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ID PMID Title PublicationDate abstract
33568685 Bee venom phospholipase A2 alleviates collagen-induced polyarthritis by inducing Foxp3(+) 2021 Feb 10 The mechanism underlying bee venom (BV) therapy is still controversial, with opinions ranging from constituent-based pharmacological action to homeopathic-like activity. The purpose of this study was to examine whether BV phospholipase A2 (bvPLA2), an enzymatic component of BV, is a novel anti-inflammatory and anti-arthritic mediator capable of stimulating CD25(+) Foxp3(+) regulatory T cell (Treg) polarization in a mouse model of human rheumatoid arthritis (RA). An experimental model of RA was established in male DBA/1 mouse by 2-week-interval injections of 100 μg type II collagen emulsified in complete (first injection) or incomplete Freund's adjuvant (second injection) at the base of the tail. During arthritis development, bvPLA2 (0.1, 0.5, 1.0 mg/kg) and/or Treg inhibitors such as anti-CD25 antibodies and peptide 60 (P60) were injected intraperitoneally for 5 weeks. Arthritic symptoms and the expansion of Tregs were then assessed by behavioral assessments, histological and micro-CT imaging, and flow cytometry. bvPLA2 injections significantly alleviated arthritic behaviors such as squeaking and joint swelling, consistent with changes seen on both histological and micro-CT images. The anti-arthritic effects of bvPLA2 were blocked by intraperitoneal injections of 0.25 mg/kg anti-CD25 antibody and 10 μg/kg P60, as determined by behavioral assessments. Flow cytometric analysis of dendritic cells, B cells, and major T cell subsets from spleens revealed a significant depletion of Tregs following anti-CD25 antibody, but not P60, treatment. bvPLA2 treatment exerted significant anti-inflammatory and anti-arthritic activities in a mouse model of RA via the induction of Tregs.
34580174 It is not just about sex: viewpoints of men with inflammatory arthritis on the overall imp 2021 Sep OBJECTIVES: Sexual health is defined as a state of physical, emotional, mental and social well-being in relation to sexuality. The impact of inflammatory arthritis (IA) on male sexual health has been mainly studied focusing on erectile function, one of the physical components of sexual health. Our objective was to describe the viewpoints among men with IA in the Netherlands on the overall impact of IA on their sexual health. METHODS: Q-methodology, a mixed methods approach to systematically study subjectivity was used. Adult men diagnosed with IA ranked 34 opinion statements about potential impacts of IA on their sexual health and were interviewed. By-person factor analysis was used to identify common patterns in the rankings, which were interpreted as viewpoints. Data from the interviews were used to verify and adjust the interpretations. RESULTS: 30 men (22-77 years) with IA were included. The analysis revealed three viewpoints. Men with the viewpoint 'Arthritis negatively affects my sexual health' experience a dramatic impact on all components of sexual health. In viewpoint 'I am keeping up appearances', IA negatively impacts sexual health but a distinguishing coping mechanism could mask a more serious negative impact. Men with the viewpoint 'I am satisfied with my sexual health'' experience no significant impact of IA on their sexual health. CONCLUSIONS: We identified three viewpoints on the impact of IA on male sexual health, two revealed a negative influence that goes beyond the physical act of sex. IA can severely affect the emotional, mental and social components of sexual health.
