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ID PMID Title PublicationDate abstract
32377539 Serum Neuropeptide Y Levels Are Associated with TNF-α Levels and Disease Activity in Rheu 2020 BACKGROUND: Neuropeptide Y (NPY) is a sympathetic neurotransmitter with effects on the regulation of inflammatory cells. The role of NPY on autoimmune inflammatory diseases such as rheumatoid arthritis (RA) is not completely understood. Therefore, we evaluate if NPY levels are markers of disease activity in RA and if there is a correlation between NPY levels and tumor necrosis factor-alpha (TNF-α), leptin, and interleukin 6 (IL-6) levels. METHODS: Cross-sectional design, including 108 women with RA. We assessed disease activity by DAS28-ESR (considering active disease a score of ≥2.6). Serum NPY levels and anti-CCP2 antibody, TNF-α, IL-6, and leptin levels were quantified (ELISA). RESULTS: Sixty-eight RA had an active disease (RA-active), and 40 were in remission (RA-remission). RA-active patients had higher NPY levels vs. RA-remission (22.8 ± 13.6 vs. 17.8 ± 10.3; p = 0.04). NPY levels correlated with increased TNF-α levels (r = 0.32, p = 0.001). Leptin or IL-6 did not correlate with NPY levels. In the logistic regression analysis, NPY increased the risk of disease activity (OR: 1.04, 95% CI 1.006-1.09, and p = 0.03). CONCLUSION: Higher NPY levels are an independent marker of disease activity in RA. This study encourages the quantification of NPY levels as a surrogate marker for RA-active. Future studies evaluating the role of NPY levels interacting with other proinflammatory cytokines are required.
32092739 Primary culture of mouse adipose and fibrous synovial fibroblasts under normoxic and hypox 2020 Synovial fibroblasts have attracted considerable attention in studies of joint diseases. Although mice are useful and powerful in in vitro and in vivo experiments, primary cultures of mouse synovial fibroblasts are notoriously difficult because the mouse synovial tissues are much smaller and cell cycle arrests can be induced more easily in murine cells than in human cells. Here, we report a precise protocol for the isolation and culture of fibroblasts from mouse adipose and fibrous knee joint synovia. In both adipose and fibrous synovial fibroblasts, proliferation was decreased in addition to a higher rate of cellular senescence under normoxic conditions (20% O(2)); however, it was maintained over 20 days with low cellular senescence under hypoxic conditions (3% O(2)). The marker gene expression in adipose and fibrous synovial fibroblasts was not markedly altered after a 3-week culture. Both cells displayed similar potencies for chondrogenic, osteogenic, and adipogenic differentiation, and responses to a proinflammatory cytokine. The present method provides a sufficient amount of mouse synovial fibroblasts for in vitro and in vivo experiments in joint biology and the pathophysiology of osteoarthritis and rheumatoid arthritis.
32565114 Protective effect of Ganoderic acid A on adjuvant-induced arthritis. 2020 Oct The purpose of the experiment was to explore the effect of Ganoderic acid A (GAA) on adjuvant-induced arthritis in rats. In this study, the rat model of collagen-induced rheumatoid arthritis (CIA) was established with type II collagen plus Freund's complete adjuvant. Arthritis index, joint pathology, toe swelling, hemorheology, synovial cell apoptosis, related cytokines and JAK3/STAT3 and nuclear factor-κB (NF-κB) signaling pathway were measured in rats. We found that GAA can significantly inhibit the arthritis index, improve joint pathology, reduce toe swelling, improve blood rheology, improve synovial cell apoptosis, and restore related cytokine negative regulation JAK3/STAT3 and NF-κB signaling pathways. In conclusion, GAA has an obvious therapeutic effect on joint inflammation of toes in CIA model rats, which may be due to the regulation of JAK3/STAT3 and NF-κB signaling pathway.
