Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
29848137 Nurse-like cells in rheumatoid arthritis: Formation of survival niches cooperating between 2019 May Nurse-like cells (NLCs) established from bone marrow and synovial tissue of rheumatoid arthritis (RA) patients were found to promote maturation and differentiation of B lineage cells as well as T cells. In co-culture of RA-NLCs and B cells, tight physical interactions (pseudoemperipolesis) developed, which resulted in activation of both cell types. RA-NLCs also supported myeloid cell maturation, promoting their differentiation into tartrate-resistant acid phosphatase-positive mononuclear cells, which are precursor cells of osteoclasts. In RA synovial tissue, the characteristic dendritic-shaped cells (the DCs) were electron microscopically found to form direct physical interactions with adjacent plasma cells (PCs) suspecting to be pseudoemperipolesis. The numbers of PCs accumulating in various areas tended to correlate with the numbers of the DCs, which appeared to have RA-NLC functions forming survival niches for PCs. Immunohistochemical staining analysis indicated that CD14+ cells including the DCs formed survival niches for CD138+ PCs by RA-NLC functions. Quantitative dual immunofluorescence staining studies of these areas indicated that the majority of CD14+ cells were of myeloid lineage. These survival niches promoted by RA-NLCs appear to play important roles in supporting immunological functions in RA bone marrow and synovial tissues.
31370159 Mesenchymal Stem Cells in Homeostasis and Systemic Diseases: Hypothesis, Evidences, and Th 2019 Jul 31 Mesenchymal stem cells (MSCs) are present in all organs and tissues, playing a well-known function in tissue regeneration. However, there is also evidence indicating a broader role of MSCs in tissue homeostasis. In vivo studies have shown MSC paracrine mechanisms displaying proliferative, immunoregulatory, anti-oxidative, or angiogenic activity. In addition, recent studies also demonstrate that depletion and/or dysfunction of MSCs are associated with several systemic diseases, such as lupus, diabetes, psoriasis, and rheumatoid arthritis, as well as with aging and frailty syndrome. In this review, we hypothesize about the role of MSCs as keepers of tissue homeostasis as well as modulators in a variety of inflammatory and degenerative systemic diseases. This scenario opens the possibility for the use of secretome-derived products from MSCs as new therapeutic agents in order to restore tissue homeostasis, instead of the classical paradigm "one disease, one drug".
31483954 MiR-22 restrains proliferation of rheumatoid arthritis by targeting IL6R and may be concer 2020 Jan It has demonstrated that miR-22 overexpression can suppress the inflammation process of rheumatoid arthritis (RA) in synoviocytes. But, the underlying mechanism of miR-22 expression in regulating RA is still not well illustrated. In this study, we investigated the functional role and underlying mechanism of miR-22 in regulating RA. Human RA fibroblast-like synoviocyte (FLS) cell line MH7A cells was transfected by miR-22 mimic and its control. CCK8 was utilized to detect cell proliferation. Cell apoptosis was analyzed by flow cytometry. MH7A cells stimulating with interleukin-1β (IL-1β) were transfected with miR-22 mimic. Quantitative real time polymerase chain reaction (qRT-PCR) and western blot assays were utilized to detect mRNA and protein expression. miR-22 targets were predicted and validated by Targetscan and luciferase reporter assay. We revealed that miR-22 showed downregulated expression in MH7A after stimulation with IL-1β. Additionally, miR-22 overexpression suppressed the proliferation and facilitated apoptosis in MH7A cells. IL6R was a target of miR-22. Besides, miR-22 overexpression inhibited the expression of IL6R and also suppressed inflammatory pathway NF-κB. These results indicated that miR-22 overexpression could restrain the activity of inflammation cells in RA by targeting IL6R and might be concerned with the inhibition of NF-κB pathway.
