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ID PMID Title PublicationDate abstract
30906224 Flemingia philippinensis Flavonoids Relieve Bone Erosion and Inflammatory Mediators in CIA 2019 BACKGROUND: The dry root of Flemingia philippinensis has been widely used in the treatment of rheumatism, arthropathy, and osteoporosis in traditional Chinese medicine; the therapeutic effects of Flemingia philippinensis are associated with antiarthritis in traditional Chinese medicine theory. This study was undertaken to investigate the mechanism of bone erosion protection and anti-inflammatory effect of Flemingia philippinensis flavonoids (FPF) in collagen-induced arthritis (CIA) in mice. METHODS: Flavonoids were extracted from the dry root of Flemingia philippinensis. Collagen-induced arthritis in C57BL/6 mice was used as a rheumatoid arthritis model, and the mice were orally fed with FPF prior to induction to mimic clinical prophylactic therapy for a total of 39 days. After treatment, histology and immunohistochemistry staining were performed, and the levels of anti-collagen type II (CII) antibody and inflammatory mediators, as well as the key proteins of nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways, were detected in the samples taken from ankle joints, plasma, and paws. RESULTS: FPF administration significantly suppressed the paw swelling and arthritic score in CIA mice. FPF reduced inflammatory infiltration and pannus formation, articular cartilage destruction and osteoclast infiltration, and the expression of MMP-9 and cathepsin K in the ankle joint. FPF inhibited plasma anti-CII antibody levels and the production of inflammatory cytokines and chemokines in CIA paws. FPF treatment suppressed the activation of NF-κB as indicated by downregulating the phosphorylation of NF-κB p65 and mitogen-activated protein kinases in CIA paws. Additionally, FPF significantly inhibited inflammation signaling by suppressing the activation of activator protein-1 subset and signal transducers and activators of transcription 3 (STAT3). CONCLUSIONS: Our data suggest that FPF might be an active therapeutic agent for rheumatoid arthritis and the preventive effect of FPF on arthritis is attributable to an anti-inflammatory effect on CIA by preventing bone destruction, regulating inflammatory mediators, and suppressing NF-κB and MAPK signaling pathways.
30687316 Plasma microRNA Profiles as a Potential Biomarker in Differentiating Adult-Onset Still's D 2018 Adult-onset Still's disease (AOSD) is a systemic inflammatory disease characterized by cytokine storm. However, a diagnostic test for AOSD in clinical use is yet to be validated. The aim of our study was to identify non-invasive biomarkers with high specificity and sensitivity to diagnosis of AOSD. MicroRNA (miRNA) profiles in PBMC from new-onset AOSD patients without any treatment and healthy controls (HCs) were analyzed by miRNA deep sequencing. Plasma samples from 100 AOSD patients and 60 HCs were used to validated the expression levels of miRNA by qRT-PCR. The correlations between expression levels of miRNAs and clinical manifestations were analyzed using advanced statistical models. We found that plasma samples from AOSD patients showed a distinct miRNA expression profile. Five miRNAs (miR-142-5p, miR-101-3p, miR-29a-3p, miR-29c-3p, and miR-141-3p) were significantly upregulated in plasma of AOSD patients compared with HCs both in training and validation sets. We discovered a panel including 3 miRNAs (miR-142-5p, miR-101-3p, and miR-29a-3p) that can predict the probability of AOSD with an area under the receiver operating characteristic (ROC) curve of 0.8250 in training and validation sets. Moreover, the expression levels of 5 miRNAs were significantly higher in active AOSD patients compared with those in inactive patients. In addition, elevated level of miR-101-3p was found in AOSD patients with fever, sore throat and arthralgia symptoms; the miR-101-3p was also positively correlated with the levels of IL-6 and TNF-α in serum. Furthermore, five miRNAs (miR-142-5p, miR-101-3p, miR-29c-3p, miR-29a-3p, and miR-141-3p) expressed in plasma were significantly higher in AOSD patients than in sepsis patients (P < 0.05). The AUC value of 4-miRNA panel (miR-142-5p, miR-101-3p, miR-29c-3p, and miR-141-3p) for AOSD diagnosis from sepsis was 0.8448, revealing the potentially diagnostic value to distinguish AOSD patients from sepsis patients. Our results have identified a specific plasma miRNA signature that may serve as a potential non-invasive biomarker for diagnosis of AOSD and monitoring disease activity.
