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ID PMID Title PublicationDate abstract
35488289 Associated factors with poor treatment response to initial glucocorticoid therapy in patie 2022 Apr 29 BACKGROUND: High-dose glucocorticoids (GC) are first-line treatment for adult-onset Still's disease (AOSD); however, some of the patients remain refractory to initial GC therapy, or rapidly relapse. The aim of this study was to identify prognostic factors for poor treatment response to initial GC therapy for AOSD. METHODS: Data on newly diagnosed AOSD patients were extracted from our database (n=71, mean age 51.6 years). The primary outcome was a poor treatment outcome at 4 weeks, which was defined as failure to achieve remission or relapse after achieving remission within 4 weeks, followed by administration of two or more rounds of GC pulse therapy or of any other immunosuppressive drugs. RESULTS: The initial mean dose ± standard deviation of prednisolone was 0.82 ± 0.23 mg/kg/day, and 34 (47.3%) patients received GC pulse therapy at week 0. Twenty-nine of 71 patients exhibited a poor treatment outcome at 4 weeks (40.8%). The second round of GC pulse therapy or immunosuppressive drugs was added in 17 or 24 of the 29 patients, respectively. These patients had higher baseline white blood cell (WBC) counts, serum ferritin levels, systemic feature score based on clinical symptoms (modified systemic feature score, mSFS), more hemophagocytic syndrome (HPS) over the 4 weeks, and the higher severity score based on modified Pouchot score or severity index of the Japanese Ministry of Health, Labour and Welfare, than the remaining 42 patients. Multivariable logistic regression model identified baseline WBC count as a prognostic factor for poor outcome (odds ratio per 1000/μl increment: 1.12, 95% CI 1.04-1.29), while thrombocytopenia, hyperferritinemia, and mSFS at baseline did not achieve statistical significance. Receiver-operating characteristic curve analysis showed that the optimal cut-off for WBC count was 13,050/μl. The Kaplan-Meier method showed the cumulative rate of poor treatment outcome to be 60.0% in patients with WBC ≥13,050/μl and 23.5% in those with WBC <13,050/μl. CONCLUSIONS: A higher WBC count but not thrombocytopenia, hyperferritinemia, and mSFS at baseline was a significant prognostic factor for poor treatment outcome at week 4 in this retrospective cohort of AOSD patients. Our findings provide important information for determining the initial treatment strategy of newly-diagnosed AOSD.
35087513 High Dimensional Analyses of Circulating Immune Cells in Psoriatic Arthritis Detects Eleva 2021 Psoriatic arthritis (PsA) is a chronic inflammatory arthritis, affecting up to 40% of patients with psoriasis. Constitutive expression by CD4+ T cells of an active form of STAT3, a signal transducer and transcription factor, has been shown to induce many of the major features of PsA in an animal model. We used high dimensional mass cytometry (CyTOF) to probe ex-vivo levels of phosphorylated STAT3 (pSTAT3) in circulating immune cell subpopulations from PsA patients during active and inactive states. We evaluated the frequency of 16 immune cell populations and the levels of the activated forms of STAT3 (pSTAT3) and, for comparison, STAT1 (pSTAT1) and Src (pSrc) in whole blood fixed shortly after collection. In addition to PsA patients, we studied active rheumatoid arthritis (RA) patients. Increased levels of pSTAT3 were found in all the CD4+ T cell subsets analyzed, specifically, Th1, Th2, Th17, T follicular helper (Tfh) and T regulatory (Treg) as well as in CD14+CD16- (classical) monocytes from active PsA patients compared to inactive patients. After correcting for body mass index (BMI), smoking and conventional disease modifying antirheumatic drugs (c-DMARDs), levels of pSTAT3 levels remained increased in Th1 and Tfh CD4+ T cells, and in CD14+CD16- monocytes from active patients compared to inactive patients. No differences between the patient groups were observed for pSTAT1 or pSrc. No differences were found between the active PsA and active RA groups after correction for multiple testing. During active PsA, circulating Th1 and Tfh CD4+ T cells, and CD14+CD16- monocytes expressing high levels of pSTAT3 may play a role in PsA pathophysiology, perhaps by migration to inflamed sites.