30890451 Flexible two-layer dissolving and safing microneedle transdermal of neurotoxin: A biocomfo 2019 May 30 This study is directed towards the gentle transdermal delivery of Neurotoxin (NT) and study of the treatment of Rheumatoid Arthritis (RA) in rats by NT loaded dissolving Microneedles (DMNs-NT). The DMNs-NT fabrication involved a two-step centrifugation method. The quadrangular pyramid shape needles had great mechanical strength. The upper part of the needle contained 15.4 ± 0.5 μg of drug per patch. Blank DMNs showed favorable biocompatibility and low toxicity on the chondrocyte cells. Both NT and DMNs-NT displayed anti-inflammatory capabilities ex-vitro. The results of ex-vitro evaluation of DMNs the skin penetration depth of DMNs-NT rats was higher than 70 μm and the cumulative penetration of NT in DMNs could reach 95.8% in 4 h, whereas, the NT solution could barely penetrate the skin, thereby proving the favorable facilitation of NT transdermal delivery. The needle structure dissolved completely after 10 min in vivo and the channel on the Stratum Corneum (SC) was closed after 6 h. There was no significant adverse reaction on the skin after 15 days of administration. The pharmacodynamic study showed that DMNs-NT significantly reduced the toe swelling of RA rats and reduced the levels of TNF-α and IL-1β in serum to alleviate the injury of the ankle joints. DMNs-NT held favorable stability in 3 months. All these results established that DMNs-NT could penetrate the skin of rats in a biocompatible manner, and have a strong therapeutic effect on rat RA by transdermal delivery.
31174592 Safety of abatacept compared with other biologic and conventional synthetic disease-modify 2019 Jun 7 BACKGROUND: To assess the risks of malignancies, infections and autoimmune diseases in patients with rheumatoid arthritis (RA) treated with abatacept compared with other biologic (b) disease-modifying antirheumatic drugs (DMARDs) or conventional synthetic (cs)DMARDs, in a US-wide observational RA cohort METHODS: Data were reviewed from patients (≥ 18 years) with RA who were registered with FORWARD, the National Databank for Rheumatic Diseases, and who initiated abatacept, other bDMARDs or csDMARDs between 2005 and 2015. Patients who switched treatment during the study could be allocated to more than one group. The incidence rates (IRs) by treatment were calculated for malignancies, hospitalized infections and autoimmune diseases identified by six monthly questionnaires and medical records. The hazard ratios (HRs) (95% confidence intervals [CIs]) for all outcomes with abatacept compared with other bDMARDs or csDMARDs were determined using marginal structural models adjusted for clinical confounders. RESULTS: In the study sample, 1496 initiated abatacept, 3490 initiated another bDMARD and 1520 initiated a csDMARD. The risk of malignancies with abatacept was not statistically significant versus other bDMARDs (HR [95% CI)] 1.89 [0.93, 3.84]) or versus csDMARDs (HR [95% CI] 0.93 [0.20, 4.27]). Patients receiving abatacept versus other bDMARDs were at a lower risk of hospitalized infections (HR [95% CI] 0.37 [0.18, 0.75]); the risk versus csDMARDs was lower with wide CIs (HR [95% CI] 0.31 [0.09, 1.05]). The relative risks for psoriasis were similar between treatment groups (HR [95% CI] 1.46 [0.76, 2.81] and HR [95% CI] 2.05 [0.59, 7.16] for abatacept versus other bDMARDs and versus csDMARDS, respectively). The IR (95% CI) of severe infusion/injection reactions was lower with abatacept compared with other bDMARDs (1.57 [1.11, 2.17] vs 2.31 [1.87, 2.82] per 100 patient-years, respectively). CONCLUSIONS: In this analysis, abatacept was well tolerated and did not result in an overall increased risk of malignancies, infections or autoimmune diseases compared with other bDMARDs or csDMARDs.
30073800 Brief Report: Influence of Disease Activity in Rheumatoid Arthritis on Radiographic Progre 2019 Jan OBJECTIVE: Distal interphalangeal (DIP) joints are commonly considered to be unaffected by rheumatoid arthritis (RA). Despite synovitis and bone marrow edema being associated with radiographic progression in hand osteoarthritis (OA) and hand RA, radiographic courses differ substantially. This study was undertaken to analyze incidence and progression of radiographically evident DIP joint OA in RA patients, in relation to RA activity and patient characteristics. METHODS: In sequential radiographs of 1,988 RA patients in the Swiss Clinical Quality Management in Rheumatic Diseases registry, we evaluated and scored 15,904 DIP joints. Scoring was based on the presence of central erosions and subchondral sclerosis and on the severity of osteophytes and joint space narrowing, according to the modified Kellgren/Lawrence (K/L) grade. The presence of DIP joint OA was defined as ≥1 joint with a K/L grade of ≥2, and progression was defined as an increase in a summed K/L grade. Adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. RESULTS: The median follow-up time was 4.5 years (interquartile range 3.1-7.0), and the mean ± SD age was 56.1 ± 11.1 years. DIP joint OA was present in 60% of patients at baseline. Higher mean age (OR 1.09 [95% CI 1.08-1.10]), female sex (OR 1.37 [95% CI 1.08-1.74]), and higher mean body mass index (OR 1.03 [95% CI 1.00-1.06]) were associated with the presence of DIP joint OA, but neither the presence of anti-citrullinated protein antibodies (ACPAs) (OR 0.72 [95% CI 0.50-1.03]) nor the presence of rheumatoid factor (OR 1.01 [95% CI 0.74-1.38]) were associated with it. Disease Activity Score using the erythrocyte sedimentation rate and metacarpophalangeal (MCP) joint erosions were not associated with DIP joint OA progression. RA disease duration had no relevant effect size associated with DIP joint OA progression (OR 0.97 [95% CI 0.96-0.99]). CONCLUSION: Known risk factors for DIP joint OA were replicated in patients with RA. The observation that RA activity, the presence of ACPA, and MCP joint erosions were not associated with the prevalence or progression of DIP joint OA indicates that there are distinct roles of inflammation in the pathogenesis of RA and DIP joint OA.