34288565 Combinations of Anticyclic Citrullinated Protein Antibody, Rheumatoid Factor, and Serum Ca 2021 Oct OBJECTIVE: To evaluate the prevalence of elevations of anti-cyclic citrullinated peptide-3 (anti-CCP3) antibody, rheumatoid factor IgM (RF-IgM) and serum calprotectin (sCP) in pre-rheumatoid arthritis (RA) as well as the diagnostic accuracies of these biomarkers for the timing of diagnosis of future RA. METHODS: A total of 215 RA cases, each with approximately three pre-RA diagnoses and one post-RA diagnosis serum sample, and controls were identified from the Department of Defense Serum Repository. All case samples and a single sample from each control subject were tested for anti-CCP3 (IgG), RF-IgM, and sCP. The diagnostic accuracies of biomarkers for future RA were evaluated. RESULTS: Anti-CCP3, RF-IgM, and sCP were elevated in pre-RA, with anti-CCP3 and sCP significantly elevated compared with RF-IgM at the earliest time points. Within the cases, the combination of anti-CCP3 and RF-IgM positivity had a positive predictive value (PPV) of 35.6% for a diagnosis of RA in 3 years or less, which is significantly higher than the PPV of 18.7% for anti-CCP3 positivity alone (P < 0.001). A combination of anti-CCP3, RF-IgM, and sCP had the highest PPV (53.0%) for a diagnosis of RA in 3 years or less; however, this was not significantly higher than the PPV for anti-CCP3 and RF-IgM positivity (P = 0.248). CONCLUSION: Anti-CCP3, RF-IgM, and sCP are elevated in pre-RA; furthermore, combinations of elevations of these biomarkers are more commonly seen in the period of less than or equal to 3 years to diagnosis. This may be considered in creating inclusion criteria in prevention trials in RA. In addition, the biologic relationships of these biomarkers in pre-RA need exploration.
34481308 Microstructure and mechanical behaviors of tibia for collagen-induced arthritic mice treat 2021 Dec Rheumatoid arthritis (RA) is a systemic polyarticular arthritis that primarily affects the small joints but also causes bone erosion in large joints. None of the currently existing treatment approaches is curable. In this study, the effects of human gingiva-derived mesenchymal stem cells (GMSCs) on collagen-induced arthritis (CIA) mice are examined by experimentally assessing the microstructure and mechanical behaviors of tibia. Bone morphology and mineral density of mouse tibiae were assessed using micro-X-ray computed tomography (micro-CT). Compression testing was performed on mouse tibia to access its stiffness. The deformation and strain localized inside proximal tibia were mapped using mechanical testing coupled with micro-CT and digital volume correlation of micro-CT images. The results show that CIA disease caused bone erosion in epiphyseal cortical bone, which manifested into the adjacent epiphyseal trabecular bone, and also affected the metaphyseal cortical bone. CIA disease also weakened the load-bearing function of proximal tibia. GMSC treatment interfered with the progress of CIA, attenuated the bone erosion in epiphyseal and metaphyseal trabecular bone and resulted in improved load-bearing function of proximal tibia. GMSCs provide a promising potential treatment of autoimmune arthritis.
34398520 Activation of Hypothalamic AMP-Activated Protein Kinase Ameliorates Metabolic Complication 2022 Feb OBJECTIVE: To investigate whether thermogenesis and the hypothalamus may be involved in the physiopathology of experimental arthritis (EA). METHODS: EA was induced in male Lewis rats by intradermal injection of Freund's complete adjuvant (CFA). Food intake, body weight, plasma cytokines, thermographic analysis, gene and protein expression of thermogenic markers in brown adipose tissue (BAT) and white adipose tissue (WAT), and hypothalamic AMP-activated protein kinase (AMPK) were analyzed. Virogenetic activation of hypothalamic AMPK was performed. RESULTS: We first demonstrated that EA was associated with increased BAT thermogenesis and browning of subcutaneous WAT leading to elevated energy expenditure. Moreover, rats experiencing EA showed inhibition of hypothalamic AMPK, a canonical energy sensor modulating energy homeostasis at the central level. Notably, specific genetic activation of AMPK in the ventromedial nucleus of the hypothalamus (a key site modulating energy metabolism) reversed the effect of EA on energy balance, brown fat, and browning, as well as promoting amelioration of synovial inflammation in experimental arthritis. CONCLUSION: Overall, these data indicate that EA promotes a central catabolic state that can be targeted and reversed by the activation of hypothalamic AMPK. This might provide new therapeutic alternatives to treat rheumatoid arthritis (RA)-associated metabolic comorbidities, improving the overall prognosis in patients with RA.