31504966 Joint microwave radiometry for inflammatory arthritis assessment. 2020 Apr 1 OBJECTIVES: Increased in-depth joint temperature measured by the rapid, easy-to-perform microwave radiometry (MWR) method may reflect inflammation, even in the absence of clinical signs. We hypothesized that MWR is useful for RA and spondyloarthritis patients' assessment. METHODS: Clinical examination, joint ultrasound and/or MRI and MWR were performed in two independent patient-control cohorts (n = 243). RESULTS: Among single RA joints MWR performed best in the knee using ultrasound as reference, with 75% sensitivity-73% specificity for grey-scale synovitis score ⩾2, and 80% sensitivity-82% specificity for power Doppler positivity. A stronger agreement was evident between increased knee relative temperature (Δt) and power Doppler positivity (82%) than with clinical examination (76%). In a different patient cohort with painful knees, a knee Δt ⩽0.2 predicted power Doppler positivity with 100% positive and negative predictive values. A thermo-score summing 10 Δt values of three large and seven small RA joints (elbow, knee, ankle, wrist, four hand and two foot joints of the clinically dominant arm or hand and leg or foot) correlated with ultrasound scores of synovitis/tenosynovitis (all P < 0.001) and the 28-joint Disease Activity Score (DAS28) (P = 0.004). The agreement of the thermo-score with ultrasound-defined joint inflammation (82%) was stronger than with DAS28 (64%). The thermo-score improved significantly after 90 days of treatment in patients with active RA at baseline (P = 0.004). Using MRI as reference, Δt of sacroiliac joints could discriminate between spondyloarthritis patients with or without sacroiliitis with 78% sensitivity-74% specificity. CONCLUSION: In-depth increased MWR-derived joint temperature reflects both subclinical and clinically overt inflammation and may serve as a biomarker in arthritis.
32306287 Serum CRP, MDA, Vitamin C, and Trace Elements in Bangladeshi Patients with Rheumatoid Arth 2021 Jan Rheumatoid arthritis (RA) is an autoimmune disorder that is a painful health crisis. This study aimed to assess the serum C-reactive protein (CRP), malondialdehyde (MDA), non-enzymatic antioxidant (vitamin C), and trace elements (Zn, Cu, Mn, and Fe) in RA patients, and thereby correlate these parameters with the association of RA. This study included 20 Bangladeshi RA patients and 20 normal healthy volunteers as control subjects. CRP level was determined using a laboratory-based latex agglutination-enhanced immunoassay. The lipid peroxidation level was determined by measurement of the serum level of MDA. Non-enzymatic antioxidant vitamin C was assessed by UV spectrophotometric method. Trace elements were determined by atomic absorption spectroscopy (AAS). Our study observed significantly higher concentrations of CRP (p < 0.001) and MDA (p < 0.001), and significantly lower concentrations of vitamin C (p < 0.001) in the RA patient. The mean values of Zn, Cu, Mn, and Fe were 6.62 ± 0.34, 1.42 ± 0.17, 7.51 ± 0.23, and 29.25 ± 0.41 ppm for the RA patients respectively and 13.57 ± 9.13, 1.15 ± 0.17, 1.59 ± 0.18, and 62.47 ± 5.25 ppm for the control subjects, consequently. There was a significant difference (p < 0.05) in the trace element levels between the RA patients and control subjects. Our study suggests that a higher concentration of CRP and MDA, lower levels of vitamin C, and altered trace elements may be linked to RA.
32796045 Clinical outcomes of hospitalised patients with COVID-19 and chronic inflammatory and auto 2020 Dec OBJECTIVES: The impact of inflammatory rheumatic diseases on COVID-19 severity is poorly known. Here, we compare the outcomes of a cohort of patients with rheumatic diseases with a matched control cohort to identify potential risk factors for severe illness. METHODS: In this comparative cohort study, we identified hospital PCR+COVID-19 rheumatic patients with chronic inflammatory arthritis (IA) or connective tissue diseases (CTDs). Non-rheumatic controls were randomly sampled 1:1 and matched by age, sex and PCR date. The main outcome was severe COVID-19, defined as death, invasive ventilation, intensive care unit admission or serious complications. We assessed the association between the outcome and the potential prognostic variables, adjusted by COVID-19 treatment, using logistic regression. RESULTS: The cohorts were composed of 456 rheumatic and non-rheumatic patients, in equal numbers. Mean age was 63 (IQR 53-78) years and male sex 41% in both cohorts. Rheumatic diseases were IA (60%) and CTD (40%). Most patients (74%) had been hospitalised, and the risk of severe COVID-19 was 31.6% in the rheumatic and 28.1% in the non-rheumatic cohort. Ageing, male sex and previous comorbidity (obesity, diabetes, hypertension, cardiovascular or lung disease) increased the risk in the rheumatic cohort by bivariate analysis. In logistic regression analysis, independent factors associated with severe COVID-19 were increased age (OR 4.83; 95% CI 2.78 to 8.36), male sex (1.93; CI 1.21 to 3.07) and having a CTD (OR 1.82; CI 1.00 to 3.30). CONCLUSION: In hospitalised patients with chronic inflammatory rheumatic diseases, having a CTD but not IA nor previous immunosuppressive therapies was associated with severe COVID-19.