35300214 Increased eEF2K Promotes Glycolysis and Aggressive Behaviors of Fibroblast-Like Synoviocyt 2022 OBJECTIVE: Aggressive phenotype and abnormal glycolytic metabolism of fibroblast-like synoviocytes (FLSs) are essential to joint inflammation and damage in rheumatoid arthritis (RA). Eukaryotic elongation factor-2 kinase (eEF2K) is a negative regulator of protein synthesis and has been shown to play an important role in regulating various cellular processes and promoting glycolysis in tumor cells. However, the role of eEF2K in regulating the pathogenic FLS behaviors is unknown. METHODS: A specific inhibitor of eEF2K, NH125, and siRNA were used to evaluate the role of eEF2K on RA FLSs in vitro. Collagen-induced arthritis (CIA) mice were used to evaluate the in vivo effect of eEF2K. Cell migration, invasion of RA FLSs were assessed by transwell or wound healing assays. Relative changes of cytokines were analyzed by quantitative real-time PCR, western blot and ELISA. RESULTS: Herein, we found an increased expression of eEF2K in synovial tissues and FLSs of RA patients. eEF2K knockdown by siRNA or treatment with NH125, an inhibitor of eEF2K, significantly reduced inflammation, migration/invasion, glucose uptake and lactate productions. eEF2K knockdown suppressed TNF-α-induced activation of NF-κB and AKT pathways in RA FLSs. Lactate reversed the inhibitory effect of eEF2K knockdown on inflammation and migration of RA FLSs. Moreover, lactate was also involved in eEF2K-mediated activation of NF-κB and AKT. NH125 treatment attenuated the severity of arthritis in collagen-induced arthritis mice. CONCLUSION: eEF2K inhibition suppressed glycolysis and aggressive behaviors of RA FLS, which indicated that targeting eEF2K may be a new strategy for the treatment of RA.
35359255 Daily physical activity measured by a wearable activity monitoring device in patients with 2022 Mar 31 INTRODUCTION: Activities of daily living in patients with rheumatoid arthritis (RA) have been evaluated by patient-reported outcomes. However, it has been difficult to measure activity intensity quantitively. Calories expended, exercise, and steps were measured quantitively by a wearable activity meter, and their associations with patients' background characteristics were examined. METHODS: Data from a prospective, observational study (CHIKARA study) were used. Eighty-five of 100 RA patients were entered and wore a wearable activity meter for 7 days. The daily calories expended and exercise for both walking and housework and steps were evaluated. Total daily calories expended and exercise was defined as the sum of walking and housework. The relationships of DAS28-ESR, mHAQ, body composition, muscle function, and general status were analyzed. RESULTS: The median age was 66.0 years, and the disease duration was 5.3 years. DAS28-ESR was 3.11, and mHAQ was 0.125. Total daily calories expended, exercise, and number of steps were 461.7 kcal, 3.97 METs h, and 4,788, respectively. MHAQ, walking speed, power, locomotive syndrome, and frailty were independently related to exercise. Total daily exercise and steps of the moderate and high disease activity group were significantly lower than those of the remission group. When the number of steps was < 3,333 and < 2,468, the odds ratios for locomotive syndrome and frailty increased 14.4-fold and 8.7-fold, respectively, using Fisher's exact test (P < 0.001). CONCLUSIONS: Daily physical activity and number of steps were significantly decreased in RA patients with moderate and high disease activity as measured by a wearable activity meter. Key Points • Total daily calories expended and exercise for both walking and housework and steps in patients with rheumatoid arthritis were 461.7 kcal, 3.97 METs h, and 4,788, respectively, using a wearable activity meter. • Daily physical activity, especially total daily exercise and number of steps, was significantly decreased in RA patients with moderate and high disease activity. • When total daily steps were < 3,333 and < 2,468, the odds ratios for locomotive syndrome and frailty increased 14.4-fold and 8.7-fold, respectively.
