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ID PMID Title PublicationDate abstract
35292759 Nesfatin-1 exerts protective effects on acidosis-stimulated chondrocytes and rats with adj 2022 Mar 15 Nesfatin-1, a newly identified energy-regulating peptide, has been reported to possess antioxidant, anti-inflammatory, and antiapoptotic properties; however, to date, its effect on rheumatoid arthritis (RA) has not been previously explored in detail. We previously showed that activation of acid-sensing ion channel 1a (ASIC1a) by acidosis plays an important role in RA pathogenesis. Therefore, in this study, we evaluated the effects of nesfatin-1 on acidosis-stimulated chondrocyte injury in vitro and in vivo and examined the involvement of ASIC1a and the mechanism underlying the effects of nesfatin-1 on RA. Acid-stimulated articular chondrocytes were used to examine one of the several possible mechanisms underlying RA pathogenesis in vitro. The mRNA expression profile of acid-induced chondrocytes treated or not treated with nesfatin-1 was investigated by RNA sequencing. The effects of nesfatin-1 on oxidative stress, inflammation, and apoptosis in acid-induced chondrocytes were measured. The mechanistic effect of nesfatin-1 on ASIC1a expression and intracellular Ca(2+) in acid-stimulated chondrocytes was studied. Rats with adjuvant-induced arthritis (AA) were used for in vivo analysis of RA pathophysiology. Cartilage degradation and ASIC1a expression in chondrocytes were detected in rats with AA after intraarticular nesfatin-1 injection. The in vitro experiments showed that nesfatin-1 decreased acidosis-induced cytotoxicity and elevation of intracellular Ca(2+) levels in chondrocytes. Moreover, it attenuated acid-induced oxidative stress, inflammation, and apoptosis in chondrocytes. Nesfatin-1 decreased ASIC1a protein levels in acid-stimulated chondrocytes via the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) and nuclear factor kappa-B (NF-κB) signaling pathways. In vivo analysis showed that nesfatin-1 ameliorated cartilage degradation and decreased ASIC1a expression in the chondrocytes of rats with AA. Collectively, nesfatin-1 suppressed acidosis-induced oxidative stress, inflammation, and apoptosis in acid-stimulated chondrocytes and alleviated arthritis symptoms in rats with AA, and its mechanism may be related to its ability to decrease ASIC1a protein levels via the MAPK/ERK and NF-κB pathways.
35228792 Dry Eye Disease Symptoms and Its Association with Daily Beverage Intake Among Adults in Sa 2022 PURPOSE: To evaluate the association between dry eye disease (DED) symptoms and daily beverage intake among adults in Saudi Arabia. PATIENTS AND METHODS: In this cross-sectional, questionnaire-based study, we distributed an online questionnaire to men and women older than 18 years living in Saudi Arabia. The questionnaire consisted of items related to the sociodemographic characteristics of the participants and two validated indices: the Ocular Surface Disease Index (OSDI) and the brief 15-item Beverage Intake Questionnaire (BEVQ-15). Participants were excluded if they were aged less than 18 years; wore contact lenses; had existing eye disease (excluding refractive errors), history of eye surgery (including corrective eye surgeries), or autoimmune diseases (rheumatoid arthritis, systemic lupus erythematosus, Sjogren's syndrome); or were currently taking specific medications including antidepressants, antihistamines, and diuretics. RESULTS: After applying the study exclusion criteria, a total of 615 participants were included in the statistical analysis. The majority of participants were 18-34 years old (450, 73.2%), and men (381, 62%) exceeded women (234, 38%) by approximately 1.5-fold. OSDI scores showed that 344 participants (55.9%) had DED symptoms, 145 (23.6%) had mild dry eyes; and 106 (17.2%) and 93 (15.1%) had moderate and severe dry eyes, respectively. There was a significant association between sex and DED symptoms (p = 0.012); the frequency of DED symptoms in women exceeded that in men. However, no significant differences were observed with other demographic data such as age and location of residence. Although beverage intake was moderately correlated to OSDI score (R = 0.27), we found no significant association between beverage intake and DED symptoms. CONCLUSION: This is the first study to highlight the association between DED symptoms and daily beverage intake. We found a significant association between DED symptoms and female sex. However, no significant association was found between DED symptoms and other demographic characteristics or beverage intake.