34557621 Partners of female patients with rheumatoid arthritis and reproductive decision-making: a 2021 OBJECTIVE: Partners of patients with RA often take on supportive roles given the debilitating nature of RA. Our objective was to explore the perspectives, attitudes and experiences of partners of female patients with RA regarding reproductive experiences and decision-making. METHODS: We conducted a qualitative study involving semi-structured interviews with partners of female patients with RA. We defined a partner as an individual within a romantic relationship. Constructivist grounded theory was applied to interview transcripts to identify and conceptualize themes. RESULTS: We interviewed 10 partners of female patients with RA (10 males; mean age, 35 [23-56] years), of whom 40% had at least one child with a female patient with RA and did not desire additional children. We identified four themes representing stages of reproductive decision-making: (1) developing an understanding of RA, (2) contemplating future family decision-making, (3) initiating reproductive decision-making with partner, and (4) reflecting on past reproductive experiences. Participants contemplated their attitudes and perspectives regarding pregnancy and used available information to support their partner's medication decisions. When reflecting on their reproductive experiences, participants shared the impacts of past reproductive decisions on their romantic relationship and their mental health and wellbeing. CONCLUSION: Our study highlights the need for comprehensive support for both female patients with RA and their partners at all stages of reproductive decision-making. Health-care providers can identify opportunities for intervention that involves female patients with RA and their partners to minimize stress and its negative impacts on the family.
34485342 Residual Pain in the Context of Selecting and Switching Biologic Therapy in Inflammatory R 2021 For many years, inflammatory rheumatic diseases (IRDs) represented a source of disappointment in medical care caused by the mediocre efficacy of the available treatments. Some of these diseases, like Rheumatoid Arthritis (RA) or Ankylosing Spondylitis (AS), caused fear in the general population, especially due to associated joint deformities and subsequent disabilities. However, in the last 20 years, a new successful class of antirheumatic drugs has become available: biologic Disease-Modifying Antirheumatic Drugs (bDMARDs). Due to this innovative treatment, the days are over when joint and spine deformities defined the condition of a person with RA or AS. Nonetheless, expectations are higher today, and other clinical problems, (not entirely solved by bDMARDs), seem to drive the drug selection during the span of rheumatic diseases. Most of these issues are covered by the term "unmet needs." One of the most intriguing of such needs is the residual pain (RP) in patients that are otherwise in the biological remission of the disease. Present in a significant proportion of the patients that enter remission status, RP is poorly understood and managed. In recent years, new data has become available in this area and new conceptual clarifications have occurred. In this review, we explain the various nature of RP and the necessity of treatment diversification in such situations. All in all, we believe this condition is far more complex than simple pain and includes other clinical aspects, too (like fatigue or mood changes) so the terms Post-Remission Syndrome (PRS), and PRS pain might be more appropriate.
33912248 Prevalence, therapy and tumour response in patients with rheumatic immune-related adverse 2021 BACKGROUND: Immune checkpoint inhibitors (ICIs) improved cancer therapy by inducing a higher immune system activity. This effect can cause rheumatic immune-related adverse events (rh-irAEs), which have not yet been extensively studied. METHODS: We analysed 437 patients between 2014 and 2019, treated with ipilimumab (anti-CTLA-4) and/or nivolumab (anti-PD-1) or pembrolizumab (anti-PD-1) at the Clinic for Internal Medicine III, Oncology, Haematology and Rheumatology at the University Hospital Bonn, Germany. RESULTS: Of the 437 patients 60% were males. Patients were mainly treated for melanoma, lung cancer, head and neck tumour and urothelial carcinoma. At least one immune-related adverse event (irAE) was observed in 163 patients (37.3%), including rh-irAE. Most common side effects were rash, colitis and hepatitis. We identified 19 patients (4.3%) with a minimum of one rh-irAE due to ICI therapy; three of those had a pre-existing rheumatic disease. Arthralgia developed most frequently in eight patients (42.1%). Other rh-irAEs were: arthritis (n = 7; distinguished in rheumatoid arthritis, psoriatic arthritis, juvenile idiopathic arthritis and undifferentiated arthritis), myalgia (n = 2) and myositis (n = 3). Most rh-irAEs were classified as moderately severe (Common Terminology Criteria of Adverse Events grade 2: 68.4%). Median time between starting ICI therapy and the occurrence of rh-irAE was 109 days (interquartile range 40-420 days). Fifteen patients (78.9%) were treated with glucocorticosteroids. In four cases additional therapy with methotrexate or tocilizumab was required. Even though patients benefited from ICI treatment, therapy had to be discontinued in six of the participants due to rh-irAE. Interestingly, patients with rh-irAE had a significantly higher tumour response compared with patients without rh-irAE (94.4% versus 43.5%; p < 0.0001). CONCLUSION: Rh-irAEs occur under ICI therapy, especially in patients with higher tumour response. However, they are not the most frequent irAE after ICI exposure: 9.3% of all irAEs were rheumatic (20 rh-irAE cases in 19 patients of a total of 215 irAE cases in 163 patients).