30221490 Patient Perspectives on Intravenous Biologics for Rheumatologic Disease. 2019 Sep OBJECTIVE: Two surveys were conducted with patients with rheumatologic diseases to evaluate perceptions of different routes of administration (intravenous [IV] or subcutaneous [SC]) for biologic therapy. METHODS: In Survey I, patient preferences toward biologic treatment were evaluated at a rheumatology practice in Buffalo, New York. In Survey II, Canadian patients enrolled in the BioAdvance patient support program and scheduled to receive IV biologic therapy were asked about their opinions of IV treatment. RESULTS: In Survey I, 243 rheumatology patients participated. Median patient age was 60 years, 76% were female, and 44% were naive to treatment with biologic agents. Among biologic-naive patients, the majority (56%) were open to either SC or IV treatment; biologic-naive women were more likely than men to express a preference for the route of administration. In Survey II, 1,598 patients from the BioAdvance program (including 306 rheumatology patients) completed the full survey. Among the rheumatology patients, the median age was 49 years, 58% were female, and 61% had not previously taken biologics before enrolling in the BioAdvance program. The median rating of IV favorability (on a 10-point scale, with higher numbers indicating increased favorability) recalled by rheumatology patients was 5 prior to their first program infusion, which increased to 9 after multiple treatment infusions. CONCLUSION: These survey results indicate that patients with rheumatoid arthritis are generally open to IV treatment and express high satisfaction with IV therapy. Additional patient and provider education may improve shared decision-making regarding biologic therapy administration options.
31722720 Bone marrow mesenchymal stem cells in rheumatoid arthritis, spondyloarthritis, and ankylos 2019 Nov 13 BACKGROUND: Bone marrow mesenchymal stem cells (BM-MSCs) can dampen inflammation in animal models of inflammatory rheumatisms and human osteoarthritis. They are expected to be a solution for numerous human conditions. However, in rheumatoid arthritis (RA) and spondyloarthritis (SpA), subsets of subchondral BM-MSCs might conversely fuel synovitis and enthesitis. MAIN TEXT: Abnormal behaviour of BM-MSCs and/or their progeny has been found in RA and SpA. BM-MSCs also contribute to the ossifying processes observed in ankylosing spondylitis. Some synovial fibroblastic stem cells probably derive from BM-MSCs, but some stem cells can also migrate through the bare zone area of joints, not covered by cartilage, into the synovium. BM-MSCs can also migrate in the synovium over tendons. Sub-populations of bone marrow stem cells also invade the soft tissue side of enthesis via small holes in the bone cortex. The present review aims (1) to make a focus on these two aspects and (2) to put forward the hypothesis that lasting epigenetic changes of some BM-MSCs, induced by transient infections of the bone marrow close to the synovium and/or entheses (i.e. trained immunity of BM-MSCs and/or their progeny), contribute to the pathogenesis of inflammatory rheumatisms. Such hypothesis would fit with (1) the uneven distribution and/or flares of arthritis and enthesitis observed at the individual level in RA and SpA (reminiscent of what is observed following reactive arthritis and/or in Whipple's disease); (2) the subchondral bone marrow oedema and erosions occurring in many RA patients, in the bare zone area; and (3) the frequent relapses of RA and SpA despite bone marrow transplantation, whereas most BM-MSCs resist graft preconditioning. CONCLUSION: Some BM-MSCs might be more the problem than the solution in inflammatory rheumatisms. Subchondral bone marrow BM-MSCs and their progeny trafficking through the bare zone area of joints or holes in the bone cortex of entheses should be thoroughly studied in RA and SpA respectively. This may be done first in animal models. Mini-arthroscopy of joints could also be used in humans to specifically sample tissues close to the bare zone and/or enthesis areas.