35499773 Sensory testing and topical capsaicin can characterize patients with rheumatoid arthritis. 2022 Apr 30 BACKGROUND AND OBJECTIVES: Our study aimed at examining the long-time inflammatory effects of rheumatoid arthritis (RA) as chronic immune-mediated disease on pain sensation and neuropathy development compared to healthy subjects (HS). METHODS: We used the quantitative sensory testing (QST) protocol of the German Research Network on Neuropathic Pain and Electroencephalography (EEG)-based contact heat evoked potentials (CHEPs) before and after topical capsaicin application. We recruited 16 RA patients in remission or low disease activity state (mean age: 59.38 years [± 10.18]) and 16 healthy subjects (mean age: 56.69 years [± 8.92]). RESULTS: The application of capsaicin cream on the thigh provoked a stronger effect in HS for both mechanical and heat pain thresholds (MPT and HPT, resp.), according to the area under the receiver operation characteristic (AUROC) (HS: HPT: 0.8965, MPT: 0.7402; RA: HPT: 0.7012, MPT: 0.6113). We observed contrary effects regarding changes in CHEPs (HS: g*max =  - 0.65; RA patients: g*max = 0.72). CONCLUSION: As the overall effect of topical capsaicin application was higher in HS for QST, we suggest the existence of a sensitization of TRPV1 channels in RA patients caused by long-time chronical inflammation, despite a lack of clinical signs of inflammation due to adequate treatment. The effect in CHEPs probably uncovers neuropathic symptoms. The effect of topical capsaicin on HPTs and CHEPs can act as a marker for the extent of sensitization and the development of neuropathic symptoms. Further studies are needed to prove if our proposed method can act as a marker for the success of anti-inflammatory treatment. Key Points • The effect of topical capsaicin may represent the extent of TRPV1 sensitization in rheumatoid arthritis. • The effect of topical capsaicin on the amplitude level of CHEPs can unmask neuropathic symptoms. • The effect of topical capsaicin on CHEPs and HPTs can show the long-term consequences and the treatment success of RA patients in remission.
35581954 Incidence and prevalence of seropositive rheumatoid arthritis among Korean women of childb 2022 May 19 BACKGROUND/AIMS: Women with rheumatoid arthritis (RA) are often diagnosed with the disease during their reproductive years; however, its incidence and prevalence among women of childbearing age have not been studied. The objective of this study was to estimate the incidence and prevalence of seropositive rheumatoid arthritis (SPRA) among Korean women of childbearing age. METHODS: Women aged 20 to 44 years with SPRA were identified from National Health Insurance Service-National Health Information Database (2009 to 2016). SPRA was defined by International Classification of Diseases, 10th revision code, M05. Incidence and prevalence were calculated per 100,000 person-years and stratified by year and age. RESULTS: The average incidence and prevalence of SPRA from 2011 to 2016 among women of childbearing age was 24.1/100,000 person-years (95% confidence interval [CI], 23.7 to 24.5) and 105.2/100,000 person-years (95% CI, 100.9 to 109.5), respectively. The incidence increased annually from 21.0/100,000 person-years (95% CI, 20.1 to 21.9) in 2009 to 28.4 person-years (95% CI, 27.3 to 29.5) in 2016. Similarly, the prevalence increased annually from 95.7/100,000 person-years (95% CI, 93.7 to 97.6) in 2009 to 111.0 person-years (95% CI, 108.9 to 113.2) in 2015, with a slight decrease in 2016 (110.4 person-years; 95% CI, 108.2 to 112.6). The incidence and prevalence of SPRA increased with advancing age. The peak age for both incidence and prevalence of SPRA among women of childbearing age was 40 to 44 years. CONCLUSIONS: The risk of SPRA is high in women during their childbearing years; this population bears a significant disease burden. This calls for special attention to this particular population group to reduce the risk and burden of this disease.