35378227 Repurposing Non-Antibiotic Drugs Auranofin and Pentamidine in Combination to Combat Multid 2022 May OBJECTIVES: Infections caused by multidrug-resistant (MDR) bacteria, especially MDR Gram-negative bacteria, have posed a great challenge to healthcare systems globally. To address the shortage of effective antibiotics against MDR Gram-negative bacterial infections, two non-antibiotic drugs - auranofin (rheumatoid arthritis drug) and pentamidine (antiprotozoal drug) - are being repurposed to treat MDR Gram-negative bacteria by a combination approach. METHODS: Chequerboard microdilution assay was used to determine the interaction of auranofin and pentamidine against drug-susceptible and MDR Gram-negative bacteria (Escherichia coli, Acinetobacter baumannii and Klebsiella pneumoniae). Fluorescence microscopy, scanning electron microscopy and inductively coupled plasma mass spectrometry were used to explore the mechanism of synergistic antibacterial effect. RESULTS: These two non-antibiotic drugs displayed a strong synergistic antibacterial effect, with the fraction inhibitory concentration index ranging 0.094-0.506. The MIC of auranofin reduced by as much as ≥ 1024-fold when combined with pentamidine at sub-MIC. Fluorescence and inductively coupled plasma mass spectrometry analyses revealed that bacterial membrane disruption caused by pentamidine treatment at sub-MIC led to an increased intracellular auranofin content with the combination treatment. The enhanced auranofin uptake in bacteria resulted in efficient bacterial killing. More importantly, the auranofin/pentamidine combination slowed down auranofin resistance development in clinically isolated MDR bacteria (Klebsiella pneumoniae) more than the combination of auranofin and colistin, which is a last-line antibiotic with a membrane-lytic antibacterial mechanism. CONCLUSION: The combination of non-antibiotic drugs with complementary antibacterial mechanisms provides a potentially promising approach to discover new antibacterial drugs and delay drug resistance development.
35179251 Fostamatinib for the treatment of warm antibody autoimmune hemolytic anemia: Phase 2, mult 2022 Jun 1 Patients with relapsed warm antibody autoimmune hemolytic anemia (wAIHA) have limited treatment options. Fostamatinib is a potent, orally administered spleen tyrosine kinase inhibitor approved in the United States and Europe for the treatment of adults with chronic immune thrombocytopenia (ITP). This phase 2 study evaluated the response to fostamatinib, administered at 150 mg BID orally with or without food in adults with wAIHA and active hemolysis with hemoglobin (Hgb) <10 g/dL who had failed at least one prior treatment. Hemoglobin levels and safety assessments were performed at visits every 2 weeks. The primary endpoint was Hgb >10 g/dL with an increase of ≥2 g/dL from baseline by week 24 without rescue therapy or red blood cell transfusion. Eleven of 24 (46%) patients achieved the primary endpoint. Increases in median Hgb were detected at week 2 and sustained over time. Median lactate dehydrogenase levels and reticulocyte counts generally declined over time with little change in median haptoglobin levels. The most common adverse events (AEs) were diarrhea (42%), fatigue (42%), hypertension (27%), dizziness (27%), and insomnia (23%). AEs were manageable and consistent with the fostamatinib safety database of over 3900 patients across multiple diseases (rheumatoid arthritis, B-cell lymphoma, COVID-19, and ITP). No new safety signals were detected. Fostamatinib may be a promising therapeutic option for wAIHA. A randomized, double-blind, phase 3 study is nearing completion.
35432384 Small RNA Expression Profiling Reveals hsa-miR-181d-5p Downregulation Associated With TNF- 2022 MicroRNAs (miRNAs) are small non-coding RNAs (sRNA), that alter gene expression by binding to target messenger RNAs (mRNAs) and repressing translation. Dysregulated miRNA expression has been implicated in the pathogenesis of autoimmune diseases such as Sjögren's syndrome (SS). The aim of this study was to characterize the global profile of sRNAs in labial salivary glands (LSG) from SS-patients and to validate potential miRNA candidates implicated in glandular inflammation. LSG from 21 SS-patients and 9 sicca controls were analyzed. A global next generation sequencing (NGS)-based sRNA profiling approach was employed to identify direct targets whereby differentially expressed miRNAs were predicted using bioinformatics tools. miRNA levels were validated by TaqMan and target mRNA levels were determined by quantitative real-time PCR. We also performed in vitro assays using recombinant TNF-α. NGS shows that ~30% of sRNAs were miRNAs. In comparison with samples from sicca controls, four miRNAs were found differentially expressed in LSG from SS-patients with low focus score (LFS) and 18 from SS-patients with high focus score (HFS). The miRNA with the most significant changes identified by NGS was hsa-miR-181d-5p and downregulation was confirmed by TaqMan analysis. Levels of TNF-α mRNA, a direct target of hsa-miR-181d-5p, were significantly increased and negatively correlated with hsa-miR-181d-5p presence. Moreover, positive correlations between TNF-α transcript levels, focus score, ESSDAI, and autoantibody levels were also detected. Furthermore, TNF-α stimulation decreased hsa-miR-181d-5p levels in vitro. Downregulation of hsa-miR-181d-5p in LSG from SS-patients could contribute to the glandular pro-inflammatory environment by deregulation of its direct target TNF-α. Further dissection of the pathophysiological mechanisms underlying the hsa-miR-181d-5p-mediated action in inflammatory conditions could be useful to evaluate the benefits of increasing hsa-miR-181d-5p levels for restoration of salivary gland epithelial cell architecture and function.