30909697 IL-1 family cytokines in chronic inflammatory disorders. 2019 Winter IL-1 family represent a group of structurally related cytokines with prevailing pro-inflammatory (IL-1α, IL-1β, IL-18, IL-33, IL-36α, IL-36β a IL-37γ) or anti-inflammatory (IL-1Ra, IL-36Ra, IL-38, IL-37) effects. They are involved not only in defense mechanisms and physiological modulation of homeostatic processes, but also in the imunopathogenesis of many diseases including rheumatoid arthritis, inflammatory bowel disease, autoimmune and auto-inflammatory diseases. Recently, advances in biologic therapy enabled blocking of IL-1α, IL-1β, IL-18, and IL-33 with new monoclonal antibodies, soluble receptors, or recombinant binding proteins.
30767867 IL-35 prevent bone loss through promotion of bone formation and angiogenesis in rheumatoid 2019 Sep OBJECTIVES: Angiogenesis in bone and osteogenesis appear to be closely linked, suggesting the existence of molecular crosstalk between pro-angiogenic molecules and osteoblasts. The pro-angiogenic molecules vascular endothelial growth factor (VEGF) with its receptors Flt-1, Flk-1 and fibroblast growth factor (FGF)-2 play a crucial role in born formation, an early and critical event in the pathogenesis of rheumatoid arthritis (RA). Interleukin (IL)-35 is demonstrated to be an anti-inflammatory cytokine in RA. However, the mechanisms involved are not fully understood. This study aims to investigate whether IL-35 has an impact on angiogenesis in osteoblasts and its related signalling pathway in RA. METHODS: The effects of IL-35 on osteoblasts proliferation, apoptosis and pro-angiogenic molecules mRNA and protein were examined using osteoblast-like MC3T3E1 cells in vitro. The effects of IL-35 on proliferation and apoptosis were examined using cell counting kit-8 (CCK-8) assay and flow cytometry, respectively. Pro-angiogenic molecules expression were assessed by real time PCR and ELISA, respectively. The signalling pathway between IL-35, bone formation, angiogenesis and signalling pathway was also investigated. RESULTS: IL-35 promoted osteoblasts proliferation and inhibited apoptosis in a dose-dependent manner in vitro. IL-35 increased basal and TNF-α induced pro-angiogenic molecules expression by osteoblasts. Blocking the Th17/IL-17 signalling pathway with plumbagin inhibited the pro-angiogenic effects of IL-35 in osteoblasts. CONCLUSIONS: These results suggested that IL-35 promotes bone formation and angiogenesis by fostering osteoblasts proliferation, inhibiting apoptosis and upregulating pro-angiogenic molecules through Th17/IL-17 related-signalling pathway. Our findings extend the current understanding of mechanisms modulating bone formation and angiogenesis in RA.
30941747 The links of hepcidin and erythropoietin in the interplay of inflammation and iron deficie 2019 Jul Anaemia affects quality of life and radiographic outcome in rheumatoid arthritis (RA). In a cross-sectional study with 779 patients, we assessed the prognostic potential of the major haematopoietic regulators, hepcidin and erythropoietin, comparing their serum concentrations with respect to different anaemia types, inflammatory activity, anti-cytokine-specific treatment effects and iron deficiency (ID) indices. The results showed that clinical disease activity was more closely associated with haemoglobin levels than with anti-tumour necrosis factor-alpha or interleukin 6 receptor effects. In ID, hepcidin was suppressed, independently of inflammation. Erythropoietin levels were inappropriately low in relation to the degree of anaemia, but, in contrast to low haemoglobin, not directly associated with joint damage progression. Hepcidin and erythropoietin levels are intimately connected with inflammation and ID. Interventional studies on these important targets are already in progress.
