diagnosis was associated HF; this association was driven by HFpEF and not HFrEF, suggesting a window of opportunity for prevention of HFpEF in RA.
34177126 Automatic chronic degenerative diseases identification using enteric nervous system images 2021 Studies recently accomplished on the Enteric Nervous System have shown that chronic degenerative diseases affect the Enteric Glial Cells (EGC) and, thus, the development of recognition methods able to identify whether or not the EGC are affected by these type of diseases may be helpful in its diagnoses. In this work, we propose the use of pattern recognition and machine learning techniques to evaluate if a given animal EGC image was obtained from a healthy individual or one affect by a chronic degenerative disease. In the proposed approach, we have performed the classification task with handcrafted features and deep learning-based techniques, also known as non-handcrafted features. The handcrafted features were obtained from the textural content of the ECG images using texture descriptors, such as the Local Binary Pattern (LBP). Moreover, the representation learning techniques employed in the approach are based on different Convolutional Neural Network (CNN) architectures, such as AlexNet and VGG16, with and without transfer learning. The complementarity between the handcrafted and non-handcrafted features was also evaluated with late fusion techniques. The datasets of EGC images used in the experiments, which are also contributions of this paper, are composed of three different chronic degenerative diseases: Cancer, Diabetes Mellitus, and Rheumatoid Arthritis. The experimental results, supported by statistical analysis, show that the proposed approach can distinguish healthy cells from the sick ones with a recognition rate of 89.30% (Rheumatoid Arthritis), 98.45% (Cancer), and 95.13% (Diabetes Mellitus), being achieved by combining classifiers obtained on both feature scenarios.
34057311 Isolation, behavioral changes and low seroprevalence of SARS-CoV-2 antibodies in patients 2021 May 31 OBJECTIVES: Patients with chronic rheumatic diseases (CRD), such as Systemic Lupus Erythematosus (SLE) and Rheumatoid Arthritis (RA), require special attention during the COVID-19 pandemic, as they are considered at risk of severe infections. We assessed the seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in patients with SLE and RA and patient behavior, disease-related symptoms, and mental health. METHODS: More than 900 participants were included: 405 patients with RA or SLE (CRD-patients) and 513 blood donors. All participants had blood SARS-CoV-2 total antibodies measured (sensitivity 96.7%, specificity 99.5%) and answered a questionnaire concerning behavior, anxiety, and symptoms of depression (PHQ-9). The CRD patients were further asked about physical activity, adherence to medication, and disease-related symptoms. RESULTS: CRD-patients had a significant lower seroprevalence of SARS-CoV-2 antibodies (n=1/365, 0.3%) compared to blood donors (n=10/513, 1.9%) (p=0.03). Almost 60% of patients were unable to exercise as usual, increased pain was experienced by 34% of patients and increased disease activity by 24%. Almost 10% of patients reduced or discontinued their immunosuppressive treatments at their own initiative. Symptoms of moderate depression were present in 19% of patients compared to 6,8% blood donors (p<0.001). CONCLUSIONS: Low seroprevalence in patients with CRDs indicates successful mitigation of exposure to SARS-CoV-2. However, this appears to occur at the expense of physical activity, experience of increased pain, disease activity, and symptoms of depression. There is a need for care providers to be aware of these negative side-effects and for further studies to investigate the possible long-term consequences.
