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ID PMID Title PublicationDate abstract
31480869 An overview of carbonic anhydrases and membrane channels of synoviocytes in inflamed joint 2019 Dec The highly aggressive fibroblast-like synoviocytes (FLSs) are inflammatory mediators involved in synovial joint destruction. Membrane channels and transporters are essential components of the cell migration apparatus and are involved in various cellular functions. Although evidence is emerging that cell migration is a physiological/pathological process, the mechanism of highly dynamic synoviocytes linked to the membrane channels and carbonic anhydrases (CAs) in inflamed joints is only partially understood. In this review, topics covered will give a brief overview of CAs and the membrane channels of synoviocytes. We have also systematically focused on the role of FLS channels and transporters under various conditions, including rheumatoid arthritis (RA), to understand the pathophysiology of the migration of synoviocytes as inflammatory mediators in joints.
30648758 Melatonin attenuates TNF-α and IL-1β expression in synovial fibroblasts and diminishes c 2019 Apr The hormone melatonin has many properties, including antioxidant, anti-inflammatory, and immunomodulatory effects. Melatonin has been demonstrated to be beneficial in several inflammatory autoimmune diseases, but its effects in rheumatoid arthritis (RA) remain controversial. We sought to determine how melatonin regulates inflammation in RA. We found that melatonin dose-dependently inhibits tumor necrosis factor-α (TNF-α) and interleukin (IL)-1β expression through the PI3K/AKT, ERK, and NF-κB signaling pathways. We also identified that melatonin inhibits TNF-α and IL-1β production by upregulating miR-3150a-3p expression. Synovial tissue specimens from RA patients and culture of human rheumatoid fibroblast-like synoviocytes confirmed that the MT1 receptor is needed for the anti-inflammatory activities of melatonin. Importantly, melatonin also significantly reduced paw swelling, cartilage degradation, and bone erosion in the collagen-induced arthritis mouse model. Our results indicate that melatonin ameliorates RA by inhibiting TNF-α and IL-1β production through downregulation of the PI3K/AKT, ERK, NF-κB signaling pathways, as well as miR-3150a-3p overexpression. The role of melatonin as an adjuvant treatment in patients with RA deserves further clinical studies.
30093238 Acceptance rate and sociological factors involved in the switch from originator to biosimi 2019 Apr OBJECTIVE: To study acceptance rate and factors influencing acceptance of the switch from originator etanercept (Enbrel©) to biosimilar etanercept (SB4, Bénépali©) in patients with rheumatic disease. METHODS: Patients with a well-controlled rheumatic disease consulting in our rheumatology department were offered the switch for SB4. After oral and written information concerning biosimilar, free choice to accept the switch was left to the patients. The main outcome was primary switch acceptance rate defined by switch acceptance during the initial consult. Real switch adherence, socio-cultural factors and beliefs influencing switch acceptance rate were retrieved during a telephonic interview at distance from the consultation. RESULTS: Fifty-two patients were eligible for the switch: 32 (62%) with spondyloarthritis and 20 (38%) with rheumatoid arthritis. The primary acceptance rate was 92% (48/52). Patients refusing the switch were more likely to report a bad opinion on generic drugs (100% vs 11%, p < 0.001). Other patient characteristics were roughly identical except for a statistical trend in the refusal group toward older age (61.4vs 50.7years, p = 0.08) and longer disease duration (26vs 12.1years, p = 0.05). Despite initial acceptance, two patients did not begin SB4 after receiving negative information by their regular pharmacist. Real SB4 switch rate was 85% (44/52) and 86% (38/44) of patients reported a good experience of the switch. CONCLUSIONS: Acceptance rate of the switch from originator to biosimilar etanercept is high. Patient information, physician and pharmacist knowledge on biosimilars should be taken into account in order to improve their diffusion.