32508840 Enhanced Pro-apoptotic Effects of Fe(II)-Modified IVIG on Human Neutrophils. 2020 Mild modification of intravenous immunoglobulin (IVIG) has been reported to result in enhanced polyspecificity and leveraged therapeutic effects in animal models of inflammation. Here, we observed that IVIG modification by ferrous ions, heme or low pH exposure, shifted the repertoires of specificities in different directions. Ferrous ions exposed Fe(II)-IVIG, but not heme or low pH exposed IVIG, showed increased pro-apoptotic effects on neutrophil granulocytes that relied on a FAS-dependent mechanism. These effects were also observed in human neutrophils primed by inflammatory mediators or rheumatoid arthritis joint fluid in vitro, or patient neutrophils ex vivo from acute Crohn's disease. These observations indicate that IVIG-mediated effects on cells can be enhanced by IVIG modification, yet specific modification conditions may be required to target specific molecular pathways and eventually to enhance the therapeutic potential.
31897527 Acute Effects of Glucocorticoid Treatment, TNFα or IL-6R Blockade on Bone Turnover Marker 2020 Apr Tumor Necrosis Factor (TNF)-α and Interleukin (IL)-6 play a fundamental role in bone loss in rheumatoid arthritis (RA), partly due to the inhibition of the Wnt canonical pathway. The aim of our study was to investigate the short-term effects of three different treatments on Wnt inhibitors (Dkk-1 and sclerostin) and on bone turnover markers (BTMs): N-propeptide of type I collagen (PINP) and C-terminal telopeptide of type I collagen (β-CTX-I). We performed a retrospective analysis of prospectively collected data. We enrolled women affected by early RA (< 12 months) with active disease (DAS28 ≥ 2.6) despite a 6-month treatment with methotrexate (10-15 mg/week), who then started certolizumab pegol, tocilizumab, or methyl-prednisolone (8 mg/daily). Patients were divided into three groups according to the treatment. Blood samples were collected at baseline, week 1, and week 4. We selected 14 patients treated with certolizumab pegol, 14 patients with tocilizumab, and 20 patients with methyl-prednisolone. No difference between any of the tested parameters was found at baseline. β-CTX-I, Dkk-1, and sclerostin decreased after 1 week of treatment with certolizumab pegol (- 27% ± 21.5, - 50% ± 13.2, and - 30% ± 30.4, respectively, p < 0.05). Methyl-prednisolone induced similar changes, albeit less marked, on β-CTX-I and Wnt inhibitors, with a decrease in PINP (- 16.1% ± 16.5, p < 0.05). Tocilizumab did not significantly affect BTMs or Wnt inhibitors. No significant changes were found for PTH and 25OHD. In the first four weeks of treatment, TNFα inhibition showed strong effects on BTMs and Wnt inhibitors, differently from IL-6 blockade. Glucocorticoids induced similar changes; nonetheless, they showed undesired effects on bone formation.