33973407 Nurse-led consultations for patients with rheumatoid arthritis at low disease activity- a 2021 May 10 OBJECTIVE: To determine the effectiveness of nurse-led consultations in patients with stable rheumatoid arthritis (RA) in Hong Kong. METHOD: This is a single-centre, randomized, open-label, non-inferiority trial. RA patients with low disease activity (LDA) were randomized in a 1:1 ratio to nurse-led consultation or rheumatologist follow-up for 2 years. The primary endpoint was the proportion of patients who remained at LDA. Secondary endpoints included the proportion of patients in disease remission and the scores of Leeds satisfaction questionnaire (LSQ) at 2 years, changes from baseline in DAS28-CRP, modified Total Sharp Score (mTSS), Health Assessment Questionnaire-Disability Index (HAQ-DI), Short Form 36-item (SF-36) physical component score and Compliance Questionnaire of Rheumatology 19-item (CQR-19) score. RESULTS: Among 280 patients who were randomized equally to either nurse-led consultation or rheumatologist follow-up, 267 patients completed the study. 92.1% and 91.4% patients remained at LDA at 2 years in nurse-led consultation and rheumatologist follow-up group, respectively. The 95% confidence intervals (CI) of the adjusted treatment difference were within the pre-defined non-inferiority margin in both the intention-to-treat analysis (95% CI -5.75, 7.15) and the per-protocol analysis (95% CI -1.67, 7.47). Although the changes in DAS28-CRP over 2 years were significantly different between the 2 treatment groups (p<0.001), there were no significant changes from baseline in mTSS, HAQ-DI, SF-36 physical component scores and CQR-19 scores. At the end of the study, more patients expressed satisfaction with nurse-led consultations. CONCLUSION: Nurse-led consultation is not inferior to rheumatologist follow-up in patients with stable RA.
33349815 Effect of pre-exposure use of hydroxychloroquine on COVID-19 mortality: a population-based 2021 Jan BACKGROUND: Hydroxychloroquine has been shown to inhibit entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into epithelial cells in vitro, but clinical studies found no evidence of reduced mortality when treating patients with COVID-19. We aimed to evaluate the effectiveness of hydroxychloroquine for prevention of COVID-19 mortality, as opposed to treatment for the disease. METHODS: We did a prespecified observational, population-based cohort study using national primary care data and linked death registrations in the OpenSAFELY platform, which covers approximately 40% of the general population in England, UK. We included all adults aged 18 years and older registered with a general practice for 1 year or more on March 1, 2020. We used Cox regression to estimate the association between ongoing routine hydroxychloroquine use before the COVID-19 outbreak in England (considered as March 1, 2020) compared with non-users of hydroxychloroquine and risk of COVID-19 mortality among people with rheumatoid arthritis or systemic lupus erythematosus. Model adjustment was informed by a directed acyclic graph. FINDINGS: Between Sept 1, 2019, and March 1, 2020, of 194 637 people with rheumatoid arthritis or systemic lupus erythematosus, 30 569 (15·7%) received two or more prescriptions of hydroxychloroquine. Between March 1 and July 13, 2020, there were 547 COVID-19 deaths, 70 among hydroxychloroquine users. Estimated standardised cumulative COVID-19 mortality was 0·23% (95% CI 0·18 to 0·29) among users and 0·22% (0·20 to 0·25) among non-users; an absolute difference of 0·008% (-0·051 to 0·066). After accounting for age, sex, ethnicity, use of other immunosuppressive drugs, and geographical region, no association with COVID-19 mortality was observed (HR 1·03, 95% CI 0·80 to 1·33). We found no evidence of interactions with age or other immunosuppressive drugs. Quantitative bias analyses indicated that our observed associations were robust to missing information for additional biologic treatments for rheumatological disease. We observed similar associations with the negative control outcome of non-COVID-19 mortality. INTERPRETATION: We found no evidence of a difference in COVID-19 mortality among people who received hydroxychloroquine for treatment of rheumatological disease before the COVID-19 outbreak in England. Therefore, completion of randomised trials investigating pre-exposure prophylactic use of hydroxychloroquine for prevention of severe outcomes from COVID-19 are warranted. FUNDING: Medical Research Council.
34205377 Distinct Roles of Vav Family Members in Adaptive and Innate Immune Models of Arthritis. 2021 Jun 19 Genetic evidence suggests that three members of the VAV family (VAV1, VAV2 and VAV3) of signal transduction proteins could play important roles in rheumatoid arthritis. However, it is not known currently whether the inhibition of these proteins protects against this disease and, if so, the number of family members that must be eliminated to get a therapeutic impact. To address this issue, we have used a collection of single and compound Vav family knockout mice in experimental models for antigen-dependent (methylated bovine serum albumin injections) and neutrophil-dependent (Zymosan A injections) rheumatoid arthritis in mice. We show here that the specific elimination of Vav1 is sufficient to block the development of antigen-induced arthritis. This protection is likely associated with the roles of this Vav family member in the development and selection of immature T cells within the thymus as well as in the subsequent proliferation and differentiation of effector T cells. By contrast, we have found that depletion of Vav2 reduces the number of neutrophils present in the joints of Zymosan A-treated mice. Despite this, the elimination of Vav2 does not protect against the joint degeneration triggered by this experimental model. These findings indicate that Vav1 is the most important pharmacological target within this family, although its main role is limited to the protection against antigen-induced rheumatoid arthritis. They also indicate that the three Vav family proteins do not play redundant roles in these pathobiological processes.