31694746 Validation of two frailty questionnaires in older patients with rheumatoid arthritis: a cr 2020 May OBJECTIVES: Several questionnaires exist to assess frailty, a geriatric syndrome. None of these has been validated in older patients with rheumatoid arthritis (RA). Our objective was to assess aspects of validity of two frailty questionnaires: Groningen Frailty Indicator (GFI) and Geriatric 8 (G8) among RA patients. METHODS: In a cross-sectional study among patients ≥65 years information was collected on socio-demographics, disease characteristics including comorbidities and physical function and on frailty using the GFI and G8. Content validity was assessed by linking items of the GFI and G8 to the International Classification of Functioning, Disability and Health (ICF). Classic psychometric methods were used to test hypotheses on construct validity and interpretability. RESULTS: Eighty patients (74.6 years (SD 5.9); 66% female) participated. The GFI has more items on social and mental functions; the G8 more on functions of the digestive system (e.g. nutritional status). As hypothesised, correlations (r) with physical function (RGFI=0.54; RG8=0.56) and disease activity (RGFI=0.24; RG8=0.36) were moderate to weak. However, correlations with age (RGFI=0.20; RG8=0.11) or comorbidities (RGFI=0.30; RG8=0.16) were lower than expected. Instrument-specific thresholds classified 43 (54%) of participants as frail on the GFI and 44 (55%) on the G8; 33 (41%) were frail on both instruments. CONCLUSIONS: The GFI and G8 differ in content with more emphasis on nutritional status for the G8. Both instruments are insensitive to age and comorbidities. Before deciding on their usefulness in RA, their predictive validity for mortality and resource utilisation independent of disease activity and physical function should be further evaluated.
31049403 cIAP1/2 inhibition synergizes with TNF inhibition in autoimmunity by down-regulating IL-17 2019 May IL-17 and TNF-α are major effector cytokines in chronic inflammation. TNF-α inhibitors have revolutionized the treatment of rheumatoid arthritis (RA), although not all patients respond, and most relapse after treatment withdrawal. This may be due to a paradoxical exacerbation of T(H)17 responses by TNF-α inhibition. We examined the therapeutic potential of targeting cellular inhibitors of apoptosis 1 and 2 (cIAP1/2) in inflammation by its influence on human T(H) subsets and mice with collagen-induced arthritis. Inhibition of cIAP1/2 abrogated CD4(+) IL-17A differentiation and IL-17 production. This was a direct effect on T cells, mediated by reducing NFATc1 expression. In mice, cIAP1/2 inhibition, when combined with etanercept, abrogated disease activity, which was associated with an increase in T(regs) and was sustained after therapy retraction. We reveal an unexpected role for cIAP1/2 in regulating the balance between T(H)17 and T(regs) and suggest that combined therapeutic inhibition could induce long-term remission in inflammatory diseases.
31154006 A population pharmacokinetic study to accelerate early phase clinical development for a no 2019 Aug 1 PURPOSE: To accelerate early phase clinical development of a novel drug, teriflunomide sodium, to treat systemic lupus erythematosus (SLE) based on the data of leflunomide. METHODS: Based on a pharmacokinetic (PK) study assessing the relative bioavailability of teriflunomide sodium compared to leflunomide, a population pharmacokinetic (Pop PK) analysis was firstly conducted using non-linear mixed effect model. Covariates were thoughtfully screened after Pop PK model evaluation and qualification using various diagnostic plots, visual predicted check (VPC) and bootstrap method. In order to predict teriflunomide PK profiles for multiple dosing of teriflunomide sodium in SLE patients, a model integrating enterohepatic circulation (EHC) mechanism was utilized to simulate the teriflunomide PK profile after multiple dosing of 20 mg/day leflunomide, and compare it to the teriflunomide PK profile in a 20 mg/day leflunomide multiple dose study in rheumatoid arthritis patients. Validated EHC PK model was applied to optimize dose regimen for teriflunomide sodium in SLE patients. RESULTS: A population one-compartment model with pulsed EHC characteristic was developed to capture teriflunomide PK profiles after administration of leflunomide and teriflunomide sodium. Body weight and male sex were found to significantly increase apparent volume of central compartment. ABCG2 34G>A polymorphism was found to significantly change apparent clearance and absorption rate. The Pop PK model was evaluated and validated. After this model was confirmed to capture EHC characteristics of teriflunomide in both healthy subjects and patients with rheumatoid arthritis after single and multiple dosing leflunomide, it was applied to suggest dose regimen of teriflunomide sodium in phase II study. CONCLUSIONS: The pulsed EHC Pop PK model characterized the teriflunomide PK processes well in both healthy subjects and patients. Body weight, sex, and ABCG2 34G>A genotype were identified to significantly affect PK characteristics. The developed EHC Pop PK model exhibited the ability to predict PK profiles of teriflunomide in patients after long-term dosing and could be utilized to support phase II trial design.