31879015 Somatosensory profile of a patient with mixed connective tissue disease and Sjögren syndr 2020 Feb BACKGROUND AND OVERVIEW: The authors report the case of a patient with mixed connective tissue disease (MCTD) and Sjögren syndrome, showing signs and symptoms of bilateral trigeminal neuropathy and aseptic meningitis. The patient was assessed by means of quantitative sensory testing (QST) according to the German Research Network on Neuropathic Pain standards, in both the gingiva and forearm, and the results were compared with those of healthy control participants. CASE DESCRIPTION: A 27-year-old woman, who had received a diagnosis of MCTD and Sjögren syndrome from a rheumatologist, sought treatment at an orofacial pain clinic for bilateral electriclike pain in the maxillary anterior gingiva, eyelids, and cheeks. QST indicated allodynia and hyperalgesia in response to mechanical and thermal stimuli in both her gingiva and forearm, and cold hyperalgesia in her forearm only. She had been prescribed an oral corticosteroid (prednisone, 7 milligrams per day) by the rheumatologist, and was given lidocaine gel and systemic pregabalin (400 mg/d) at the clinic. CONCLUSIONS AND PRACTICAL IMPLICATIONS: The cause of trigeminal neuropathy in MCTD and Sjögren syndrome (SS) is unknown. The QST data in this case showed that the somatosensory disturbance severity was higher in the gingiva than in the forearm, suggesting that the trigeminal nerve may be more susceptible than other parts of the nervous system in patients with MCTD. If reproducible in future studies, the finding of greater hypersensitivity in the gingiva than in the forearm may provide an opportunity for dentists to play a role in the detection, diagnosis, or both of MCTD and SS. Dentists must be sufficiently familiar with MCTD and SS to include them in their differential diagnoses and should consider performing simple neurosensory testing such as via intraoral cotton swab or pinprick test.
31072030 Periodontal Health and Oral Microbiota in Patients with Rheumatoid Arthritis. 2019 May 8 This study aimed to investigate the periodontal health of patients with established rheumatoid arthritis (RA) in relation to oral microbiota, systemic and oral inflammatory mediators, and RA disease activity. Forty patients underwent full-mouth dental/periodontal and rheumatological examination, including collection of blood, saliva, gingival crevicular fluid (GCF) and subgingival plaque. Composition of plaque and saliva microbiota were analysed using 16S rRNA sequencing and levels of inflammatory mediators by multiplex-immunoassay. The majority of the patients (75%) had moderate or severe periodontitis and the rest had no/mild periodontitis. Anti-citrullinated protein antibody (ACPA) positivity was significantly more frequent in the moderate/severe periodontitis (86%) compared to the no/mild group (50%). No significance between groups was observed for RA disease duration or activity, or type of medication. Levels of sCD30/TNFRSF8, IFN-α2, IL-19, IL-26, MMP-1, gp130/sIL-6Rß, and sTNF-R1 were significantly higher in serum or GCF, and April/TNFSF13 was significantly higher in serum and saliva samples in moderate/severe periodontitis. The microbial composition in plaque also differed significantly between the two groups. In conclusion, the majority of RA patients had moderate/severe periodontitis and that this severe form of the disease was significantly associated with ACPA positivity, an altered subgingival microbial profile, and increased levels of systemic and oral inflammatory mediators.
30699195 Correction: Serum matrix metalloproteinase 3 levels are associated with an effect of igura 2019 [This corrects the article DOI: 10.1371/journal.pone.0202601.].