33563161 Appraisal of Anti-Arthritic and Anti-Inflammatory Potential of Folkloric Medicinal Plant P 2022 BACKGROUND & OBJECTIVE: Peganum harmala has been traditionally used to manage rheumatoid arthritis (RA) and other inflammatory conditions. However, its use against RA has not been scientifically evaluated. The current study was designed to assess the anti-arthritic and anti-inflammatory activities of the methanolic extract of P. harmala leaves by in vitro and in vivo methods. METHODS: The in vitro assays were carried out to determine the effect of plant extract on inhibition of egg albumin denaturation and human red blood cell membrane (HRBC) stabilization. Moreover, 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity was performed to determine the antioxidant potential. In vivo anti-arthritic activity was performed by determining the curative effect against Complete Freund's adjuvant (0.1 ml). The plant extract was administered to rats orally at 200, 400 and 600 mg/kg/day for 21 days. RESULTS: The values of IC50 of plant extract in protein denaturation, stabilization of HRBC and DPPH assays were 77.54 mg/ml, 23.90 mg/ml and 58.09 μg/ml, respectively. Moreover, the plant extract significantly attenuated the poly-arthritis and weight loss, anemia and paw edema. The plant extract restored the level of C-reactive protein, rheumatoid factor, alanine transaminase, aspartate transaminase and alkaline phosphatase in poly-arthritic rats. Moreover, the plant extract restored the immune organs' weight in treated rats. Treatment with P. harmala also significantly subdued the oxidative stress by reinstating superoxide dismutase, reduced glutathione, catalase and malondialdehyde in poly-arthritic rats. The plant extract notably restored the prostaglandin-E2 and tumor necrosis factor (TNF)-α in the serum of poly-arthritic rats. CONCLUSION: It was concluded that P. harmala extract had potential antioxidant, anti-inflammatory and antiarthritic activities, which primarily might be attributed to alkaloids, flavonoids and phenols.
35365828 Integrated Safety Analysis of Filgotinib Treatment for Rheumatoid Arthritis in Patients fr 2022 Apr 2 OBJECTIVE: Characterize safety of the Janus kinase-1 preferential inhibitor filgotinib in Japanese patients with moderately to severely active rheumatoid arthritis. METHODS: Data from three Phase 3 trials (NCT02889796, NCT02873936, NCT02886728) and a long-term extension (NCT03025308) through September 2019 were integrated; patients received ≥1 dose of filgotinib 200 (FIL200) or 100 mg (FIL100) daily, or placebo (PBO). We calculated exposure-adjusted incidence rates (EAIRs) per 100 patient-years filgotinib exposure (100PYE) for treatment-emergent adverse events (TEAEs) and adverse events of special interest. RESULTS: Among 3691 total patients and 6080.7 PYE, 229 Japanese patients received filgotinib for 311.4 PYE (median 1.5, maximum 2.5 years). During the 12-week PBO-controlled period, serious TEAEs and TEAEs leading to study drug disruption were comparable between filgotinib and PBO. Serious infection rates were 1.9%, 0%, and 2% for FIL200, FIL100, and PBO during the PBO-controlled period; long-term FIL200 and FIL100 EAIRs were 3.8 and 2.1/100PYE. No herpes zoster or major adverse cardiovascular events (MACE) occurred during the PBO-controlled period; long-term FIL200 and FIL100 EAIRs were 3.0 and 2.1/100PYE (herpes zoster) and 0.6 and 0/100PYE (MACE). CONCLUSION: Long-term filgotinib treatment (median 1.5, maximum 2.5 years exposure) was well tolerated at 100- and 200-mg doses in Japanese patients with rheumatoid arthritis.
35264827 Surgical Solution for Total Carpectomy due to Destructive Wrist Pan-Osteomyelitis Using a 2022 Jan Osteomyelitis of the hand is rare, even more so in the carpal bones. Patients with rheumatoid arthritis (RA) have a higher infection rate overall, and up to a 14-fold increase in the incidence of septic arthritis of the hand. The destruction of immunologic barriers, such as cartilage and joint capsules, as well as the use of immunosuppressive medications will have an impact on the higher incidence of articular infections and osteomyelitis in these patients. Infection in these cases is often overlooked because of the similarity of presentation to an acute event of RA. When osteomyelitis is present, rapid and aggressive treatment should be given. Surgical debridement, lavage, and excision of necrotic bone is the best choice, followed by cemented antibiotic impregnated spacer to resolve the acute scenario. Vascularized bone grafts (VBG) can then be used for a definitive solution, as these have great biologic properties that increase the possibility of a good outcome. We hereby present a report of a wrist arthrodesis, using a free medial femoral condyle VBG for the treatment of destructive osteomyelitis of the carpal bones in a female patient with RA.