31644891 Heat-killed probiotic regulates the body's regulatory immunity to attenuate subsequent exp 2019 Dec Administration of inactivated probiotics has been proved to enhance host immunity. Herein, we aim to explore their potential in modulating systemic autoimmune disorders. The bovine type II collagen (CII)-induced arthritis (CIA) and CII antibody-induced arthritis (CAIA) mice models were used in this study. Heat-killed Lactobacillus reuteri (h-L. reuteri) was administered before or after the induction of CIA. The results indicated that the severity of CIA was alleviated and the prevalence of CIA was decreased in the mice pre-treated with h-L. reuteri. Using enzyme-linked immunosorbent assays, we found that decreased serum CII-specific IgG antibody IL-6 and CXCL1 but the increased level of IL-10 was found in h-L. reuteri-treated cohort. Moreover, h-L. reuteri treatment decreased the severity and incidence of arthritis in the CAIA model which was associated with a early decrease of IL-6. Systematic supplement of exogenous IL-6 reversed h-L. reuteri-induced CIA suppression. For regulatory immune responses, the frequency of Tregs and CD4+IL-10+ cells was increased in the draining lymph of joint of h-L. reuteri-treated mice after second immunization. Parallelly, we found that if CIA was induced, CD103+ dendritic cells in mesenteric lymph nodes and α4β7+ Tregs in the spleen were increased in h-L. reuteri-treated mice, suggesting h-L. reuteri might affect the peripheral migration of Tregs to modulating CIA. Finally, the mice with progressive CIA were treated with h-L. reuteri after the second immunization. No alleviation of CIA severity, as well as an increase of splenic α4β7+ Tregs, was observed in these mice. This study indicates that pre-administration of h-L. reuteri can alleviate the CIA in mice and may serve as a promising strategy for autoimmune disease prevention.
31309334 Apparent diffusion coefficient as an indicator of spinal cord compression due to anterior 2019 Oct PURPOSE: The aim of this retrospective study was to evaluate the apparent diffusion coefficient (ADC) as a potential parameter of spinal cord damage in cervical spine instability at the atlanto-axial level in rheumatoid arthritis (RA) patients. METHODS: One hundred and six RA patients were included in the study. MRI examinations were performed with 1.5T scanner. The ADC was measured at six locations in the cervical spinal cord at the height of the first six cervical vertebrae (from C-1 to C-6). The ADC values were assessed in 2 groups: with and without anterior atlanto-axial subluxation (AAS) diagnosed on plain radiographs. Correlations between ADC values and radiographic measurements and RA activity indicators were evaluated. RESULTS: The ADC values at C1 level (ADC(1)) was higher in the group with anterior AAS than in the group without AAS (p < 0.001). Statistically significant moderate positive correlation between ADC(1) and anterior atlanto-axial diameter interval AADI (rho = 0.58; p < 0.008) was found as well as statistically significant weak negative correlation between ADC(1) and posterior atlanto-axial diameter interval PADI (rho =  - 0.34; p < 0.008). CONCLUSIONS: The conducted study demonstrates the applicability of the ADC maps in the identification of spinal cord compression due to anterior AAS in RA patients. The results encourage the practical use of the ADC as an additional parameter in the qualification for surgical treatment. These slides can be retrieved under Electronic Supplementary Material.
30659893 Potential therapeutic effect of curcumin loaded hyalurosomes against inflammatory and oxid 2019 Mar In the present work curcumin loaded hyalurosomes were proposed as innovative systems for the treatment of rheumatoid arthritis. Vesicles were prepared using a one-step and environmentally friendly method. Aiming at finding the most suitable formulation in terms of size, surface charge and stability on storage, an extensive pre-formulation study was performed using different type and amount of phospholipids. Curcumin loaded vesicles prepared with 180 mg/ml of Phospholipon 90G (P90G) and immobilized with sodium hyaluronate (2 mg/ml) were selected because of their small size (189 nm), homogeneous dispersion (PI 0.24), negative charge (-35 mV), suitable ability to incorporate high amount of curcumin (E% ∼88%) and great stability on storage. The in vitro study using fibroblast-like synovial cells cultured in synovial fluid, demonstrated the ability of these vesicles to downregulate the production of anti-apoptotic proteins IAP1 and IAP2 and stimulate the production of IL-10, while the production of IL-6 and IL-15 and reactive oxygen species was reduced, confirming their suitability in counteracting pathogenesis of rheumatoid arthritis.