31849841 Impact of Rheumatoid Arthritis and Its Management on Falls, Fracture and Bone Mineral Dens 2019 Objectives: Rheumatoid arthritis (RA) is a systemic chronic inflammatory disease which presents with polyarthritis in addition to extra-articular manifestations. Historically, studies have shown a link between RA and adverse musculoskeletal outcomes but these studies were reported before the widespread use of biologic therapies. The aim of this study was therefore to investigate associations between RA, RA medications and bone mineral density, falls and fractures, using UK Biobank data. Methods: Diagnosis of RA was made using Hospital Episode Statistics (HES) ICD-10 coding. We assessed RA relationships with estimated bone mineral density (eBMD) from heel quantitative ultrasound measurements, self-reported falls (in last year) and HES recorded fracture, adjusted for age, ethnicity, BMI, smoking status, and physical activity. Results: Of 502,543 participants, 3849 (1.4%) of women and 1643 (0.7%) of men had a diagnosis of RA. Median age of the participants was 57 years (IQR 50-63) in women and 58 (IQR 50-64) in men. RA was associated with lower eBMD (men: β -0.244, 95% CI -0.378, -0.110 p < 0.001; women: β -0.217, 95% CI -0.297, -0.138 p < 0.001) a reported fall in the last year (men: OR 1.54, 95% CI 1.26, 1.87 p < 0.001; women: OR 1.36, 95% CI 1.19, 1.56 p < 0.001) and fracture in women (OR 1.76, 95% CI 1.43, 2.16 p < 0.001). Corticosteroid therapy in men (β -0.934, 95% CI -1.565, -0.304 p = 0.004) and disease modifying anti-rheumatic drug (DMARD) use in both sexes (men: β -0.437, 95% CI -0.761, -0.112 p = 0.008; women: β -0.243, 95% CI -0.421, -0.065 p = 0.007), but not biologic therapy, were associated with a lower eBMD with RA. Conclusions: RA was associated with lower eBMD, increased falls and fracture. Corticosteroid and DMARD therapy, but not biologic therapy, were associated with lower eBMD.
31223606 Incidence and Mortality of Osteoporotic Fracture in Rheumatoid Arthritis in South Korea Us 2019 May BACKGROUND: To investigate incidence and mortaltiy of osteoporotic fractures (including hip, spine, distal radius, and proximal humerus) in rheumatoid arthritis (RA) patients and compare them with those in the genearal population. METHODS: Data provided by National Health Insurance Service were used to identify osteoporotic fractures in patients aged >50 years between 2010 and 2012. Patients with RA were identified by the diagnostic code for seropositive RA. Standardized mortality ratios (SMRs; observed/expected deaths) of osteoporotic fractures were calculated based on age and gender-specific rates in the entire Korean population. Incidence, mortality, and SMR of osteoporotic fractures in RA patients and the general population were calculated and compared. RESULTS: Osteopororic fractures in the general population and RA patients were increased by 11.6% and 17.4% over 3 years (195,271 and 1,356 in 2010; 217,985 and 1,592 in 2012), respectively. Mean age-specific incidence of osteoporotic fracture in women and men with RA increased from 932.1/100,000 and 306.1/100,000 for aged 50 to 59 year to 9,377.0/100,000 and 3,700.9/100,000 for aged ≥80 years, respectively. Cumulative mortality rate in the first year after osteoporotic fracture in patients with RA was higher than that in the general population (7.8% in RA and 6.6% in the general population). SMR of osteoporotic fracture in RA patients was 1.4 times higher in men and 1.3 times higher in women than that for the general population. CONCLUSIONS: This study demonstated that incidence, 1-year mortality, and SMR of osteoporotic fracture in RA patients aged 50 years and older were higher than those in the general papulation.
30783427 Experimental study of TNF-α receptor gene transfection by ultrasound-targeted microbubble 2019 Mar Ultrasound-targeted microbubble destruction (UTMD) is a novel method for gene transfection. The aim of the present study was to identify the most suitable method of tumor necrosis factor (TNF)-α receptor (TNFR) gene transfection using UTMD for systemically treating a rat model of collagen-induced arthritis (CIA). Plasmids encoding the TNFR and enhanced green fluorescent protein (EGFP) with or without microbubbles were locally injected into the skeletal muscle and synovial membrane of CIA rats. The rats were divided into the following 6 groups: i) Group 1, plasmid + microbubble + ultrasound (muscle group); ii) group 2, plasmid + microbubble + ultrasound (joint group); iii) group 3, plasmid + ultrasound; iv) group 4, plasmid + microbubble; v) group 5, plasmid only and; vi) group 6, untreated controls. Rats were sacrificed at 2, 4 and 8 weeks of treatment. The transfection efficiency of the plasmids in the muscle or synovium was observed by fluorescence microscopy. Arthritis scores were calculated and serum levels of TNF-α were measured prior to and following treatment. Bilateral ankle joints were obtained and stained to observe synovial inflammation and the expression of TNF-α. EGFP expression was detected in all treated groups at each time point, and the fluorescence intensity of groups 1 and 2 was significantly greater than that of the other groups (P<0.05). For groups 1 and 2, the reductions in joint scores and serum levels of TNF-α were significant compared with the other groups (P<0.05). The number of synovial inflammatory cells and the synovial expression of TNF-α presented similar results among all experimental groups and no significant difference was observed between groups 1 and 2. Therefore, the results of the present study suggest that UTMD significantly enhanced the efficiency of TNFR gene transfection in the muscle and inflamed synovium of rats with. Regardless of whether the transfected TNFR gene was injected into the muscle or joint, it was continuously expressed in the rats for at least 8 weeks, which may improve arthritic symptoms and reduce the levels of inflammatory factors in the synovial tissues and peripheral blood.