35561482 LAT1-specific inhibitor ameliorates severe autoimmune arthritis in SKG mouse. 2022 May 11 L-type amino acid transporter 1 (LAT1, slc7a5) supplies large neutral amino acids to highly proliferative cells. LAT1 is an attractive therapeutic target for treating overactive T cell-mediated immune disorders due to its high expression in activated T cells, but not in resting T cells. Here, we demonstrate that LAT1 plays a crucial role in T helper (Th) 17-mediated autoimmune arthritis in SKG mice, an animal model of human rheumatoid arthritis (RA). Administration of JPH203, a LAT1-specific inhibitor, suppressed mannan-induced joint swelling, synoviocyte proliferation and inflammatory cell infiltration in SKG mice. A diminished metabolic reprogramming, including a decrease in oxidative phosphorylation that regulates Hif-1α expression and subsequent control of glycolysis enzymes, was involved in the downregulation of Th17 differentiation by LAT1 inhibition. Moreover, publicly released database analysis revealed facilitated expression of LAT1 in T cells with cytotoxic features in patients with RA. Our results demonstrate the essential contribution of LAT1 to the development of RA, proposing a potential therapeutic approach targeting amino acid transporters for treating hypersensitive immune diseases.
35031905 Na-AIP-1 secreted by human hookworms suppresses collagen-induced arthritis. 2022 Apr Proteins from helminths have been posed as new immunomodulatory agents with exciting potential in the treatment of immune-mediated diseases including rheumatoid arthritis (RA). In this study we assess the effects of a helminthic excretory/secretory (ES) protein Na-AIP-1 as monotherapy and in combination with methotrexate (MTX) in the well-described collagen-induced arthritis (CIA) model of RA. CIA was induced in DBA/1 J mice which were treated after the onset of arthritis with Na-AIP-1 monotherapy, MTX or Na-AIP-1 + MTX. The clinical scores for weight, arthritis and paw width were recorded along with joint histology as outcome measures. For the clinical parameters of weight, paw score and paw width, none of the Na-AIP-1 monotherapy, MTX therapy or Na-AIP-1 + MTX combination therapy groups displayed any significant difference when compared to the arthritis control. However, a significant reduction in histological score was identified after both monotherapy (Na-AIP-1: 0.83 ± 0.24 vs Arthritis control: 5.58 ± 1.49, p = 0.0277) and combination therapy (Na-AIP-1 + MTX: 0.55 ± 0.28 vs Arthritis control: 5.58 ± 1.49, p = 0.0233) when compared to arthritis control. Furthermore, Na-AIP-1 as both monotherapy (Na-AIP-1: 0.83 ± 0.24 vs MTX: 5.73 ± 1.82 p = 0.0261) and combination therapy (Na-AIP-1 + MTX: 0.55 ± 0.28 vs MTX: 5.73 ± 1.82, p = 0.0221) also significantly reduced histological score when compared to MTX monotherapy. Na-AIP-1 significantly reduced joint pathology in CIA. The hookworm protein Na-AIP-1 seems to be effective in the treatment of RA as monotherapy and when dosed together with MTX, constituting a potential new candidate for drug development. Research should focus on elucidating the mechanism of Na-AIP-1 action as a means to identify novel targets for therapeutics and to further our current understanding of immunobiology in RA.
35605832 Evaluated serum perfluoroalkyl acids and their relationships with the incidence of rheumat 2022 May 20 Perfluoroalkyl acids (PFAAs) are widely present in human blood, and have many toxic effects on humans. However, effects of PFAA exposure on the risk of rheumatic immune diseases are limited. In the present study, occurrence of 7 PFAAs, including perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoate (PFNA), perfluorodecanoate (PFDA), perfluoroundecanoate (PFUnA), perfluorododecanoate (PFDoA), and perfluorotrdecanoate (PFTrA), were measured in serum samples from 156 healthy people (controls) and 156 rheumatoid arthritis (RA) cases living in Hangzhou, China. We also investigated the relationships among cumulative PFAA levels in serum, some immune markers, and the incidence of RA. The results showed that PFOA (6.1 and 11.8 ng/mL) had the highest mean serum concentrations, followed by PFOS (3.2 and 3.4 ng/mL) and PFDA (0.86 and 2.6 ng/mL), in both controls and RA cases. Cumulative exposure to PFOA in the study population were positively correlated with the levels of rheumatoid factors (r(s) = 0.69, p < 0.01) and anti-cyclic citrullinated peptide antibody (r(s) = 0.56, p < 0.05). Moreover, significant associations of PFOA concentrations with odds ratios (OR) of RA (OR = 1.998, confidence interval (CI): 1.623, 2.361, p = 0.01) were found by adjusting for various covariates. The crude and adjusted OR for RA was respective 1.385 (95% CI: 1.270, 1.510, p = 0.04) and 1.381 (95% CI: 0.972, 1.658, p = 0.06) for a unit increase in serum PFOS levels, but the adjusted results were not significant. Overall, this case-control study found that human serum PFOA concentrations were positively correlated with RF and ACPA levels.