31614480 Andrographolide Ameliorates Rheumatoid Arthritis by Regulating the Apoptosis-NETosis Balan 2019 Oct 11 Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by symmetric polyarthritis with swelling and pain at synovial joints. In RA patients, delayed neutrophil apoptosis amplifies the inflammatory response and massively released neutrophil extracellular traps (NETs) induce tissue damage and provide self-antigens. Andrographolide (AD) is the major active labdane diterpenoid derived from Andrographis paniculata, which has multiple pharmacological effects, including hepatoprotection, anti-angiogenesis, anti-thrombosis, and anti-inflammation. In the present study, we investigated the effect of AD on an adjuvant-induced arthritis (AA) murine model of RA and found that AD alleviated murine arthritis by reducing neutrophil infiltration and NETosis in the ankle joints and relieved the systematic inflammation. In vitro experiments showed that AD accelerated the apoptosis of lipopolysaccharide-activated neutrophils and inhibited autophagy-dependent extracellular traps formation of neutrophils. These findings suggest that AD has considerable potential for RA therapy.
31795133 Apoptosis Induction of Fibroblast-Like Synoviocytes Is an Important Molecular-Mechanism fo 2019 Nov 28 Rheumatoid arthritis (RA) is a known chronic autoimmune disease can cause joint deformity and even loss of joint function. Fibroblast-like synoviocytes (FLS), one of the main cell types in synovial tissues of RA patients, are key effector cells in the development of RA and are considered as promising therapeutic targets for treating RA. Herbal medicines are precious resources for finding novel agents for treating various diseases including RA. It is reported that induction of apoptosis in FLS is an important mechanism for the herbal medicines to treat RA. Consequently, this paper reviewed the current available references on pro-apoptotic effects of herbal medicines on FLS and summarized the related possible signal pathways. Taken together, the main related signal pathways are concluded as death receptors mediated apoptotic pathway, mitochondrial dependent apoptotic pathway, NF-κB mediated apoptotic pathways, mitogen-activated protein kinase (MAPK) mediated apoptotic pathway, endoplasmic reticulum stress (ERS) mediated apoptotic pathway, PI3K-Akt mediated apoptotic pathway, and other reported pathways such as janus kinase/signal transducers and activators of transcription (JAK-STAT) signal pathway. Understanding the apoptosis induction pathways in FLS of these herbal medicines will not only help clear molecular mechanisms of herbal medicines for treating RA but also be beneficial for finding novel candidate therapeutic drugs from natural herbal medicines. Thus, we expect the present review will highlight the importance of herbal medicines and its components for treating RA via induction of apoptosis in FLS, and provide some directions for the future development of these mentioned herbal medicines as anti-RA drugs in clinical.
30569216 Inhibition of periarticular bone loss is associated with clinical remission and ACR70-Resp 2019 Apr The aim of this study, based on a post hoc analysis of the data set used in the RAPID 1 trial, focuses on the associations between metacarpal bone mineral density, as estimated by digital X-ray radiogrammetry (DXR), and clinical remission as well as ACR70-Response in rheumatoid arthritis (RA) patients treated with certolizumab pegol (CZP). The trial evaluates a total of 345 RA patients treated with methotrexate versus CZP 200 mg versus CZP 400 mg. All patients underwent X-rays of the hand at baseline and week 52 as well as computerized calculations of bone mineral density (BMD) by DXR. Clinical remission was defined as DAS28 < 2.6. ACR70-Response was also evaluated. The radiological assessment of disease progression was estimated using the modified total Sharp Score. The mean difference for DAS28 was observed for patients treated with CZP 400 mg (median: - 3.53, minimum: - 6.77; maximum: + 0.48) and CZP 200 mg (median: - 3.13, minimum: - 6.37; maximum: - 0.52) compared to the methotrexate group (median - 2.41, minimum: - 4.76; maximum: + 0.31). The DXR-BMD showed a minor bone loss for the treatment groups undergoing therapy with CZP 200 mg (median: - 0.009 g/cm(2), minimum: - 0.059 g/cm(2); maximum: + 0.095 g/cm(2)) and CZP 400 mg (median: - 0.008 g/cm(2), minimum: - 0.064 g/cm(2); maximum: + 0.080 g/cm(2)). The methotrexate group presented an advanced periarticular metacarpal bone loss as measured by DXR-BMD (median: - 0.024 g/cm(2), minimum: - 0.102 g/cm(2); maximum: + 0.057 g/cm(2)). In the case of clinical remission and ACR70-Response, no significant change of the DXR-BMD was observed for both CZP groups. The study highlights that patients treated with CZP show a less accentuated periarticular bone loss as estimated by DXR in comparison to patients with methotrexate plus placebo. In addition, patients with clinical remission and ACR70-Response revealed no periarticular demineralisation.