30669892 Pain and affective distress in arthritis: relationship to immunity and inflammation. 2019 May Most arthritides are associated with pain and psychological distress (clinically significant depression and anxiety). Pain and depression are mutually exacerbating; both may continue even when joint involvement appears well controlled. Area covered: There is strong evidence that arthritis-related stress impacts the central nervous system and, together with peripheral inflammatory changes, can cause central sensitization that can lead to chronic pain and worsening of affective distress. Cytokines and chemokines participate both in joint inflammation and in central sensitization. We review evidence of these relationships in five arthritides, namely rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, gout, and in osteoarthritis of the hips and knees. Central sensitization in these conditions results in long-lasting pain and psychological distress. Expert commentary: Chronic pain and depression are important but often neglected in the clinical assessment and treatment of arthritis. The potential role of biologic cytokines and Janus kinase inhibitors in dealing with these symptoms needs further study.
31387650 Tofacitinib facilitates the expansion of myeloid-derived suppressor cells and ameliorates 2019 Aug 6 BACKGROUND: Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is a sometimes life-threatening complication in RA patients. SKG mice develop not only arthritis but also an ILD resembling RA-ILD. We previously reported that tofacitinib, a JAK inhibitor, facilitates the expansion of myeloid-derived suppressor cells (MDSCs) and ameliorates arthritis in SKG mice. The aim of this study was to elucidate the effect of tofacitinib on the ILD in SKG mice. METHODS: We assessed the effect of tofacitinib on the zymosan (Zym)-induced ILD in SKG mice histologically and examined the cells infiltrating the lung by flow cytometry. The effects of lung MDSCs on T cell proliferation and Th17 cell differentiation were assessed in vitro. We also evaluated the effects of tofacitinib on MDSCs and dendritic cells in vitro. RESULTS: Tofacitinib significantly suppressed the progression of ILD compared to the control SKG mice. The MDSCs were increased, while Th17 cells, group 1 innate lymphoid cells (ILC1s), and GM-CSF+ILCs were decreased in the lungs of tofacitinib-treated mice. MDSCs isolated from the inflamed lungs suppressed T cell proliferation and Th17 cell differentiation in vitro. Tofacitinib promoted MDSC expansion and suppressed bone marrow-derived dendritic cell (BMDC) differentiation in vitro. CONCLUSION: Tofacitinib facilitates the expansion of MDSCs in the lung and ameliorates ILD in SKG mice.
31221884 Use of prescription opioids among patients with rheumatic diseases compared to patients wi 2019 Jun 19 OBJECTIVE: Long-term opioid prescribing has increased amid concerns over effectiveness and safety of its use. We examined long-term prescription opioid use among patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), psoriatic arthritis (PsA) and ankylosing spondylitis (AS), compared with patients with hypertension (HTN). METHODS: We used Truven MarketScan, a US commercial claims database (2003-2014) and identified RA, SLE, PsA and AS cohorts, each matched by age and sex to patients with HTN. We compared long-term opioid prescription use during 1 year of follow-up and used multivariable Poisson regression model to estimate the relative risk (RR) of receiving opioid prescriptions based on underlying disease cohort. RESULTS: We identified 181 710 RA (mean age 55.3±13.1, 77% female), 45 834 SLE (47.1±13.1, 91% female), 30 307 PsA (49.7±11.5, 51% female), 7686 AS (44.6±12.0, 39% female) and parallel numbers of age-matched and sex-matched patients with HTN. The proportion of patients receiving long-term opioid prescriptions, and other measures of opioid prescriptions were higher among rheumatic disease cohorts and highest in patients with AS. AS was associated with the highest RR of receiving long-term opioid prescriptions (RR 2.73, 95% CI 2.60 to 2.87) versus HTN, while RRs were 2.21 (2.16 to 2.25) for RA, 1.94 (1.87 to 2.00) for PsA and 1.82 (1.77 to 1.88) for SLE. CONCLUSIONS: Patients with rheumatic disease have higher rates of long-term opioid prescriptions, and patients with AS have the highest risk of receiving opioid prescriptions versus patients with HTN. Further studies investigating the effectiveness of disease-targeted treatments on decreasing opioid use in these four rheumatic diseases may provide strategies for reducing prescription opioids.