30789095 Activated neutrophil carbamylates albumin via the release of myeloperoxidase and reactive 2020 Mar Objective: An anti-carbamylated albumin antibody was detected in rheumatoid arthritis (RA) patients, and its presence was associated with serum myeloperoxidase (MPO) levels, as we reported previously. Since MPO is a key enzyme for carbamylation and is released by neutrophil extracellular traps (NETs), we aimed to demonstrate that NETosis induces carbamylation.Methods: Human neutrophils were isolated from a healthy donor, pre-treated with or without diphenyleneiodonium (DPI, an inhibitor for the generation of reactive oxygen species (ROS)), Cl-amidine (a peptidylarginine deiminase inhibitor), 4-aminobenzoic acid hydrazide (4-ABAH, an MPO inhibitor), or GW311616A (a neutrophil elastase (NE) inhibitor), and incubated for 8 h with or without phorbol 12-myristate 13-acetate (PMA). Proteins in the medium were collected and the carbamylation of albumin was evaluated by Western blotting.Results: The carbamylation of albumin was detected in the culture medium of activated neutrophils. NETosis was observed under the stimulation by PMA. DPI and 4-ABAH inhibited the carbamylation of albumin and NETosis. GW311616A inhibited NETosis, but not carbamylation. Neither carbamylation nor NETosis was inhibited by Cl-amidine.Conclusion: Activated neutrophils may carbamylate ambient albumin, and this is dependent on ROS and MPO, but does not require NETosis.
29172405 Risk of malignancy in patients with rheumatoid arthritis after anti-tumor necrosis factor 2019 May BACKGROUND/AIMS: Inhibition of tumor necrosis factor (TNF) is an effective treatment for rheumatoid arthritis (RA), but safety concerns about malignancy remain. The aim of this study was to evaluate cancer risk in RA patients treated with TNF inhibitors (TNFi), based on Korean Nationwide Health Insurance claims data. METHODS: Patients with seropositive RA were selected from the health insurance database containing all citizens' medical information, based on both RA diagnosis codes and medications. Between 2010 and 2014, RA patients treated with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) and TNFi were enrolled and followed up. We compared the cancer incidence between patients treated with TNFi and csDMARDs using incidence rate ratios (IRRs) after adjustment for age, gender, and observational periods. RESULTS: Of 45,423 selected patients with seropositive RA, 2,337 were treated with TNFi and 43,086 were treated with csDMARDs. The TNFi group was younger and was followed-up for a longer duration. During the observational period, 1,732 and 49 cases of cancer were detected in patients treated with csDMARDs and TNFi, respectively. Old age and male sex were associated with cancer occurrence. Adjusted IRRs for all cancers and common cancers demonstrated that cancer incidence did not differ significantly between the TNFi group and csDMARDs group (IRR = 0.913 for all cancers, p = 0.546). CONCLUSION: This study revealed that cancer incidence was similar in RA patients treated with TNFi and csDMARDs. Anti-TNF therapy may be a safe therapeutic option for RA treatment, in terms of malignancy.