30927978 Myeloid disorders after autoimmune disease. 2019 Mar Autoimmune diseases (ADs) are associated with an increased risk not only of lymphoproliferative disorders but also of myeloid malignancies. The excess risk of myelodysplastic syndromes and/or acute myeloid leukemia is observed across several AD types, including systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disorders, multiple sclerosis, among others. The risk of developing myeloid neoplasms (MNs) is dependent on several variables, including the specific AD type, chronicity and severity of the AD, type and duration of exposure of disease modifying anti-rheumatic drugs or cytotoxics/immunosuppressives, and genetic predisposition risk. Putative triggering factors linking AD to elevated MN risk include AD-directed medications, shared genetic susceptibilities between the two disease entities, and chronic immune stimulation or bone marrow infiltration by the AD. Molecular mechanisms underpinning leukemogenesis remain largely speculative and warrant further investigation. Leukemias arising in patients with AD are not always 'therapy-related' in that MNs may develop in certain AD subtypes even among patients with no prior therapy exposure. Only a few studies have attempted to determine factors associated with MN development in AD but failed to demonstrate consistent characteristic clinical or paraclinical features. These reports have failed to demonstrate a clear correlation between individual agent exposure and subsequent leukemia development due to the low rates of therapy exposure compounded by the rarity of MN occurrence. Notwithstanding, the leukemogenic potential is best documented with agents such as azathioprine, cyclophosphamide, and mitoxantrone; this risk of MN development does not appear to be shared by biologic approaches such as anti-tumor necrosis factors-alpha inhibitors. In this article, we discuss plausible biologic mechanisms underlying MN pathogenesis in AD and review the data available on the development of MNs in patients with AD.
31862930 Shoulder tenderness was associated with the inflammatory changes on magnetic resonance ima 2019 Dec 20 The aim of this study was to assess the association between the shoulder tenderness and the inflammatory changes on magnetic resonance imaging (MRI) in the rheumatoid shoulder. Forty-one shoulders of 41 patients with rheumatoid arthritis (RA) were examined. We evaluated synovitis, erosion and bone marrow edema, by counting the numbers of each positive site, and rotator cuff tears on shoulder MRI. The association between the shoulder tenderness and the MRI findings were statistically analyzed. Twenty-three of 41 patients had tenderness in the shoulder joints. There were 20 shoulders (48.8%) with rotator cuff tear, and no significant difference was observed in the prevalence of rotator cuff tear between the tenderness group and non-tenderness group (p = 0.080). There were no significant differences in the demographic data between these two groups. In MRI findings, we found significant difference for the synovitis (p = 0.001) and bone marrow edema (p = 0.021). Synovitis was strongly associated with the shoulder tenderness (OR: 3.996, 95% CI: 1.651-9.671). Synovitis was the factor most associated with shoulder tenderness.
30809900 Simple and rapid analysis of tocilizumab using HPLC-fluorescence detection method. 2019 May We developed a novel assay using high-performance liquid chromatography (HPLC) with fluorescence detection for the determination of tocilizumab (TCZ), after it has undergone a facile and rapid pretreatment. TCZ belongs to the same subclass as IgG1 (Immunoglobulin G subclass 1), and we could separate TCZ from IgG1 without antigen-antibody reactions, with the novel detection method. The separation of these antibodies was achieved by pretreatment with an organic solvent containing a base, such as trimethylamine and triethylamine. The effect of these bases on the separation of TCZ is related to the hydrophobicity of the base rather than the electrostatic charge. The results indicated that the surface charge of antibodies changed because of the structural change, even though the difference in the amino acid sequences of the antibodies was very low. Our method is available for the separation of the antibody subclasses, and it would be useful to assay TCZ in blood.