31791669 Assisted reproductive technologies for women with rheumatic AID. 2020 Apr Assisted reproductive technology (ART) procedures are safe for women with rheumatic autoimmune diseases (rAID) when illness is inactive. Medications incompatible with pregnancy should be replaced with alternative pregnancy-compatible medications months before planned ART procedures to allow time to verify the substitute medication's efficacy and tolerability. Medications compatible with pregnancy should be continued, as should anticoagulation (warfarin changed to low-molecular-weight heparin) before pregnancy begins. Protocols that provide details for specific medications are available. All patients with rAID should be screened for diagnosis-relevant organ system damage, and those intending to carry their own pregnancies must be tested for aPL and anti-Ro/La autoantibodies. Patients with organ damage and/or positive tests for aPL and anti-Ro/La should be counseled about fetal and maternal risks, including implications to the child and family of maternal disability or death. Sperm donors with rAID may need to discontinue medications. REI and physicians treating patients with rAID (usually rheumatologists) must work together to plan and accomplish ART.
31122078 Development of a Retro-Odontoid pseudotumor in the absence of atlantoaxial instability or 2019 May 23 A retro-odontoid pseudotumor (ROP) is commonly associated with atlantoaxial instability (AAI) or rheumatoid arthritis (RA). However, we describe a patient with ROP in the absence of AAI or RA. An 81-year-old man who did not have a history of trauma to the head and neck admitted with neck pain, right upper extremity numbness, lower limb weakness, and walking disturbance. He had a history of C2 dome and C3-7 laminoplasty 10 years ago. Magnetic resonance imaging revealed a retro-odontoid mass with cervical cord compression. Dynamic radiography did not show signs of AAI. He underwent C1 laminectomy without fixation for the ROP. We speculated that the load on C1 and C2 increased because of the progression of kyphosis from C2 to C7 with increases in range of motion, which in turn caused change in the biomechanics of the cervical spine, leading to recurrent partial tear and degradation of the transverse ligament that induced formation of the ROP. Spinal surgeons should keep this complication in mind and inform patients about this potential postoperative complication.
32173263 Pregnancy and autoimmune diseases. 2020 Apr Autoimmune diseases (AID) are more prevalent in women than in men, and pregnancy-related factors such as hormonal modulation and fetal microchimerism may influence the future risk of maternal AID. For women with AID, optimizing reproductive health requires a continuum of multidisciplinary care that initiates well before the desire for pregnancy is articulated. Family planning is essential so that pregnancy can be timed when disease is stable and to allow for appropriate medication adjustments. When contraception is used, the choice of method needs to take into consideration underlying disease and laboratory features. For females undergoing gonadotoxic therapy, options for preserving ovarian health and fertility warrant consideration, even among those who are not contemplating future pregnancy. Both maternal and fetal outcomes are optimized with multispecialty care as well as close monitoring during pregnancy and the postpartum period and when treatment regimens compatible with pregnancy are maintained to control underlying disease activity.