32955037 Correlation between sarcopenia and nailfold microcirculation, serum 25-hydroxycholecalcife 2021 Sep AIMS: To investigate the correlation between sarcopenia and nailfold microcirculation and serum 25-hydroxycholecalciferol [25 (OH) D3] (instead of 25-hydroxyvitamin D) and IL-17 levels in female rheumatoid arthritis (RA) patients. METHODS: 130 female rheumatoid arthritis (RA) patients and 80 healthy controls were tested. Nailfold capillaroscopic scores (NFCS) were measured. Bioimpedance analysis (BIA) was used to measure skeletal muscle mass. Enzyme-linked immunosorbant assay (ELISA) was used to detect the levels of IL-17, IL-6 and TNF-α. Serum 25 (OH) D3 concentration was determined by photochemical immunoassay. The correlation was analyzed by Pearson's correlation, and the influencing factors were analyzed by binary logistic regression. RESULTS: (1) Compared with the control group, NFCS and serum IL-17 levels were higher in the RA group, while the serum 25 (OH) D3 and skeletal mass index (SMI) were lower. (2) Pearson correlation analysis found: SMI was positively correlated with 25 (OH) D3 (r=0.515, P<0.001), SMI was negatively correlated with IL-17 (r=-0.468, P<0.001), SMI was negatively correlated with NFS (r = -0.229, P=0.009); (3) Logistic regression analysis: serum 25 (OH) D3 was a protective factor for sarcopenia (OR=0.392, P=0.016); IL-17, C-reactive protein, and NFS were risk factors for sarcopenia (OR=1.516, P=0.049; OR=1.469, P=0.045; OR=3.497, P=0.002). CONCLUSION: Secondary sarcopenia in RA is common and is closely related to microcirculation abnormalities. Increased NFCS is a risk factor for sarcopenia. Decreased serum 25 (OH) D3 levels and increased IL-17 are also risk factors for sarcopenia, but the mechanisms involved in sarcopenia and microcirculation abnormalities need further investigation.
33463128 MicroRNAs as the Important Regulators of T Helper 17 Cells: A Narrative Review. 2020 Dec 19 T helper (Th)-17 cells are a distinct and important subset of Th cells and their functions are due to the ability of production and secretion of key cytokines in the immune system such as interleukin (IL)-17, IL-22, IL-21, and tumor necrosis factor-α (TNF-α). According to these cytokines, these cells have vital roles in the pathogenesis of the disease such as rheumatoid arthritis (RA) and osteoarthritis (OA). Nowadays, microRNAs (miRNAs) are defined as essential regulators of cell function by targeting transcription factors and other elements that act in cells to control gene expression. The purpose of this study was to detect and investigate articles evaluating the function of miRNA in Th-17 cell performance. The language was restricted to English and the search was done in PubMed, Web of Science and Embase. In this review, we first explain the role of effective factors in the function of Th17 lymphocytes, and then, we summarize the performance of several miRNAs involved in the activation and appropriate functions of Th17 cells in the immune system.
33349110 Drug-induced subacute cutaneous lupus erythematosus associated with abatacept. 2021 Apr Numerous drugs have been linked to the induction or exacerbation of systemic cutaneous lupus erythematosus (SCLE). This report presents the third case of the biologic abatacept as an exacerbating medication for SCLE. A 73-year old woman with a remote history of subacute cutaneous lupus and rheumatoid arthritis, well controlled on hydroxychloroquine, presented with worsening annular erythematous, slightly scaly plaques on her forearms and hands. She had been started on abatacept a month prior. She was diagnosed with SCLE exacerbated by abatacept given the clinical findings, time course, and skin biopsy with interface dermatitis. Her skin eruption cleared completely several months later after discontinuing abatacept and switching to tociluzumab, while remaining on hydroxychloroquine. This case highlights the need to consider abatacept as a potential exacerbating medication for SCLE in any patient with a new photodistributed papulosquamous eruption.
31919575 Positive conversion of interferon-γ release assay in patients with rheumatic diseases tre 2020 Mar The objective of this study is to investigate whether the type of biologics (TNFi or others) or type of rheumatic diseases (RA or AS) influence the conversion rate of initially negative tuberculosis (TB) screening test results. A total of 119 patients with RA or AS who had negative baseline interferon-γ release assay (IGRA) results assessed by QuantiFERON-TB Gold in tube (QTF-GIT) were included. All patients received biologic agents, and rescreening with QTF-GIT was performed after a median of 25.9 months from the baseline test. Clinical characteristics and IFN-γ levels were compared between converters and non-converters. Logistic regression analysis was performed to identify factors associated with positive conversion. IGRA conversion was found in 14 of 119 patients (11.8%). The converters were older (53.4 ± 14.2 vs 44.4 ± 15.5 years, p = 0.040), had higher baseline TB-specific IFN-γ responses (0.105 [0.018-0.205] vs 0.010 [0.000-0.035] IU/ml, p = 0.001) and higher incidence of active TB (14.3% vs 0.0%, p = 0.013). The number of patients with RA or AS was 9 (64.3%) or 5 (35.7%) in converters, and 45 (42.9%) or 60 (57.1%) in non-converters. In terms of use of biologics, TNFi of monoclonal antibody form was less commonly used in the converters (p = 0.024). In the logistic regression analysis, type of disease and type of biologics used were not associated with IGRA conversion, whereas baseline TB-specific IFN-γ response was significantly associated with IGRA conversion (OR 1.083, 95% CI 1.019-1.151, p = 0.011). Serial monitoring of LTBI with IGRA retesting is needed during biologic treatment, regardless of the type of rheumatic diseases or type biologics used.