35465588 Role of Shear Wave Elastography of Synovium to Differentiate Rheumatoid and Tubercular Art 2022 Jan BACKGROUND: Synovitis is the underlying pathology in various arthritis, and sometimes, it is difficult to differentiate various arthritis clinically or even by imaging. The purpose of our study was to use shear wave elastography (SWE) to evaluate rheumatoid arthritis (RA) and tubercular (TB) arthritis and to differentiate them using synovial stiffness. METHODS: The prospective study was performed on Supersonic Imagine Aixplorer Ultrasound (USG) machine using a linear array probe SL10-2 (2-10 MHz). A total of 29 participants, 15 of RA (ACR/EULAR criteria) and 14 of proven TB arthritis were included. Region of interest of 1 mm was applied on the hypertrophied synovium and quantitative SWE data in form of elasticity (kPa) and velocity (m/s) were measured. Discrete categorical data were presented as n (%). Mean values were recorded along with standard deviation and the range of values. To find a maximal cutoff value of elasticity and velocity - receiver operating characteristic curve were plotted. RESULTS: The mean elasticity and velocity values were 54.81 ± 10.6 kPa and 4.2 m/s ± 0.42 for RA and 37 ± 10 kPa and 3.4 ± 0.47 m/s for TB group. Significant difference (P < 0.001) was seen in elastic modulus values between rheumatoid and TB group with cutoff of 43.6 kPa to differentiate the two groups (sensitivity - 86.7% and specificity - 80%). Similar significant (P < 0.001) results were seen with velocity values, with cutoff of 3.76 m/s (sensitivity - 86.7% and specificity - 80%). CONCLUSION: SWE shows the potential to be a useful adjunct to gray scale and color Doppler USG in differentiating various arthritis on the basis of elastic properties of the synovium. Elastic modulus and velocity are useful SWE quantitative parameters for synovial evaluation and can differentiate RA and TB arthritis.
35629398 The Role of Inflammasomes in Osteoarthritis and Secondary Joint Degeneration Diseases. 2022 May 13 Osteoarthritis is age-related and the most common form of arthritis. The main characteristics of the disease are progressive loss of cartilage and secondary synovial inflammation, which finally result in pain, joint stiffness, and functional disability. Similarly, joint degeneration is characteristic of systemic inflammatory diseases such as rheumatoid arthritis and gout, with the associated secondary type of osteoarthritis. Studies suggest that inflammation importantly contributes to the progression of the disease. Particularly, cytokines TNFα and IL-1β drive catabolic signaling in affected joints. IL-1β is a product of inflammasome activation. Inflammasomes are inflammatory multiprotein complexes that propagate inflammation in various autoimmune and autoinflammatory conditions through cell death and the release of inflammatory cytokines and damage-associated molecule patterns. In this article, we review genetic, marker, and animal studies that establish inflammasomes as important drivers of secondary arthritis and discuss the current evidence for inflammasome involvement in primary osteoarthritis. The NLRP3 inflammasome has a significant role in the development of secondary osteoarthritis, and several studies have provided evidence of its role in the development of primary osteoarthritis, while other inflammasomes cannot be excluded. Inflammasome-targeted therapeutic options might thus provide a promising strategy to tackle these debilitating diseases.