34957623 Personal healthcare costs borne by younger people living with arthritis in Australia: An e 2021 Dec 26 Arthritis is a long-term musculoskeletal disease, requiring ongoing management. However, the financial burden of managing arthritis is under-explored and is yet to be quantified from the perspective of individuals with the condition. Using an exploratory observational design, this study aimed to quantify arthritis-related costs borne by a sample of working-age adults aged 18-50 years who responded to the study advertisement. Participants completed a weekly cost diary for 6 weeks, detailing their personal non-reimbursed (out-of-pocket) arthritis-related costs. Financial distress was measured using the InCharge Financial Distress/Financial Well-Being Scale. Costs data were analysed descriptively. Mann-Whitney U tests were used to examine relationships between residential location or employment status and out-of-pocket costs. Linear regression and Spearman's rho were used to estimate relationships between age or years since diagnosis and out-of-pocket costs, and between out-of-pocket costs and financial distress respectively. Sixteen adults (median age 40 years, 100% female) with a range of arthritis conditions (median (IQR): 8 (7.5) years since diagnosis) including rheumatoid arthritis, osteoarthritis, psoriatic arthritis, and ankylosing spondylitis completed the six-week cost diary. All participants reported out-of-pocket expenditure related to arthritis. The median per-person expenditure across the 6 weeks was AUD 1635. The highest reported costs per participant across the 6 weeks were for medical expenses (median AUD 197) and allied health appointments (median AUD 190). In total, the cohort spent AUD 15,272 across the study period. Perceived financial distress was high: median (IQR) financial distress 7 (2.25) on a 1 (lowest) to 10 (highest) scale. Positive relationships between age and costs, and between costs and financial distress were identified. These findings help us understand fiscal expenditure and related distress relevant to younger individuals with arthritis, and can be used to raise awareness of their financial concerns.
34060659 Therapeutic potential of targeted-gold nanospheres on collagen-induced arthritis in rats. 2021 Oct Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that causes functional disability due to bone destruction and severe joint pain. Current anti-rheumatic treatments develop severe complications and do not provide complete remission. Gold nanoparticles (AuNPs) have garnered attention because of their unique physical and chemical properties. In this study, we have evaluated the therapeutic effects of gold nanospheres (AuNSs) with two different ligands (targeted-nanoparticles) against collagen-induced arthritis (CIA) and compared the outcomes with conventional methotrexate (MTX) and biological (infliximab) treatments. Clinical evaluation was performed by radiographic and histological examinations. The bioaccumulation of AuNSs in vital organs was assessed. The mechanistic studies targeting pro-inflammatory/anti-inflammatory and angiogenic mediators' expressions were performed. Radiographic examination showed that the targeted AuNSs reduced joint space narrowing and bone erosion. Moreover, histopathological examination of rat ankle joints demonstrated that targeted AuNSs reduce bone and cartilage degeneration/inflammation. Gold nanospheres-conjugated with nucleus localized peptide (nuclear membrane-targeted) (AuNSs@NLS) has resolved bone destruction and inflammation compared to gold nanospheres-conjugated at polyethylene glycol (AuNSs@PEG). Although the AuNSs accumulated in different organs in both cases, they did not induce any toxicity or tissue damage. The two different targeted AuNSs significantly suppress inflammatory and angiogenic mediators' expression and induced anti-inflammatory cytokine production, but the AuNSs@NLS had superior therapeutic efficacy. In conclusion, these results suggested that nuclear membrane-targeted AuNSs effectively attenuated arthritis progression without systemic side effects.