33371095 Rheumatoid arthritis patients with peripheral blood cell reduction should be evaluated for 2020 Dec 18 RATIONALE: Felty syndrome is a rare and life-threatening type of rheumatoid arthritis (RA). PATIENT CONCERNS: A patient with RA had skin rash and subcutaneous hemorrhage, with a significant decrease in blood hemoglobin (Hb), white blood cell count (WBC), and blood platelet count (BPC). DIAGNOSES: The patient had a history of RA, splenomegaly, decreased Hb, WBC, BPC, and normal immunological indexes, combined with a series of bone marrow related tests and genetic tests. INTERVENTIONS: She was given high-doses of glucocorticoids intravenously, followed by oral prednisone and cyclosporine maintenance therapy. OUTCOMES: Her symptoms were resolved within 2 weeks after the start of immunosuppression. After 2 weeks of discharge, the Hb, WBC, BPC basically returned to normal, and prednisone gradually decreased. LESSONS: Felty syndrome is a rare complication of RA. Reductions in Hb, WBC, BPC, and subcutaneous hemorrhage should be considered strongly as the possibility of Felty syndrome. Multi-disciplinary diagnosis and related tests of bone marrow and genes are helpful for diagnosis and correct treatment.
33173951 Association of the DNASE1L3 rs35677470 polymorphism with systemic lupus erythematosus, rhe 2020 Dec Although genome‑wide association studies (GWAS) have identified hundreds of autoimmune disease‑associated loci, much of the genetics underlying these diseases remains unknown. In an attempt to identify potential causal variants, previous studies have determined that the rs35677470 missense variant of the Deoxyribonuclease I‑like 3 (DNASE1L3) gene was associated with the development of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and systemic sclerosis (SSc). DNase1L3 is a member of the human DNase I family, representing a nuclease that cleaves double‑stranded DNA during apoptosis and serving a role in the development of autoimmune diseases. The present study aimed to determine the role of the rs35677470 variant at the DNASE1L3 gene leading to the R206C mutation in SLE, RA and SSc. The underlying mechanism potentially affecting protein structure loss of function was also assessed. DNASE1L3 evolution was investigated to define conservation elements in the protein sequence. Additionally, 3D homology modeling and in silico mutagenesis was performed to localize the polymorphism under investigation. Evolutionary analysis revealed heavily conserved sequence elements among species, indicating structural/functional importance. In silico mutagenesis and 3D protein structural analysis also demonstrated the potentially varied impact of the DNASE1L3 (rs35677470) single nucleotide polymorphism (SNP), providing an explanation for its effect on the R206C variant. Structural analysis demonstrated that the rs35677470 SNP encodes a non‑conservative amino acid variation, R206C, which disrupted the conserved electrostatic network holding secondary protein structure elements in position. Specifically, the R206 to E170 interaction forming part of a salt bridge network stabilizing two α‑helices was interrupted, thereby affecting the molecular architecture. Previous studies on the effect of this SNP in Caucasian populations demonstrated lower DNAse1L3 activity levels, which is consistent with the current results. The present study comprehensively evaluated the shared autoimmune locus of DNASE1L3 (rs35677470), which produced an inactive form of DNaseIL3. Furthermore, structural analysis explained the potential role of the produced mutation by modifying the placement of structural elements and consequently introducing disorder in protein folding, affecting biological function.