32039051 Oral Microbiota Perturbations Are Linked to High Risk for Rheumatoid Arthritis. 2019 Oral microbial dysbiosis is known to increase susceptibility of an individual to develop rheumatoid arthritis (RA). Individuals at-risk of RA may undergo different phases of disease progression. In this study, we aim to investigate whether and whereby the oral microbiome communities alter prior to symptoms of RA. Seventy-nine saliva samples were collected from 29 high-risk individuals, who were positive for anti-citrullinated protein antibodies (ACPA) and have no clinical arthritis, 27 RA patients and 23 healthy controls (HCs). The salivary microbiome was examined using 16S ribosomal RNA gene sequencing. Alpha and beta diversity analysis and the linear discriminant analysis were applied to examine the bacterial diversity, community structure and discriminatory taxa between three groups, respectively. The correlation between salivary bacteria and autoantibodies were analyzed. In the "pre-clinical" stages, salivary microbial diversity was significantly reduced comparing to RA patients and HCs. In contrast to HCs, like RA patients, individuals at high-risk for RA showed a reduction in the abundance of genus Defluviitaleaceae_UCG-011 and the species Neisseria oralis, but an expansion of Prevotella_6. Unexpectedly, the relative abundance of Porphyromonas gingivalis, reported as opportunistic pathogens for RA development, was significantly decreased in high-risk individuals. Additionally, we identified four genera in the saliva from high-risk individuals positively correlated with serum ACPA titers, and the other two genera inversely displayed. In summary, we observed a characteristic compositional change of salivary microbes in individuals at high-risk for RA, suggesting that oral microbiota dysbiosis occurs in the "pre-clinical" stage of RA and are correlated with systemic autoimmune features.
31866621 Gamma heavy chain disease (γ-HCD) as iatrogenic immunodeficiency- associated lymphoprolif 2019 Gamma heavy chain disease (γ-HCD) is a rare B-cell neoplasm that produces a truncated immunoglobulin γ-heavy chain lacking the light chain. The clinical features of γ-HCD are heterogeneous, resembling different types of B-cell lymphomas. Although rheumatoid arthritis (RA) is one of the common underlying diseases of γ-HCD, the therapeutic modality for RA has changed greatly in recent years; therefore, γ-HCD as iatrogenic immunodeficiency-associated lymphoproliferative disorder (LPD) should be taken into consideration. Here, we report such a γ-HCD case. A 69-year-old female was admitted because of fever, multiple lymph node swelling in the abdominal cavity, and peritoneal effusion. She had been treated using methotrexate for RA for 14 years, and using infliximab and adalimumab for Crohn's disease for one year. The serum concentration of IgG was 3,525 mg/dL, which was revealed to be monoclonal IgG lacking the light chain by rocket immunoselection assay. CD19(+)/CD20(-)/smκ(-)/smλ(-) large abnormal lymphocytes were observed in the peritoneal fluid, which were demonstrated to be clonal B-cells by PCR examination. Discontinuation of methotrexate did not improve her condition and she died of pneumonia. Many abnormal lymphocytes positive for IgG and EBER but negative for the light chain were found on immunohistological examination of necropsy specimens from the spleen and bone marrow.
30814379 [Control of inflammatory bone destruction by targeting the Wnt signaling pathway.]. 2019 Bone erosions develop early in the course of rheumatoid arthritis(RA)and are predictive of a worse prognosis. They deteriorate gradually and cause joint damage, resulting in impaired functional capacity and disability. Lately, a considerable number of studies have increased our understanding of the pathogenic mechanisms participating in the development of bone erosions in RA. Osteoclasts are responsible cells and multiple factors have been identified to stimulate their differentiation and function. RANKL(receptor activator of NF-κB ligand)and other cytokines have been known for a long time to enhance osteoclastogenesis, but the role of other pathways has also been revealed recently. Besides to excessive ostaoclastogenesis, impair osteoblast differentiation and function also plays part in bone erosion formation in RA. Inflamed synovial membrane products increased levels of cytokines and antagonists of the canonical Wnt signaling pathway, which inhibit osteoblast differentiation and function. It seems that downregulation of this pathway leads to impaired osteoblast differentiation and activity and consequently, to reduced capacity of bone erosion to repair. Preclinical studies show that these findings could have implications in RA treatment, although more studies are required in this direction.