34984145 Diagnostic Dilemma of Paraneoplastic Rheumatic Disorders: Case Series and Narrative Review 2021 Nov Paraneoplastic rheumatic disorder (RD) is a disorder that may present before, concurrent with, or after the diagnosis of malignancy. Paraneoplastic RDs are a clinical expression of occult cancer that is not directly related to a tumor or metastasis and manifests as rheumatoid symptoms. The RD is determined by the organ system affected by articular, muscular, cutaneous, vascular, or miscellaneous symptoms. Each case is challenging to diagnose because cancer may present with similar symptoms as a common rheumatic disorder. Of note, the majority of cases have minimal responsiveness or no responsiveness to standard rheumatoid treatment. Therefore, it is imperative to recognize and treat the underlying cancer accordingly. Herein, we present four different diagnostic dilemma cases of RD: case #1 - leukocytoclastic vasculitis and C3 glomerulopathy, case #2 - scleroderma, case #3 - Raynaud's syndrome and possible lupus-like syndrome, and case #4 - inflammatory myositis. Institutional IRB approval was obtained for this case series. We will discuss and review the literature on each topic. In addition, we will mention a review of paraneoplastic rheumatoid arthritis. As rheumatic disease is associated with the use of immune checkpoint inhibitors (ICIs) for cancer treatment, we will briefly discuss some of the most common rheumatic presentations in the setting of these drugs. This case review aims to inform clinicians about the atypical presentation of paraneoplastic RD and to highlight the need for interdisciplinary management between rheumatologists, oncologists, and primary care practitioners.
34703142 A case of progressive systemic sclerosis/lupus overlap syndrome: Presenting with parotid s 2021 May An overlap syndrome is a medical condition which shares features of at least two more widely recognized disorders. Autoimmune connective tissue diseases include systemic lupus erythematosus (SLE), scleroderma, polymyositis, dermatomyositis, rheumatoid arthritis and Sjögren's syndrome where overlap syndrome most commonly seen in combination with SLE and systemic sclerosis (SSc). Sjogren's is an autoimmune exocrinopathy, in which systemic diseases such as arthritis, interstitial lung disease and renal disease may develop in addition to the pathognomonic features such as dry eyes and mouth. The other associated disease with Sjogren's includes sialadenitis. Sialadenitis of the parotid gland is one of the major disorders of salivary gland. This article presents a rare case report of a patient diagnosed with sialadenitis of the parotid gland and associated with progressive SSc/lupus overlap syndrome and secondary Sjogren's.
34434965 Impact of the Host-Microbiome on Osteomyelitis Pathogenesis. 2021 The microbiome is a collection of genomes from microbiota, including all microorganisms in a niche, through direct and indirect interactions with the host. Certain microorganisms can exist in areas conventionally considered to be sterile, such as the bone matrix. Osseous microbiota dysbiosis caused by host-microbiome perturbation or external infections may ultimately lead to osteomyelitis, a bone inflammatory disorder. Our review covers the current discoveries on the impact of host-microbiome on osteomyelitis and some common osseous diseases. Some studies suggest that the microbiotas from both osseous and non-osseous tissues (e.g., blood or gut) impact the pathogenicity of osteomyelitis and other osseous diseases (e.g., rheumatoid arthritis). We believe that this review will provide readers with a better understanding on the role of the microbiome to the host's bone health.
34540335 Idiopathic Anaphylaxis: A Diagnosis of Exclusion. 2021 Jan We report the case of a 67-year-old female with hypertension and rheumatoid arthritis who had 5 unprovoked episodes of anaphylaxis in an 18-month period of time. We review idiopathic anaphylaxis, including its definition, diagnostic work-up, and differential diagnosis.