34462459 T-bet represses collagen-induced arthritis by suppressing Th17 lineage commitment through 2021 Aug 30 T-bet is a key transcription factor for the T helper 1 lineage and its expression level is negatively correlated to inflammation in patients with rheumatoid arthritis (RA). Our previous study using T-bet transgenic mice revealed over-expression of T-bet completely suppressed collagen-induced arthritis (CIA), a murine model of RA, indicating a potential suppressive role of T-bet in the pathogenesis of autoimmune arthritis. Here, we show T-bet-deficiency exacerbated CIA. T-bet in CD4 + T cells, but not in CD11c + dendritic cells, was critical for regulating the production of IL-17A, IL-17F, IL-22, and TNFα from CD4 + T cells. T-bet-deficient CD4 + T cells showed higher RORγt expression and increased IL-17A production in RORγt-positive cells after CII immunization. In addition, T-bet-deficient naïve CD4 + T cells showed accelerated Th17 differentiation in vitro. CIA induced in CD4-Cre T-bet(fl/fl) (cKO) mice was more severe and T-bet-deficient CD4 + T cells in the arthritic joints of cKO mice showed higher RORγt expression and increased IL-17A production. Transcriptome analysis of T-bet-deficient CD4 + T cells revealed that expression levels of Th17-related genes were selectively increased. Our results indicate that T-bet in CD4 + T cells repressed RORγt expression and function resulting in suppression of arthritogenic Th17 cells and CIA.
35224553 The Use of Consumer Wearable Physical Activity Monitors in Clinical Populations with Funct 2021 Functionally limiting health conditions have a high rate of prevalence worldwide and incur a significant amount of economic burden. Physical activity (PA) can prevent the onset of these conditions and alleviate economic burden by reducing symptoms, but a large portion of these individuals do not engage in health enhancing PA. Consumer wearable physical activity monitors (WPAM) are tools that have become increasingly popular within the past few years and could provide a means to improve PA levels for individuals with health conditions that cause functional limitations. This review reports on the validity of PA outcomes, feasibility and utility, and intervention/promotion effectiveness for consumer WPAM in functionally limited clinical populations. 2250 records from January 2018 to July 2021 were retrieved from PubMed, Web of Science, SPORTDiscus and CINAHL with 656 records being duplicates and 23 records passing a full-text article review. Studies included within the review looked at individuals with osteoarthritis, rheumatoid arthritis, axial spondyloarthritis, multiple sclerosis, Parkinson's disease, ischemic stroke and peripheral arterial disease. The most popular brand of consumer WPAM was Fitbit. Validation studies for consumer WPAM were primarily focused on step counts showing overestimations for daily step counts and over- and under-estimations occurring within shorter time durations depending on step cadence. Wrist worn WPAM are the most feasible for functionally limited clinical populations with widespread utilization for associating clinically relevant outcomes with PA levels but they have limited validation to confirm their accuracy and precision in measurement. Interventions included used a mixture of a WPAM and other behavior change techniques to improve PA levels for clinical populations and show promising effectiveness. Future work is warranted on determining the validity of PA outcomes from WPAM determined to be feasible in select clinical populations and creating interventions looking at which features of a consumer WPAM intervention promote PA.