32765511 Nicotine Changes the microRNA Profile to Regulate the FOXO Memory Program of CD8(+) T Cell 2020 Objective: Smoking suppresses PD-1 expression in patients with rheumatoid arthritis (RA). In this study, we assess if smoking changed the epigenetic control over CD8(+) T cell memory formation through a microRNA (miR) dependent mechanism. Methods: Phenotypes of CD8(+) T cells from smokers and non-smokers, RA and healthy, were analyzed by flow cytometry. A microarray analysis was used to screen for differences in miR expression. Sorted CD8(+) cells were in vitro stimulated with nicotine and analyzed for transcription of miRs and genes related to memory programming by qPCR. Results: CD27(+)CD107a(-)CD8(+) T cells, defining a naïve-memory population, had low expression of PD-1. Additionally, the CD27(+) population was more frequent in smokers (p = 0.0089). Smokers were recognized by differential expression of eight miRs. Let-7c-5p, let-7d-5p and let-7e-5p, miR-92a-3p, miR-150-5p, and miR-181-5p were up regulated, while miR-3196 and miR-4723-5p were down regulated. These miRs were predicted to target proteins within the FOXO-signaling pathway involved in CD8(+) memory programming. Furthermore, miR-92a-3p was differentially expressed in CD8(+) cells with naïve-memory predominance. Nicotine exposure of CD8(+) cells induced the expression of miR-150-5p and miR-181a-5p in the naïve-memory cells in vitro. Additionally, nicotine exposure inverted the ratio between mRNAs of proteins in the FOXO pathway and their targeting miRs. Conclusions: Smokers have a high prevalence of CD8(+) T cells with a naïve-memory phenotype. These cells express a miR profile that interacts with the memory programming conducted through the FOXO pathway.
33249645 Anti-citrullinated protein antibodies are associated with neutrophil extracellular trap fo 2021 Mar OBJECTIVES: We evaluated the associations of anti-citrullinated protein antibodies (ACPAs) and serological and cytological levels of neutrophil extracellular trap (NET) formation in rheumatoid arthritis (RA) patients. METHODS: Serum levels of myeloperoxidase-DNA and elastase-DNA complexes (NET remnants) were examined in 51 patients with RA and 40 healthy controls using a modified enzyme-linked immunosorbent assay. Neutrophils were isolated by density gradient centrifugation. IgG antibodies were purified by affinity chromatography. NET formation in RA and control neutrophils was assessed by microscopy in vitro. NETs were purified and co-incubated with fibroblast-like synoviocyte (FLS) cells. Interleukin (IL)-6 and IL-8 mRNA expression and protein levels in FLS cells were determined by real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. RESULTS: In RA patients, NET remnants in the peripheral circulation were higher in extremely high ACPA titers when compared to in moderate ACPA titers. And IgG antibodies containing ACPA can stimulate neutrophils to form NETs in a concentration-dependent manner. Furthermore, significantly higher expression of the pro-inflammatory cytokines IL-6 and IL-8 is detected after FLS cells interacted with NETs which derived from neutrophils stimulated with ACPA-containing IgG antibodies. CONCLUSIONS: Anti-citrullinated protein antibodies may enhance NET formation and contribute to inflammation development in RA by stimulating NET formation, such as by subsequent activation of FLS cells by NETs.
32967573 Subcutaneous immunoglobulin therapy in statin-induced necrotizing autoimmune myopathy. 2021 Jan We report a case of statin-associated necrotising autoimmune myopathy successfully treated with subcutaneous immunoglobulin therapy (SCIG) monotherapy without corticosteroids. This is a 51-year old female with seronegative rheumatoid arthritis, who had been on statins for several years, who developed proximal muscle weakness and elevated creatine kinase after resuming her statin post sleeve gastrectomy for weight loss. Our patient had a history of severe side effects to prednisone. She did not respond to mycophenolate, cyclophosphamide, and rituximab treatment. She had responded to partial treatment with intravenous immunoglobulin (IVIG) but had a severe headache after IVIG infusion. IVIG treatment was discontinued. We tried SCIG treatment, and she was able to tolerate the SCIG treatment with intermittent headaches that were less intense. After treatment with SCIG, creatine kinase levels decreased significantly, with an improvement of muscle strength. She continues to do well on SCIG treatment. To our knowledge, no other cases of statin-associated necrotising autoimmune myopathy treated with SCIG have been reported in the literature. More studies and reports are needed to confirm the utility and efficacy of SCIG in statin-associated necrotising autoimmune myopathy, as well as to provide information about dosing, tolerability, and durability of SCIG in the treatment of statin-associated necrotising autoimmune myopathy.