31869185 Sternoclavicular Joint Infection. 2022 Jan The sternoclavicular joint is a saddle-shaped diarthrodial joint that joins the upper extremity appendicular skeleton to the axial skeleton. The large medial clavicle articulates with the superomedial manubrium and costal cartilage of the first rib, forming a joint with very little bony stability. Within the joint is an intra-articular disc ligament composed of dense fibrous cartilage that provides structural support and prevents medial displacement of the clavicle. The surrounding robust costoclavicular ligament and capsule offers an added layer of support. The primary restraints to anterior and posterior translation of the joint are the anterior and posterior sternoclavicular ligaments. Despite these restrictions, the sternoclavicular joint is actually very mobile and moves more than 30 degrees in the axial and coronal planes while having more than 45 degrees of rotation. Functionally, it is quite similar to other amphiarthroses, such as the sacroiliac joint or pubic symphysis. Blood supply to the joint comes from the articular branches of the suprascapular and internal thoracic arteries. The nerve to the subclavius muscle and the medial suprascapular nerves provide innervation to the sternoclavicular joint. Septic arthritis of the sternoclavicular joint is rare and represents less than 1% of all bone and joint infections. A sternoclavicular joint infection is, in the majority of cases, associated with other systemic illnesses and/or general poor health status. Common concurrent issues include diabetes, intravenous drug use, immunosuppression, and rheumatoid arthritis. While rare, prompt diagnosis and treatment are essential to prevent spread into the posteriorly located great vessels, mediastinum, and pleural space.
35145344 Perception of Biosimilar Biologics and Non-Medical Prescription Switching among Rheumatolo 2022 Jan BACKGROUND: The aim of this study was to evaluate rheumatologists' perceptions of biosimilar biologics and Non-Medical Switching (NMS). METHODS: A cross-sectional survey was conducted among registered members of the Saudi Society for Rheumatology. The questionnaire focused on biosimilars and NMS. Logistic regression was performed to ascertain the effect of demographics and practice characteristics on the use of biosimilars and NMS. RESULTS: Out of 249 SSR members, 143 completed the survey, generating a response rate of 57.4%. Of those (59.44%) were men with a mean (±SD) age and years of practice of 42.3 ± 9.13 and 10.3 ± 8.9, respectively. Rheumatologists managing adult patients (81.82%) and Ministry of Health practice (43.36 %) were the majority of respondents. Previous experience in prescribing a biosimilar was reported by 43 (30.07%) participants, with a higher probability among women (p = 0.015). A total of 26 (18.18%) participants had performed NMS on eligible patients. Adequate knowledge on biosimilars was reported by 69 (48.25%) participants. The adequacy of evidence to grant biosimilar approval for the studied indication and extrapolation to treat other conditions was reported by 88 (61.5%) and 69 (48.3%), respectively. The concept of totality-of-the-evidence was well understood by 37.1%. Biosimilars had been previously used by 43 (30.07) participants in their practice. NMS had been attempted by 26 (18.18), while 86 (60.1%) participants believed that NMS might harm patients. CONCLUSION: There is a clear knowledge gap about the biosimilar approval process among adult and pediatric rheumatologists who took part in the survey. In addition, a large number of participants reported having negative opinions about NMS. There is a need to organize SSR-led educational activities, and develop national guidelines regarding biosimilars and NMS.
34831143 The Role of Glucocorticoids in Inflammatory Diseases. 2021 Oct 28 For more than 70 years, glucocorticoids (GCs) have been a powerful and affordable treatment option for inflammatory diseases. However, their benefits do not come without a cost, since GCs also cause side effects. Therefore, strong efforts are being made to improve their therapeutic index. In this review, we illustrate the mechanisms and target cells of GCs in the pathogenesis and treatment of some of the most frequent inflammatory disorders affecting the central nervous system, the gastrointestinal tract, the lung, and the joints, as well as graft-versus-host disease, which often develops after hematopoietic stem cell transplantation. In addition, an overview is provided of novel approaches aimed at improving GC therapy based on chemical modifications or GC delivery using nanoformulations. GCs remain a topic of highly active scientific research despite being one of the oldest class of drugs in medical use.
34622156 Once-monthly hemin suppresses inflammatory and autoreactive CD4(+) T cell responses to ro 2021 Oct 22 Rheumatoid arthritis (RA) is an inflammatory autoimmune disease that would permanently damage the affected joints. Unfortunately, a large proportion of RA patients fail to respond adequately to current treatments. Here, repurposing hemin and its ultra-long-acting formulation were explored for the effective treatment of RA in animal models. We provided evidence that hemin prevented the onset and ameliorated the clinical course of RA. Notably, hemin treatment rescued the dysregulated gene expression in animal models of RA, resulting in attenuation of Th1/Th17 cell-mediated responses and proinflammatory cytokines. Moreover, we further formulated hemin into the in-situ forming implant, and a single injection of the ultra-long-acting hemin exerted potent disease-modifying effects for at least six weeks with a remarkable dose reduction. Taken together, given the potent anti-inflammatory and immunosuppressive effects, the once-monthly hemin injection holds promise for rapid clinical translation, and represents a potential strategy to treat RA and possibly other autoimmune diseases.