34380400 A Modified Extensor Carpi Ulnaris Tenodesis with the Sauvé-Kapandji Procedure. 2021 Sep Background: Since the Sauvé-Kapandji procedure was introduced in 1936, many modifications were created using dynamic stabilizer, such as the ECU (extensor carpi ulnaris), the FCU (flexor carpi ulnaris), pronator teres to solve proximal ulnar stump pain. We believe that this modification is also another option for distal ulnar stump instability. Methods: From January 1998 to February 2017, there were 13 patients received the Sauvé-Kapandji (S-K) procedure with tenodesis of the ECU to the carpus and interosseous membrane. The average age at operation was 52 years (range, 28 to 63 years). Four had traumatic arthritis (two from distal radial fracture malunion, two had instability of distal radioulnar joint from Essex-Lopresti injury), four had primary osteoarthritis of the distal radio-ulnar joint, two had rheumatoid arthritis, one had gouty arthritis, two had madelung deformity. The average follow-up was 30 months (range, 15 to 72 months). Results: Postoperative pronation/supination of the forearm had significantly improved with the exception of the wrist flexion/extension. After surgery, the mean radioulnar distance was narrowed from 11 mm to 9 mm, but no significant difference in 12 patients. All patients had improved in wrist pain, 10 patients had no pain and 3 patients with mild pain over the distal ulnar stump. The mean grip strength had significantly improved from 51% of the contralateral side to 75%. The lateral and stress X-ray films showed no instability of the distal ulnar stump after surgery. Conclusions: In conclusion, the modified S-K procedure using the tenodesis of ECU provides a multi-directional stability and is a reliable surgical procedure for distal radioulnar disorders.
34020693 Tofacitinib downregulates antiviral immune defence in keratinocytes and reduces T cell act 2021 May 21 BACKGROUND: Tofacitinib is a novel Janus kinase (JAK) inhibitor approved for the treatment of rheumatoid arthritis, psoriatic arthritis, and ulcerative colitis. In clinical trials, the most common adverse events observed were nasopharyngitis, upper respiratory tract infections, and zoster. JAKs are found downstream of the type II cytokine receptor family used by a number of T(H)17 cell-associated cytokines for signal transduction. These cytokines lead to the secretion of antiviral and antimicrobial peptides (AMPs) by keratinocytes or synoviocytes. Blocking the JAK pathway might result in a diminished secretion of antimicrobial and antiviral peptides causing higher susceptibility to infections in patients treated with JAK inhibitors. METHODS: We treated primary human keratinocytes and synoviocytes with tofacitinib and subsequently added various cytokines and bacterial surface proteins before evaluation of the response via RT-qPCR. CD69 expression on tofacitinib-treated PBMCs was investigated via flow cytometry. RESULTS: We found a markedly reduced gene expression of all tested antiviral peptides such as MX1 or ISG15 in keratinocytes and synoviocytes in the presence of tofacitinib in vitro. Additionally, we found that JAK inhibition reduced activation of T cells after stimulation with bacterial LPS or viral VZV gE. CONCLUSIONS: The antiviral immunity is strongly inhibited in the presence of tofacitinib in vitro, while the antimicrobial immunity does not seem to be affected. In T cells, the overall activation process seems to be influenced by tofacitinib. These findings suggest that tofacitinib has an impact on antiviral immunity such as patients treated with tofacitinib often show adverse events like herpes zoster.
33986966 COVID-19: An Emerging Culprit of Inflammatory Arthritis. 2021 Arthralgia is one of the most common symptoms that occur in patients with COVID-19. About 15% of patients present with arthralgia at some point. Although COVID-19 seems to attack the musculoskeletal system (muscles and joints) in its infective and postinfective stage causing inflammatory arthritis, not much is known about the rheumatic manifestations of this infection. In this case series of 5 patients, we discuss the occurrence of bilaterally symmetrical polyarthritis in patients, previously free from any rheumatic disease, after encountering COVID-19 infection. The musculoskeletal manifestations in these patients phenotypically resembled rheumatoid arthritis. These patients were treated successfully with low-dose glucocorticoids and disease-modifying antirheumatic drugs (DMARDs).