35414631 Immunogenicity and safety of COVID-19 vaccination in patients with primary Sjögren's synd 2022 Apr OBJECTIVES: To evaluate humoral and cellular immune responses and adverse events (AEs) after COVID-19 vaccination in patients with primary Sjögren's syndrome (pSS) compared to healthy controls (HC), and disease activity following vaccination in patients with pSS. METHODS: 67 patients with pSS and 33 HC (ratio 2:1) received COVID-19 vaccinations following the Dutch vaccination programme. Patients with pSS did not use immunomodulatory drugs, except hydroxychloroquine. Anti-spike 1 receptor binding domain IgG serum antibody levels were measured 28 days after complete vaccination. AEs were collected 7 days after vaccination. In a subgroup, salivary anti-SARS-CoV-2 antibodies and T-cell response by interferon-γ enzyme-linked immune absorbent spot was measured. RESULTS: 47 patients with pSS (70%) and 14 HC (42%) received BNT162b2 (Pfizer-BioNtech), 13 (19%) and 5 (15%) received ChAdOx1 nCoV-19 (AstraZeneca), 6 (9%) and 8 (24%) received mRNA-1273 (Moderna), and 1 (1%) and 6 (18%) received Ad.26.COV2.S (Janssen). All participants had positive anti-SARS-CoV-2 antibody levels (>2500 AU/mL) postvaccination. No differences in anti-SARS-CoV-2 antibody levels were observed between patients with pSS and HC, for each vaccine type. Salivary anti-SARS-CoV-2 IgG antibodies also increased, and a T-cell response was observed in patients with pSS and HC. Frequencies of systemic AEs were comparable between patients with pSS and HC (first vaccination: 34/67 (51%) vs 16/33 (48%), p=0.83; second: 41/66 (62%) vs 14/25 (56%), p=0.59). No significant worsening was observed in patient-reported and systemic disease activity, including auto-antibodies. CONCLUSIONS: Patients with pSS had similar humoral and cellular immune responses as HC, suggesting COVID-19 vaccination is effective in patients with pSS. AEs were also comparable, and no increase in disease activity was seen in patients with pSS.
34334359 Screening for Hepatitis B Virus Prior to Initiating Tocilizumab and Tofacitinib in Patient 2022 Jan OBJECTIVE: Hepatitis B virus (HBV) can reactivate among rheumatology patients initiating tocilizumab (TCZ) or tofacitinib (TOF). HBV screening is recommended by the Centers for Disease Control and Prevention (CDC), the American Association for the Study of Liver Diseases (AASLD), and the Canadian Rheumatology Association, but it is not explicitly recommended by the American College of Rheumatology. METHODS: We conducted a cross-sectional study to characterize HBV screening practices for adult rheumatology patients initiating TCZ or TOF before December 31, 2018, in the Greater Boston area. We classified appropriate HBV screening patterns prior to TCZ or TOF (i.e., HBV surface antigen [HBsAg], total core antibody [anti-HBcAb], and surface antibody [HBsAb]) as follows: complete (all 3 tested), partial (any 1 or 2 tests), or none. We determined the frequency of inappropriate HBV testing (HBV e-antigen, anti-HBcAb IgM, or HBV DNA without a positive HBsAg or total anti-HBcAb) and used multivariable regression to assess factors associated with complete HBV screening. RESULTS: Among 678 subjects initiating TCZ, 194 (29%) completed appropriate HBV screening, 307 (45%) had partial screening, and 177 (26%) had none. Among 391 subjects initiating TOF, 94 (24%) completed appropriate HBV screening, 195 (50%) had partial screening, and 102 (26%) had none. Inappropriate testing was performed in 22% of subjects. Race was associated with complete HBV screening (White vs non-White: OR 0.74, 95% CI 0.57-0.95), whereas prior immunosuppression was not (conventional synthetic disease-modifying antirheumatic drugs [DMARDs]: OR 1.05, 95% CI 0.72-1.55; biologic DMARDs: OR 0.73, 95% CI 0.48-1.12). CONCLUSION: Patients initiating TCZ or TOF are infrequently screened for HBV despite recommendations from the AASLD and CDC.