31880128 [Analysis of Periodontal Status and Salivary Microbial Diversity in Patients with Rheumato 2019 Dec OBJECTIVE: To observe the periodontal status and salivary microbial diversity in patients with rheumatoid arthritis, and to analyze the relationship between the composition of oral microflora in patients with RA and the incidence of rheumatoid arthritis. METHODS: 24 patients who were diagnosed as rheumatoid arthritis were enrolled in the experimental group, and 20 healthy persons were enrolled in the control group. The periodontal index was recorded and non-irritating saliva was collected. DNA was extracted and high-throughput sequencing was performed. RESULTS: There were no significant differences in periodontal indices between the RA group and the control group. After analysis of salivary microorganisms in RA patients and control group, there was no significant difference in salivary microbial diversity between RA patients and control group. At the phylum level, 13 phyla were found, including Firmicutes (30.2%), Proteobacteria (29.3%), Bacteroidetes (23.8%), Fusobacteria (7.3%), Actinobacteria (5.6%) as dominant bacteria. Bacteroidetes (P=0.04) and spirochoetes (P=0.01) were significantly higher in the RA group. A total of 144 genus were found, and 12 dominant genus were found. 11 genuses were found to have significant difference between the RA group and the control. At the genus level, Prevotella (P=0.03), Porphyromonas (P=0.005 7), Tannerella (P=0.001 9) and Treponema (P=0.010) were significantly higher in the RA group. Salivary microbial community similarity in the RA group was significantly higher than that in the control group. CONCLUSION: Compared with healthy people, RA patients had higher periodontal inflammation indices, but there was no statistical difference. The oral saliva of patients with rheumatoid arthritis has a unique microbial diversity structure. This result provides a new insight for understanding the pathogenesis of rheumatoid arthritis.
31284792 Role of redox imbalance and cytokines in mediating oxidative damage and disease progressio 2019 Jul Rheumatoid arthritis (RA) is a systemic inflammatory autoimmune disorder wherein the contributory role of oxidative stress has been established in the synovial fluid. As availability of synovial fluid is limited, this study aimed to evaluate in the peripheral blood of patients with RA, the relationship if any, between the extent of oxidative stress in terms of generation of reactive oxygen species (ROS) in neutrophils, plasma NADPH oxidase and myeloperoxidase activity with markers of oxidative damage, circulating cytokines and disease activity score (DAS28). In patients with RA, neutrophils in peripheral blood demonstrated an enhanced generation of ROS, coupled with depletion of free radical scavenging activity. Furthermore, the NADPH oxidase and myeloperoxidase activity was enhanced as were markers of damage. There was a positive correlation between the DAS 28 and generation of ROS, NADPH oxidase and myeloperoxidase activity as also with oxidative stress mediated protein carbonylation. Patients with RA demonstrated an increase in proinflammatory (IL-17, IL-23, and IFN-γ) and some anti-inflammatory (IL-4, IL-5, and TGF-β) cytokines. Although the levels of IL-17 correlated positively with generation of ROS, myeloperoxidase, markers of protein damage and DAS28, IL-23 correlated positively only with protein damage, and negatively with free radical scavenging activity. Importantly, incubation of neutrophils from healthy donors with plasma or SF from patients with RA translated into an enhanced generation of ROS, along with an elevation of intracellular proinflammatory cytokines. Taken together, in patients with RA, circulating neutrophils mediated a shift in the oxidant/antioxidant balance favouring the former, which translated into protein damage and contributed towards disease progression.
30861334 Efficacy and safety of add-on tacrolimus versus leflunomide in rheumatoid arthritis patien 2019 Jun AIM: To investigate the efficacy and safety of tacrolimus (TAC) versus leflunomide (LEF) when combined with methotrexate (MTX) in rheumatoid arthritis (RA) patients. METHOD: This was a 24-week multi-center, double-blind, randomized, non-inferiority study targeting RA patients with moderate to severe Disease Activity Score of 28 joints (DAS28 > 3.2) who showed inadequate response to MTX. Patients were randomized into TAC or LEF (add-on to MTX) groups. Initial daily doses of TAC and LEF were 1.5 and 10 mg, respectively, for 4 weeks and then doubled until the end of the study. The primary endpoint was DAS28 comparison at 24 weeks. RESULTS: Eighty-seven patients were screened in 10 centers and 75 patients were randomized into two groups. Baseline demographics were comparable between TAC + MTX and LEF + MTX groups. The TAC + MTX group was non-inferior to the LEF + MTX group in terms of DAS28 at 24 weeks (mean difference of DAS28: -0.1812, 95% confidence interval: -0.8073, 0.4450). There was a greater number of adverse events in the LEF + MTX group (66 in LEF + MTX and 49 in TAC + MTX). Six patients presented with transaminitis in the LEF + MTX group compared with two patients in the TAC + MTX group. CONCLUSION: The efficacy of TAC combined with MTX was non-inferior to LEF + MTX. It had a reasonable safety profile in RA patients with moderate to severe disease activity (http://cris.nih.go.kr; KCT0000781).