34407179 Adherence to self-administered biologic disease-modifying antirheumatic drugs across healt 2021 Nov 23 PURPOSE: Adherence to self-administered biologic disease-modifying antirheumatic drugs (bDMARDs) is necessary for therapeutic benefit. Health-system specialty pharmacies (HSSPs) have reported high adherence rates across several disease states; however, adherence outcomes in rheumatoid arthritis (RA) populations have not yet been established. METHODS: We performed a multisite retrospective cohort study including patients with RA and 3 or more documented dispenses of bDMARDs from January through December 2018. Pharmacy claims were used to calculate proportion of days covered (PDC). Electronic health records of patients with a PDC of <0.8 were reviewed to identify reasons for gaps in pharmacy claims (true nonadherence or appropriate treatment holds). Outcomes included median PDC across sites, reasons for treatment gaps in patients with a PDC of <0.8, and the impact of adjusting PDC when accounting for appropriate therapy gaps. RESULTS: There were 29,994 prescriptions for 3,530 patients across 20 sites. The patient cohort was mostly female (75%), with a median age of 55 years (interquartile range [IQR], 42-63 years). The median PDC prior to chart review was 0.94 (IQR, 0.83-0.99). Upon review, 327 patients had no appropriate treatment gaps identified, 6 patients were excluded due to multiple unquantifiable appropriate gaps, and 420 patients had an adjustment in the PDC denominator due to appropriate treatment gaps (43 instances of days' supply adjusted based on discordant days' supply information between prescriptions and physician administration instructions, 11 instances of missing fills added, and 421 instances of clinically appropriate treatment gaps). The final median PDC after accounting for appropriate gaps in therapy was 0.95 (IQR, 0.87-0.99). CONCLUSION: This large, multisite retrospective cohort study was the first to demonstrate adherence rates across several HSSPs and provided novel insights into rates and reasons for appropriate gaps in therapy.
31961491 Health Care Utilization for Musculoskeletal Issues During the Prediagnosis Period in Psor 2021 May OBJECTIVE: Information about the prediagnosis period in psoriatic arthritis (PsA) is limited. The present study was undertaken to compare health care utilization related to musculoskeletal issues during a 5-year period prior to the diagnosis of PsA versus that of subjects with no prior inflammatory arthritis within a primary care setting. METHODS: We conducted a population-based, matched cohort study using electronic medical records and administrative data in Ontario, Canada. Age- and sex-matched cohorts of PsA patients and comparators from the same family physicians were assembled. Comparators were not allowed to have prior spondyloarthritis, ankylosing spondylitis, or rheumatoid arthritis billing code diagnoses. The study outcomes included health care utilization and costs related to nonspecific musculoskeletal issues during a 5-year period prior to the index date. RESULTS: We studied 462 PsA patients and 2,310 matched comparators. The odds ratio (OR) related to visiting a primary care physician for nonspecific musculoskeletal issues in patients with PsA was 2.14 (95% confidence interval 1.73-2.64) in the year immediately preceding the index date and was similarly elevated up to 5 years prior. The OR related to using other musculoskeletal-related health care services, including musculoskeletal specialists visits, joint injections, joint imaging, and emergency department visits, was higher in PsA as early as 5 years preceding the index date. Total and musculoskeletal-related health care costs prior to the index date were higher for patients with PsA versus comparators. CONCLUSION: A prodromal PsA phase characterized by nonspecific musculoskeletal symptoms may exist. Further study is needed to determine if this represents a window for earlier diagnosis of PsA.