30827998 Potential Anticancer Activity of Auranofin. 2019 Gold compounds have a long history of use in medicine. Auranofin was developed more than 30 years ago as an oral therapy for rheumatoid arthritis. Now, however, auranofin is rarely used in clinical practice despite its efficacy for treating rheumatoid arthritis because more novel antirheumatic medications are available. Although its use in clinical practice has decreased, studies on auranofin have continued and it shows promise for the treatment of several different diseases, including cancer and bacterial and parasitic infections. Several potential novel applications of auranofin for treating human disease have been proposed. Auranofin inhibits the activity of thioredoxin reductase (TrxR), an enzyme of the thioredoxin (Trx) system that is important for maintaining the intracellular redox state. Particularly in cancers, TrxR inhibition leads to an increase in cellular oxidative stress and induces apoptosis. TrxR overexpression is associated with aggressive tumor progression and poor survival in patients with breast, ovarian, and lung cancers. The Trx system may represent an attractive target for the development of new cancer treatments. Therefore, the TrxR inhibitor auranofin may be a potent anticancer agent. This review summarizes the current understanding of auranofin for cancer therapy.
30721326 Correction to: On-drug and drug-free remission by baseline symptom duration: abatacept wit 2019 May The article "On-drug and drug-free remission by baseline symptom duration: abatacept with methotrexate in patients with early rheumatoid arthritis", written by Vivian P.Bykerk, was originally published Online First without open access.
31258709 Brucine inhibits TNF-α-induced HFLS-RA cell proliferation by activating the JNK signaling 2019 Jul Rheumatoid arthritis (RA) is a diffuse connective tissue disease. Brucine selectively inhibits cell immunity, immune hypersensitivity and induces apoptosis. The current study aimed to investigate effects of brucine on human fibroblast-like synoviocytes (HFLS) of RA and to clarify associated molecular mechanisms. HFLS-RA were treated with tumor necrosis factor (TNF)-α prior to treatment with brucine at carrying concentrations. Cell Counting Kit-8 assays were performed to evaluate HFLS-RA proliferation. Western blot assays were employed to examine c-Jun N-terminal kinase (JNK) expression and phosphorylation in TNF-α-induced HFLS-RA. An association between brucine treatment and JNK phosphorylation was assessed by employing a linear regression analysis. The results suggested that low doses of brucine (0.125 and 0.25 mg/ml) significantly reversed proliferation effects induced by TNF-α, however, final cell viabilities were increased compared with the untreated control (P>0.05 and P<0.05, respectively). High brucine doses (≥0.5 mg/ml) significantly reversed TNF-α-induced proliferation and further inhibited viability compared with the untreated control (P<0.05). Regarding JNK expression, there were no significant differences among the brucine treatment, and between the Control and the TNF-α groups (P>0.05). Brucine treatment significantly decreased JNK phosphorylation compared with the TNF-α group (P<0.05). JNK specific inhibitor, SP600125, significantly inhibited brucine-induced cell viability enhancement compared with the brucine-treated groups without inhibitor (P<0.05). A linear regression analysis suggested that brucine was associated with JNK phosphorylation in TNF-α-treated HFLS-RA. In conclusion, brucine significantly inhibited TNF-α-induced HFLS-RA proliferation by activating the JNK signaling pathway. Therefore, brucine may have potential clinical applications in the treatment of RA.
30847477 Correlation between systemic osteoporosis and local bone erosion with rheumatoid arthritis 2019 Mar 7 OBJECTIVE: RA is a systemic auto-immune inflammatory disease that can lead to local bone erosions and generalized osteoporosis (OP). The aim of this study was to investigate the relationship between systemic osteoporosis and local bone erosion with RA patients in the Chinese population. METHODS: In total, 1235 patients with RA and 158 normal subjects were enrolled in this study. Clinical and laboratory features were recorded in detail. Information about functional class and physical activity was collected using specific questionnaires. Dual-energy X-ray absorptiometry was used to measure BMD. The MECALL castor-50-hf model X-ray scanner was used for two-hand (including wrist) photographs. RESULTS: The median Sharp scores differed significantly between the normal bone mass group, osteopenia group and OP group (P < 0.001). There was a modest negative linear correlation between Sharp and HAQ scores and longer disease duration (P < 0.001). There was a clear increasing trend in Sharp score, incidence of OP and HAQ score in the different DAS in 28 joints (DAS28) activity groups (P < 0.001). Spearman's correlation test showed that Sharp and HAQ scores were negatively correlated with BMD at all measured sites (femoral neck, total hip and L1-4) (P < 0.001). Logistic regression indicated that age, female gender, and Sharp and HAQ scores were independent risk factors in the occurrence of OP in RA patients. The use of DMARDs and BMI were protective factors for OP. CONCLUSION: These results suggest that BMD is associated with local bone erosion among Chinese patients with RA. Local bone erosion is closely related to clinical symptoms and BMD in patients with RA.