35613869 Therapeutic strategy for rheumatoid arthritis by induction of myeloid-derived suppressor c 2022 May 24 Combination treatment using fingolimod (FTY720), an immunomodulator, and a pathogenic antigen prevents the progression of glucose-6-phosphate isomerase (GPI)(325-339)-induced arthritis. In this study, we focused on myeloid-derived suppressor cells (MDSCs; CD11b(+)Gr-1(+) cells) and investigated the effects of the combination treatment on these cells. DBA/1J mice with GPI(325-339)-induced arthritis were treated using FTY720 and/or GPI(325-339) for five days. The expanded CD11b(+)Gr-1(+) cell population and its inhibitory potential were examined. The percentage of CD369(+)CD11b(+)Gr-1(+) cells effectively increased in the combination-treated mice. The inhibitory potential of CD369(+)CD11b(+)Gr-1(+) cells was higher than that of cells not expressing CD369. Among bone marrow cells, the expression of CD369 in CD11b(+)Gr-1(+) cells increased following stimulation with granulocyte-macrophage colony-stimulating factor, and the expression of CD11c increased accordingly. The increased CD11c expression indicated a decrease in the potential to suppress T cell proliferation based on the results of the suppression assay. The percentage of CD11c(-)CD369(+) cells in CD11b(+)Gr-1(+) cells that were induced by the combination treatment also increased, and these cells tended to have a higher capacity to inhibit T cell proliferation. In conclusion, the combination treatment using FTY720 and the pathogenic antigen effectively induces MDSC, which demonstrates a high potential for suppressing T cell proliferation in the lymph nodes, thereby establishing an immune-tolerant state.
35562091 Metabolomics and molecular docking-directed antiarthritic study of the ethyl acetate extra 2022 Aug 10 ETHNOPHARMACOLOGICAL RELEVANCE: Celastrus orbiculatus Thunb., an important folk medicine, has long been used for the treatment of rheumatoid arthritis and its ethyl acetate extract (COE) has been reported to possess anticancer, antiinflammation and antiarthritic effects. However, the therapeutic effect and mechanism of COE treatment in rheumatoid arthritis has been rarely studied especially from the perspective of metabolomics. AIM OF STUDY: To reveal the therapeutic effects of COE on adjuvant-induced arthritis (AIA) rats through histopathological analysis, non-targeted metabolomics, and molecular docking study. MATERIALS AND METHODS: Forty-three Wistar rats were randomly divided into normal group, AIA model group, methotrexate group, and COE groups (80 mg/kg, 160 mg/kg and 320 mg/kg of ethyl acetate extract). Paw swelling and arthritis score were monitored through the experiment. Serum levels of tumor necrosis factor α (TNF-α) and nitric oxide were determined and histopathological evaluation was performed. Furthermore, Ultra-high performance liquid chromatography-linear trap quadrupole-Orbitrap-based metabolomics was employed to characterize metabolic changes of AIA rats after COE treatment and molecular docking was performed to predict the potential phytochemicals of COE against TNF-α. RESULTS: COE at three dosages could significantly relieve paw swelling and reduce arthritis scores of AIA rat. Histopathological analysis revealed remarkable decrease in synovial inflammation and bone erosion after COE treatment, especially at middle and high dosage. Additionally, COE down-regulated serum levels of TNF-α and nitric oxide. Serum metabolomics showed that 22 potential biomarkers for the COE treatment of AIA rats were identified, which were closely related to fatty acid metabolism, glycerophospholipid catabolism, and tryptophan metabolism. The molecular docking models predicted that olean-type triterpenes in COE may contribute most to therapeutic effects of rheumatoid arthritis through targeting TNF-α. CONCLUSIONS: COE could significantly relieve the arthritic symptoms in AIA rats and the ultra-high performance liquid chromatography-mass spectrometry based metabolomics proved to be an efficient method to characterize subtle metabolic changes of AIA rats after COE treatment.