33672699 Predictors of Progression and Mortality in Patients with Prevalent Rheumatoid Arthritis an 2021 Feb 20 OBJECTIVES: To describe a prospective cohort of patients with rheumatoid arthritis associated with interstitial lung disease (RA-ILD) and identify risk factors associated with disease progression and mortality in this cohort. PATIENTS AND METHODS: We performed a multicenter, prospective, observational study of patients with RA-ILD receiving disease-modifying antirheumatic drugs (DMARDs) between 2015 and 2020. The patients were assessed using high-resolution computed tomography and pulmonary function tests at baseline and at 60 months. The main endpoint was "Progression to ILD at the end of follow-up" in terms of the following outcomes: (1) improvement (i.e., improvement in forced vital capacity (FVC) ≥10% or diffusing capacity of the lungs for carbon monoxide (DLCO) ≥15% and absence of radiological progression); (2) nonprogression (stabilization or improvement in FVC ≤10% or diffusing capacity of the lungs for carbon monoxide (DLCO) <15% and absence of radiological progression); (3) progression (worsening of FVC >10% or DLCO >15% and radiological progression); or (4) death. We recorded demographic and clinical characteristics, lung function, and the incidence of adverse events. A Cox regression analysis was performed to identify factors associated with the worsening of ILD. RESULTS: After 60 months, lung disease had stabilized in 66 patients (56.9%), improved in 9 (7.8%), and worsened in 23 (19.8%). Eighteen patients (15.5%) died, with a mean survival of 71.8 (1.9) months after diagnosis of ILD. The Cox multivariate analysis revealed the independent predictors of worsening of RA-ILD to be usual interstitial pneumonia (hazard ratio (HR), 2.6 (95%CI, 1.0-6.7)), FVC <80% (HR, 3.8 (95%CI, 1.5-6.7)), anticitrullinated protein antibody titers (HR, 2.8 (95%CI, 1.1-6.8)), smoking (HR, 2.5 (95%CI, 1.1-6.2)), and treatment with abatacept, tocilizumab, or rituximab (HR, 0.4 (95%CI, 0.2-0.8)). During follow-up, 79 patients (68%) experienced an adverse event, mostly infection (61%). Infection was fatal in 10/18 patients (55.5%) during follow-up. CONCLUSIONS: Lung function is stable in most patients with RA-ILD receiving treatment with disease-modifying anti-rheumatic drugs (DMARDs), although one-third worsened or died. Identifying factors associated with worsening in RA-ILD is important for clinical management.
34588505 BTN2A2 protein negatively regulates T cells to ameliorate collagen-induced arthritis in mi 2021 Sep 29 Rheumatoid arthritis (RA) is an autoimmune disorder characterized by persistent inflammatory responses in target tissues and organs, resulting in the destruction of joints. Collagen type II (CII)-induced arthritis (CIA) is the most used animal model for human RA. Although BTN2A2 protein has been previously shown to inhibit T cell functions in vitro, its effect on autoimmune arthritis has not been reported. In this study, we investigate the ability of a recombinant BTN2A2-IgG2a Fc (BTN2A2-Ig) fusion protein to treat CIA. We show here that administration of BTN2A2-Ig attenuates established CIA, as compared with control Ig protein treatment. This is associated with reduced activation, proliferation and Th1/Th17 cytokine production of T cells in BTN2A2-Ig-treated CIA mice. BTN2A2-Ig also inhibits CII-specific T cell proliferation and Th1/Th17 cytokine production. Although the percentage of effector T cells is decreased in BTN2A2-Ig-treated CIA mice, the proportions of naive T cells and regulatory T cells is increased. Furthermore, BTN2A2-Ig reduces the percentage of proinflammatory M1 macrophages but increases the percentage of anti-inflammatory M2 macrophages in the CIA mice. Our results suggest that BTN2A2-Ig protein has the potential to be used in the treatment of collagen-induced arthritis models.
33788977 Alpha-1-antitrypsin reduces inflammation and exerts chondroprotection in arthritis. 2021 May While new treatments have been developed to control joint disease in rheumatoid arthritis, they are partially effective and do not promote structural repair of cartilage. Following an initial identification of α-1-Antitrypsin (AAT) during the resolution phase of acute inflammation, we report here the properties of this protein in the context of cartilage protection, joint inflammation, and associated pain behavior. Intra-articular and systemic administration of AAT reversed joint inflammation, nociception, and cartilage degradation in the KBxN serum and neutrophil elastase models of arthritis. Ex vivo analyses of arthritic joints revealed that AAT promoted transcription of col2a1, acan, and sox9 and downregulated mmp13 and adamts5 gene expression. In vitro studies using human chondrocytes revealed that SERPINA1 transfection and rAAT protein promoted chondrogenic differentiation through activation of PKA-dependent CREB signaling and inhibition of Wnt/β-catenin pathways. Thus, AAT is endowed with anti-inflammatory, analgesic, and chondroprotective properties that are partially inter-related. We propose that AAT could be developed for new therapeutic strategies to reduce arthritic pain and repair damaged cartilage.