31699130 Does the nitrogen single-breath washout test contribute to detecting pulmonary involvement 2019 Nov 7 OBJECTIVE: There has been growing interest in studying small airway disease through measures of ventilation distribution, thanks to the resurgence of the nitrogen single-breath washout (N(2)SBW) test. Therefore, this study evaluated the contribution of the N(2)SBW test to the detection of pulmonary involvement in patients with rheumatoid arthritis (RA). RESULTS: Twenty-one patients with RA underwent clinical evaluation, pulmonary function tests (PFTs), including the N2(S)BW test, and computed tomography (CT). The main tomographic findings were air trapping and bronchiectasis (57.1% and 23.8% of cases, respectively). According to the phase III slope of the N(2)SBW (phase III slope), 11 and 10 patients had values < 120% predicted and > 120% predicted, respectively. Five patients with limited involvement on CT had a phase III slope > 120%. The residual volume/total lung capacity ratio was significantly different between patients with phase III slopes < 120% and > 120% (P = 0.024). Additionally, rheumatoid factor positivity was higher in patients with a phase III slope > 120% (P = 0.021). In patients with RA and airway disease on CT, the N(2)SBW test detects inhomogeneity in the ventilation distribution in approximately half of the cases, even in those with normal conventional PFT results.
30695794 Effect of IL-6 Receptor Blockade on Proprotein Convertase Subtilisin/Kexin Type-9 and Chol 2019 Mar The aim of the work was to examine whether abnormalities in the lipid profile that tocilizumab (TCZ), an anti-IL-6 receptor Ab, exerts in rheumatoid arthritis (RA) patients is related to changes in either proprotein convertase subtilisin/kexin-9 (PCSK9) serum concentrations or in serum cholesterol efflux capacity (CEC). TOCRIVAR is a one-year prospective clinical trial that analyzes the influence of TCZ on cardiovascular risk factors. Twenty-seven RA patients receiving TCZ (8 mg/kg IV/q4w) were assessed at baseline and weeks 12, 24, and 52. Disease activity indexes, adiposity composition, physical activity, serum CEC, PCSK9, and lipoproteins serum concentrations were assessed at every visit. Basal high-sensitivity C-reactive protein (hs-CRP) and disease activity were markedly reduced throughout one-year TCZ treatment. While initially total cholesterol and LDL cholesterol increased their plasma concentration, decreasing to basal afterwards, lipoprotein(a) was significantly lower than basal in all visits of the study. CEC increased after 24 week of treatment proportionally to hs-CRP reduction, and remained significantly higher after week 52 [median % change 32 (3-141), p=0.021]. Interestingly, variations in LDL cholesterol basal concentration along the one year of TCZ treatment correlated directly with changes of PCSK9 serum concentration (r=0.37, p=0.003). Basal abdominal adiposity, BMI, and physical activity remained stable during the study. Long-term TCZ-treated RA patients show an increment in CEC inversely proportional to hs-CRP reduction and changes in LDL cholesterol that might be explained, at least in part, by variations in PCSK9 plasma concentration. Overall, TCZ treatment produces a favorable qualitative net effect in terms of atherogenic implication in RA patients.
30976834 Successful arthroscopic treatment of refractory and complicated popliteal cyst associated 2019 Dec Although popliteal cysts are most frequently identified in patients with osteoarthritis (OA), they may occur in patients with rheumatoid arthritis (RA), in which serious complicated cases such as cyst rupture can be developed. The objective of this study was to report four patients with RA (six knees) in combination with OA with a brief review of literature of previous similar published cases. This is a retrospective review of case records of patients with refractory and/or complicated popliteal cysts, who have successfully treated with arthroscopic intervention. We suggest that arthroscopic interventions such as radical debridement, synovectomy, biomechanical valve excision, and/or cystectomy should be considered in patients with refractory and complicated popliteal cysts associated with RA or RA in combination with OA.
31586092 Imaging Rheumatoid Arthritis in Mice Using Combined Near Infrared and (19)F Magnetic Reson 2019 Oct 4 Rheumatoid arthritis (RA) is an autoimmune disease that causes pain and tissue destruction in people worldwide. An accurate diagnosis is paramount in order to develop an effective treatment plan. This study demonstrates that combining near infrared (NIR) imaging and (19)F MRI with the injection of labelled nanoparticles provides high diagnostic specificity for RA. The nanoparticles were made from poly(ethylene glycol)-block-poly(lactic-co-glycolic acid) (NP) or PLGA-PEG-Folate (Folate-NP), loaded with perfluorooctyl bromide (PFOB) and indocyanine green (ICG) and evaluated in vitro and in a collagen-induced arthritic (CIA) mouse model. The different particles had a similar size and a spherical shape according to dynamic light scattering (DLS) and transmission electron microscopy (TEM). Based on flow cytometry and (19)F MRI analysis, Folate-NP yielded a higher uptake than NP in activated macrophages in vitro. The potential RA-targeting ability of the particles was studied in CIA mice using NIR and (19)F MRI analysis. Both NP and Folate-NP accumulated in the RA tissues, where they were visible in NIR and (19)F MRI for up to 24 hours. The presence of folate as a targeting ligand significantly improved the NIR signal from inflamed tissue at the early time point (2 hours), but not at later time points. Overall, these results suggest that our nanoparticles can be applied for combined NIR and (19)F MRI imaging for improved RA diagnosis.