34059186 In vitro effect of biological and conventional disease-modifying antirheumatic drugs on fi 2021 Oct OBJECTIVE: Fibrocytes are circulating bone-marrow-derived cells that migrate to organs with ongoing repair or inflammation. In the target organ, the cells differentiate, become long and spindle-shaped, and are able to produce extracellular matrix components. In fibrotic diseases, the levels of fibrocytes are increased, both in circulation and the diseased tissue. In rheumatoid arthritis (RA), fibrocytes have been proposed to be involved in the spread of the disease and possibly in RA fibrotic manifestations, as can be seen in RA interstitial lung disease (RA-ILD). Therefore, we aimed to investigate a range of current RA treatment modalities (corticosteroids and conventional and biological disease-modifying antirheumatic drugs (DMARDs)) regarding their effect on in vitro fibrocyte differentiation. METHODS: A total of 10 participants were included (5 patients with RA and 5 healthy controls). Peripheral blood mononuclear cells (PBMCs) were isolated and cultured for 5 days with prednisolone, conventional DMARDs (methotrexate, sulfasalazine, and hydroxychloroquine), and biological DMARDs (etanercept, tocilizumab, adalimumab, abatacept, and rituximab). The numbers of fibrocytes were counted. Dose-response data for abatacept and tocilizumab were collected. RESULTS: Abatacept and prednisolone significantly suppressed differentiation of PBMC into fibrocytes compared with control (p=0.02 and p<0.01, respectively) (n=10). In overall analysis (n=10), abatacept reduced fibrocyte levels with an average of 44% overall and 71% in the RA group compared with the control wells. Tocilizumab reduced the fibrocyte count by 63% overall and 45% in the RA group, although it was not significant (p=0.07 and p=0.06, respectively). Both tocilizumab and abatacept display a dose-response relationship. CONCLUSION: Abatacept and prednisolone suppress the differentiation of mononuclear cells to mature fibrocytes in vitro in patients with RA, and data indicate a similar effect of tocilizumab; this was further supported by the observed dose-response relationship. Clinical trials are needed to compare the effect of these drugs on fibrotic RA manifestations, for example, RA-ILD.
33436077 The role of vitamin D in autoimmune diseases: could sex make the difference? 2021 Jan 12 Over the last decades, a central role for vitamin D in immune modulation has been well established. The active form of vitamin D, i.e., 1,25-dihydroxyvitamin D, through the interaction with vitamin D receptor, exerts different activities on the innate and adaptive immune system, among which suppression of inflammation and promotion of tolerogenic responses. Vitamin D insufficiency has been linked to autoimmune disorders that commonly display significant differences between females and males due to genetic, epigenetic, hormonal, and environmental factors. Notably, a number of studies recently showed a cross-talk between vitamin D and the sex hormone estrogen. Estrogen-mediated effects on immune response may favor a Th1 profile or a Th2 profile, depending on hormone concentration. Thus, estrogen-mediated effects appear to be variable on autoimmunity depending on its concentration but also on the pathogenic mechanisms underlying the different autoimmune diseases (i.e., Th1- or Th2-mediated diseases). Notably, estrogen has been demonstrated to enhance vitamin D function favoring its accumulation, and increasing the expression of vitamin D receptor, thus resulting in a more potent anti-inflammatory response in females than males. On the other hand, vitamin D has been shown to downregulate in immune cells the expression of aromatase, which converts testosterone to estrogen, leading to a decrease in estrogen level. Overall, available data allow us to hypothesize a higher protective effect of vitamin D-based therapeutic approaches in women, at least in fertile age, than in men. Future studies are needed to expand current knowledge on the immunomodulatory role of vitamin D in a sex and gender perspective, paving the way to a more personalized therapeutic approach in autoimmune diseases.