33576004 Arthritis in systemic lupus erythematosus is characterized by local IL-17A and IL-6 expres 2021 Jul Arthritis is a common clinical feature of systemic lupus erythematosus (SLE) and is usually non-erosive, as opposed to rheumatoid arthritis (RA). While RA synovial pathology has been extensively studied, little is known about the pathophysiology of lupus arthritis. Here, we aimed to explore the cytokine and cellular compartments in synovial fluids of SLE patients with arthritic manifestations. Acellular synovial fluid and paired serum samples from SLE patients (n = 17) were analyzed with cytokine bead array for T helper-associated cytokines. From two SLE patients, synovial fluid mononuclear cells (SFMC) could also be captured and were analyzed by multiparameter flow cytometry to dissect T cell, B cell, monocyte and dendritic cell phenotypes. SLE-derived SFMC were further stimulated in vitro to measure their capacity for producing interferon (IFN)-γ and interleukin (IL)-17A. All patients fulfilled the ACR 1982 classification criteria for SLE. Clinical records were reviewed to exclude the presence of co-morbidities such as osteoarthritis or overlap with RA. IL-17A and IL-6 levels were high in SLE synovial fluid. A clear subset of the synovial CD4(+) T cells expressed CCR6(+) , a marker associated with T helper type 17 (Th17) cells. IL-17A-production was validated among CD4(+) CCR6(+) T cells following in-vitro stimulation. Furthermore, a strong IFN-γ production was observed in both CD4(+) and CD8(+) cells. Our study shows high IL-17A and IL-6 levels in synovial fluids of patients with lupus arthritis. The Th17 pathway has been implicated in several aspects of SLE disease pathogenesis and our data also point to Th17 involvement for lupus arthritis.
33651370 Prescribing Patterns and Impact of Factors Associated with Time to Initial Biologic Therap 2021 Mar OBJECTIVE: The aim of this study was to examine patterns of initial prescriptions, investigate time to initiation of biologic disease-modifying anti-rheumatic drugs (bDMARDs), and evaluate the impact of clinical and other baseline factors associated with the time to first bDMARD in treating children with newly diagnosed non-systemic juvenile idiopathic arthritis (JIA). METHODS: Using longitudinal patient-level data extracted from electronic medical records (EMR) in a large Midwestern pediatric hospital from 2009 to 2018, the initial prescriptions and prescribing patterns of bDMARDs, conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), non-steroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids within 3 months of JIA diagnosis were examined. Kaplan-Meier analyses were performed to assess time to initiation of bDMARDs. Cox proportional hazard models were used to identify factors associated with time to first bDMARD. RESULTS: Of 821 children, the proportion of patients with initial csDMARDs increased from 45.3% in 2009 to 60.3% in 2018. Around 57.5% of polyarthritis rheumatoid factor-positive (Poly RF+) patients and 43.2% of polyarthritis rheumatoid factor-negative (Poly RF-) patients received a bDMARD therapy within 3 months of diagnosis, 14.4% as monotherapy and 28.3% in combination with a csDMARD. Among patients who received combination therapy, combination of methotrexate with adalimumab increased from 16.7% in 2009 to 40% in 2018. The proportion of patients treated with adalimumab gradually increased and passed etanercept in 2016. The predictors of earlier initiation of biologic therapy were JIA category enthesitis-related arthritis (ERA) [hazard ratio (HR) vs persistent oligoarthritis 4.82; p < 0.0001], psoriatic arthritis (PsA) (HR 2.46; p = 0.0002), or Poly RF- (HR 2.43; p = 0.0002); the number of joints with limited range of motion (HR 1.02; p = 0.0222), and erythrocyte sedimentation rate (ESR, HR 1.01; p = 0.0033). CONCLUSIONS: There was a substantial increase in the proportion of patients receiving the combination of methotrexate and adalimumab among patients receiving combination therapy. Adalimumab overtook etanercept as the most frequently prescribed bDMARD. Multiple factors affect the time to biologic initiation, including the number of joints with limited range of motion, ESR, and JIA category.