30521345 Route to Rheumatoid Arthritis by Macrophage-Derived Microvesicle-Coated Nanoparticles. 2019 Jan 9 The targeted delivery of therapeutics to sites of rheumatoid arthritis (RA) has been a long-standing challenge. Inspired by the intrinsic inflammation-targeting capacity of macrophages, a macrophage-derived microvesicle (MMV)-coated nanoparticle (MNP) was developed for targeting RA. The MMV was efficiently produced through a novel method. Cytochalasin B (CB) was applied to relax the interaction between the cytoskeleton and membrane of macrophages, thus stimulating MMV secretion. The proteomic profile of the MMV was analyzed by iTRAQ (isobaric tags for relative and absolute quantitation). The MMV membrane proteins were similar to those of macrophages, indicating that the MMV could exhibit bioactivity similar to that of RA-targeting macrophages. A poly(lactic- co-glycolic acid) (PLGA) nanoparticle was subsequently coated with MMV, and the inflammation-mediated targeting capacity of the MNP was evaluated both in vitro and in vivo. The in vitro binding of MNP to inflamed HUVECs was significantly stronger than that of the red blood cell membrane-coated nanoparticle (RNP). Compared with bare NP and RNP, MNP showed a significantly enhanced targeting effect in vivo in a collagen-induced arthritis (CIA) mouse model. The targeting mechanism was subsequently revealed according to the proteomic analysis, indicating that Mac-1 and CD44 contributed to the outstanding targeting effect of the MNP. A model drug, tacrolimus, was encapsulated in MNP (T-RNP) and significantly suppressed the progression of RA in mice. The present study demonstrates MMV as a promising and rich material, with which to mimic macrophages, and demonstrates that MNP is an efficient biomimetic vehicle for RA targeting and treatment.
31203225 Rituximab Therapy for Systemic Rheumatoid Vasculitis: Indications, Outcomes, and Adverse E 2020 Apr OBJECTIVE: To characterize the indication, outcomes, and adverse effects of rituximab (RTX) treatment in a large single-center cohort of patients with systemic rheumatoid vasculitis (RV). METHODS: We retrospectively reviewed the medical charts of 17 patients treated with RTX for systemic RV from 2000 to 2017. Clinical characteristics, outcomes, and adverse effects were analyzed. RESULTS: At RV diagnosis, mean age was 59 years, 59% were female, 94% were white, and 82% had positive rheumatoid factor. At the time of initiating RTX, median Birmingham Vasculitis Activity Score for rheumatoid arthritis was 4.0 (interquartile range 2.0-7.5). RV presented in the skin in 8 patients (47%), as mononeuritis multiplex in 2 (12%), inflammatory ocular disease in 2 (12%), and affected multiple organ systems in 5 (29%). RTX was used for induction therapy in 8 patients (47%), relapsing RV in 4 (24%), second-line therapy in 2 (12%), and salvage therapy or in combination with another agent in 3 (18%). At 3 months, 2 (13%) of 15 patients with available followup information achieved complete remission (CR), and 10 (67%) achieved partial response (PR). At 6 months, 6 patients (40%) achieved CR, 8 (53%) achieved PR, and one had no response. At 12 months, 8 of 13 patients with available records (62%) had CR and 5 patients (38%) had PR. CONCLUSION: Systemic RV is difficult to treat effectively. CR of RV was achieved in 62% and PR in 38% of patients within 12 months of RTX use. Further evidence is needed to inform treatment for patients with RV.