33423717 [Clinical Features of Relapsing Polychondritis Patients Presented with Arthropathy]. 2020 Dec 30 Objective To explore the clinical characteristics of relapsing polychondritis(RP)patients presented with arthropathy. Methods We retrospectively analyzed the clinical data of 201 RP patients who were hospitalized in our center between December 2005 and February 2019.After 16 patients with co-existing other autoimmune diseases and malignancies were ruled out,185 RP patients entered the final analysis,among whom 16 RP patients were presented with arthropathy and 169 without arthropathy.The demographic data,clinical manifestations,laboratory findings,and prognosis were compared between these two groups. Results Five of the 16 RP patients with arthropathy at presentation were misdiagnosed as rheumatoid arthritis.Compared with RP patients without arthropathy at presentation,RP patients with arthropathy at presentation had a longer disease course[(37.50±66.50)months vs.(9.00±11.00)months,z=-3.186,P =0.001],longer time of diagnostic delay[(24.00±41.25)months vs.(7.00±9.00)months,z=-2.890,P=0.004],and higher incidence of eye(62.50% vs. 36.09%,χ(2)=4.309,P=0.038)and nervous system involvements(43.75% vs. 15.38%,χ(2)=6.205,P=0.013). Conclusions RP patients with arthropathy at presentation are most likely to be misdiagnosed as rheumatoid arthritis.These patients are characterized by longer disease course and diagnostic delay and more frequrent eye and nervous system involvements.
31268376 Sarilumab monotherapy or in combination with non-methotrexate disease-modifying antirheuma 2020 Mar Objectives: To determine long-term safety and efficacy of sarilumab as monotherapy or with non-methotrexate (MTX) conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) in Japanese patients with active rheumatoid arthritis (RA).Methods: In this double-blind, randomized study (NCT02373202), patients received subcutaneous sarilumab 150 mg q2w (S150) or 200 mg q2w (S200) as monotherapy or with non-MTX csDMARDs for 52 weeks. The primary endpoint was safety.Results: Sixty-one patients received monotherapy (S150, n = 30; S200, n = 31) and 30 received combination therapy (S150 + csDMARDs, n = 15; S200 + csDMARDs, n = 15). Rates of treatment-emergent adverse events (TEAEs) were 83.3%/90.3%/93.3%/86.7% for S150/S200/S150 + csDMARDs/S200 + csDMARDs, respectively. Nasopharyngitis and neutropenia were the most frequently reported TEAEs. One serious infection was reported in each monotherapy group and in the S200 + csDMARDs group. There were no cases of grade 4 neutropenia; no patients with grade 3 neutropenia experienced associated serious infection. Improvements in ACR20/50/70 response rates were generally similar between the two monotherapy groups and between the two combination groups; improvements in physical function (Health Assessment Questionnaire-Disability Index, HAQ-DI) and DAS28-CRP were observed at weeks 24 and 52 (all groups).Conclusion: The safety profile of sarilumab was consistent with known class effects of interleukin-6 signaling blockade therapeutics. Sarilumab as mono- or combination therapy improved clinical signs/symptoms and physical function in Japanese RA patients.
32687015 Rapidly progressive glomerulonephritis after introduction of certolizumab pegol: a case re 2021 Jan Tumour necrosis factor (TNF) inhibitors are used against a variety of connective tissue diseases, including rheumatoid arthritis. Contrarily, although rare, TNF inhibitors are known to induce autoimmune diseases, such as systemic lupus erythematosus and psoriasis as a paradoxical reaction. We experienced a case of rapidly progressive glomerulonephritis after introduction of certolizumab pegol. The patient was a 30-year-old woman who was previously diagnosed with rheumatoid arthritis in X-8. She received treatment with methotrexate (8 mg/week) and infliximab (3 mg/kg/8 weeks), following which she showed low disease activity and remission. In September X-1, methotrexate and infliximab were discontinued and certolizumab pegol was introduced because she desired to bear children. In March X, the patient experienced renal dysfunction, and urinary protein analysis revealed positivity for myeloperoxidase anti-neutrophil cytoplasmic autoantibody. Renal biopsy showed crescentic glomerulonephritis, and the patient was diagnosed with rapidly progressive glomerulonephritis due to TNF inhibitor-induced microscopic polyangiitis. As she desired to bear children, rituximab was introduced in addition to corticosteroids, which led to remission of the symptoms. TNF inhibitors should be discontinued in patients who develop rapidly progressive glomerulonephritis, and these patients should be treated with immunosuppressive drugs, such as massive corticosteroids and cyclophosphamide. In the present case, rituximab was useful for not only the treatment, but also for the preservation of fertility.