31695611 Comparison of Healthcare Utilization and Costs Between RA Patients Receiving Biological an 2019 Background: The therapy with biological disease-modifying anti-rheumatic drugs (bDMARDs) has proven to rapidly reduce articular symptoms/signs, decrease morbidities, and improve health outcome in patients with rheumatoid arthritis (RA) and be cost-effective in Western countries. However, the difference in healthcare utilization and costs between conventional synthetic DMARDs (csDMARDs) and bDMARDs in the treatment of RA patients in Taiwan remains largely unexplored. Methods: Two cohorts of RA patients and their matched controls were identified from the National Health Insurance Research database (NHIRD). The csDMARD cohort comprised of patients who submitted claims during 1997-2003 for cyclosporine≥50 mg/day with concomitant use of ≥2 csDMARDs for ≥28 days (n=1,569), whilst the bDMARD cohort comprised of patients who had ≥1 claim during 2003-2011 for bDMARD (n = 1,530). The per-patient per-year healthcare utilization and costs were estimated by bootstrapping method, with a comparison being undertaken between csDMARD and bDMARD. Results: The incremental number of hospitalization days was reduced from 2.3 days for csDMARD to 0.58 day for bDMARD. When compared to csDMARD-treated patients, the incremental total costs and RA-related medication costs were significantly higher in bDMARD-treated patients (US$9,081 vs. US$2,481; US$8,992 vs. US$1,883). However, the combined incremental healthcare utilization costs and non-RA medication costs were significantly lower in bDMARDs-treated patients compared to csDMARD-treated patients (US$374.7 vs. US$1,156.2). Conclusion: Although total costs increased as a result of introducing biologics in RA treatment, biologics have undoubtedly given rise to the benefits of reduced healthcare utilization. The increase in medication costs from biologics was offset by the lower costs of healthcare utilization. Our findings suggest that the medication costs of biologics may be alleviated by an improvement in clinical outcomes.
31620119 Interactome of the Autoimmune Risk Protein ANKRD55. 2019 The ankyrin repeat domain-55 (ANKRD55) gene contains intronic single nucleotide polymorphisms (SNPs) associated with risk to contract multiple sclerosis, rheumatoid arthritis or other autoimmune disorders. Risk alleles of these SNPs are associated with higher levels of ANKRD55 in CD4(+) T cells. The biological function of ANKRD55 is unknown, but given that ankyrin repeat domains constitute one of the most common protein-protein interaction platforms in nature, it is likely to function in complex with other proteins. Thus, identification of its protein interactomes may provide clues. We identified ANKRD55 interactomes via recombinant overexpression in HEK293 or HeLa cells and mass spectrometry. One hundred forty-eight specifically interacting proteins were found in total protein extracts and 22 in extracts of sucrose gradient-purified nuclei. Bioinformatic analysis suggested that the ANKRD55-protein partners from total protein extracts were related to nucleotide and ATP binding, enriched in nuclear transport terms and associated with cell cycle and RNA, lipid and amino acid metabolism. The enrichment analysis of the ANKRD55-protein partners from nuclear extracts is related to sumoylation, RNA binding, processes associated with cell cycle, RNA transport, nucleotide and ATP binding. The interaction between overexpressed ANKRD55 isoform 001 and endogenous RPS3, the cohesins SMC1A and SMC3, CLTC, PRKDC, VIM, β-tubulin isoforms, and 14-3-3 isoforms were validated by western blot, reverse immunoprecipitaton and/or confocal microscopy. We also identified three phosphorylation sites in ANKRD55, with S436 exhibiting the highest score as likely 14-3-3 binding phosphosite. Our study suggests that ANKRD55 may exert function(s) in the formation or architecture of multiple protein complexes, and is regulated by (de)phosphorylation reactions. Based on interactome and subcellular localization analysis, ANKRD55 is likely transported into the nucleus by the classical nuclear import pathway and is involved in mitosis, probably via effects associated with mitotic spindle dynamics.