34870800 Clinical Management of Herpes Zoster in Patients With Rheumatoid Arthritis or Psoriatic Ar 2022 Feb INTRODUCTION: Risk of herpes zoster (HZ) is increased with Janus kinase inhibitor use. We evaluated clinical study data relating to HZ management in patients with rheumatoid arthritis (RA) or psoriatic arthritis (PsA) receiving tofacitinib. METHODS: This post hoc analysis included data from 21 RA and 3 PsA clinical studies; data were pooled for tofacitinib doses. Outcomes of HZ events (serious and non-serious) and tofacitinib treatment changes were evaluated in response to first and second HZ events. Median time to resolution was stratified by dermatomal involvement, history of HZ prior to tofacitinib, changes to tofacitinib treatment, anti-viral and corticosteroid use, and tofacitinib dose. RESULTS: Seven hundred eighty-three (11.1%, N = 7061) patients with RA experienced ≥ 1 HZ event, 63 (8.0%) of whom had ≥ 2 HZ events. In patients with PsA, 36 (4.6%, N = 783) experienced ≥ 1 HZ event, 1 (2.8%) of whom had ≥ 2 HZ events. For most HZ events, tofacitinib treatment was unchanged or temporarily discontinued. The majority of patients received anti-viral treatment, most within 3 days of onset. Post-herpetic neuralgia developed in 6.9% and 3.2% of patients with RA with first and second events, respectively, and in 2.8% of patients with PsA with a first event. Most first and second events resolved (RA: 97.6% and 96.8%, respectively; PsA: 94.4% and 100%, respectively). Median time to resolution was 22.0 days for first and 15.0 days for second events for RA and 20.5 days for first and 11.0 days for second events (n = 1) for PsA. Time to resolution of first events for RA and PsA was generally numerically shorter for patients with single dermatomal HZ, history of HZ, or anti-viral use versus those without. CONCLUSION: Among patients receiving tofacitinib, recurrent events were more common in patients with RA versus PsA; HZ duration was shorter for repeat events. TRIAL REGISTRATION: NCT01262118, NCT01484561, NCT00147498, NCT00413660, NCT00550446, NCT00603512, NCT00687193, NCT01164579, NCT00976599, NCT01059864, NCT01359150, NCT02147587, NCT00960440, NCT00847613, NCT00814307, NCT00856544, NCT00853385, NCT01039688, NCT02187055, NCT00413699, NCT00661661, NCT01877668, NCT01882439, NCT01976364.
35016827 Surgically treated reactive arthritis of the ankle after COVID-19 infection: A case report 2022 Apr A 37-year-old man developed right ankle pain and swelling six days after being diagnosed with coronavirus disease (COVID-19). Despite conservative treatment, his ankle symptoms persisted. Magnetic resonance imaging and computed tomography showed synovial hypertrophy and bone erosion in the ankle. Following arthroscopic synovectomy, performed 69 days after the COVID-19 diagnosis, the pain improved significantly. The clinical course was consistent with that of reactive arthritis following severe acute respiratory syndrome coronavirus 2 infection. The pathological findings resembled rheumatoid nodules. The bone erosion may have originated from the inflammatory pathway, which resembles the mechanism of rheumatoid arthritis.
35154716 Ankle arthrodesis using a retrograde intramedullary rod with fins for highly destructive j 2022 Feb Herein, we present two cases of older adult patients with highly destructive changes in ankle joints (Larsen grade IV) who underwent retrograde intramedullary ankle nail fixation with fins. In both patients, bony union was achieved, and full weight-bearing was attained at 3 months after surgery.
35096114 Jin-Wu-Jian-Gu Formulation Attenuates Rheumatoid Arthritis by Inhibiting the IL33-ST2 Sign 2022 The present research attempted to investigate the molecular mechanism of Jin-Wu-Jian-Gu Formulation (JWJGF) in inhibiting rheumatoid arthritis (RA) in a pharmacological approach for analysis and experimental validation. First, the potential targets and pathways of JWJGF for RA were predicted by network pharmacology. Second, the effect of JWJGF on RA was observed by hematoxylin-eosin (HE) staining and enzyme-linked immunosorbent assay (ELISA). Further, we observed the effects of JWJGF on the IL33-ST2 signaling pathway by Western blot and quantitative real-time PCR (qPCR) experiments, and finally, we studied the effects of Liquiritigenin on rheumatoid arthritis synovial fibroblast (RASF) cells and the IL33-ST2 signaling pathway. Network pharmacology results showed that the key component of JWJGF was Liquiritigenin and the core target of JWJGF was IL-33. The results of HE and ELISA showed that JWJGF could alleviate RA. Western blot and qPCR findings indicated that JWJGF could inhibit the IL33-ST2 signaling pathway. Furthermore, JWJGF could inhibit the proliferation of RASF cells and the IL33-ST2 signaling pathway. In conclusion, this study revealed that JWJGF attenuated RA by inhibiting the IL33-ST2 signaling pathway.