35617780 DMARD disruption, rheumatic disease flare, and prolonged COVID-19 symptom duration after a 2022 May 18 OBJECTIVE: To describe disease-modifying antirheumatic drug (DMARD) disruption, rheumatic disease flare/activity, and prolonged COVID-19 symptom duration among COVID-19 survivors with systemic autoimmune rheumatic diseases (SARDs). METHODS: We surveyed people with pre-existing SARDs who had confirmed COVID-19 at Mass General Brigham to investigate post-acute sequelae of COVID-19. We obtained data on demographics, clinical characteristics, COVID-19 symptoms/course, and patient-reported measures. We examined baseline predictors of prolonged COVID-19 symptom duration (defined as lasting ≥28 days) using logistic regression. RESULTS: We analyzed surveys from 174 COVID-19 survivors (mean age 52 years, 81% female, 80% White, 50% rheumatoid arthritis) between March 2021 and January 2022. Fifty-one percent of 127 respondents on any DMARD reported a disruption to their regimen after COVID-19 onset. For individual DMARDs, 56-77% had any change, except for hydroxychloroquine (23%) and rituximab (46%). SARD flare after COVID-19 was reported by 41%. Global patient-reported disease activity was worse at the time of survey than before COVID-19 (mean 6.6±2.9 vs. 7.6±2.3, p<0.001). Median time to COVID-19 symptom resolution was 25 days (IQR 11, 160). Prolonged symptom duration of ≥28 days occurred in 45%. Hospitalization for COVID-19 (OR 3.54, 95%CI 1.27-9.87) and initial COVID-19 symptom count (OR 1.38 per symptom, 95%CI 1.17-1.63) were associated with prolonged symptom duration. Respondents experiencing prolonged symptom duration had higher RAPID3 scores (p=0.007) and more pain (p<0.001) and fatigue (p=0.03) compared to those without prolonged symptoms. CONCLUSION: DMARD disruption, SARD flare, and prolonged COVID-19 symptom duration were common in this prospective study of COVID-19 survivors, suggesting substantial impact on SARDs after acute COVID-19.
34662086 Biosimilars Use In Medicine For Inflammatory Diseases. 2022 Jan Biosimilars are biological agents that are highly analogous to their reference products currently approved and licensed by the U.S. Food and Drug Administration (FDA). Biosimilars possess no differences in their safety, purity, potency, or effectiveness compared to their respective reference biologic agents. The abbreviated licensure pathway 351(k) for biosimilars or agents interchangeable with FDA-approved biological agents (reference product) was formed by Congress by The Biologics Price Competition and Innovation Act (BPCI Act) of 2009. Biosimilars aim to increase the number of biologics available at more inexpensive costs when compared to their reference products, further increasing patient access to more treatment options. Similar to biologics or reference products, biosimilars are expected to meet the FDA's meticulous approval criteria, ensuring the reliability of the agent's safety, efficacy, quality, and effectiveness. The FDA approval process for biosimilars is based on data proving its prominent similarity and correlation to an already FDA-approved biologic agent (reference product) and its indications for use. No clinically meaningful differences among the biosimilar and its respective reference agent should exist. Differences exist in the regulatory provisions for the original biologic agent (reference product) and a biosimilar as the biosimilars obtain approval from FDA by their abbreviated approval pathway. Biosimilars seeking FDA approval must include data assessments demonstrating the agent's similarity to a reference product acquired from analytical investigations, animal studies, and clinical studies. Added data and analyses of the biosimilars immunogenicity, pharmacokinetics, pharmacodynamics, and data discussing the indication(s) the reference product is licensed and approved for use are also included. To date, ten biological agents: bevacizumab, etanercept, epoetin-alfa, trastuzumab, adalimumab, pegfilgrastim, filgrastim, infliximab, rituximab, and insulin glargine, have been used as reference products for the approval of 30 biosimilar agents. Biosimilars can be used in the management of various inflammatory and autoimmune diseases. Ailments such as rheumatoid arthritis (RA), polyarticular juvenile idiopathic arthritis (JIA), psoriatic arthritis (PA), ankylosing spondylitis (AS), plaque psoriasis (PsO), inflammatory bowel disease (IBD): adult Crohn disease (CD), ulcerative colitis (UC), granulomatosis with polyangiitis (GPA) (Wegener granulomatosis), microscopic polyangiitis (MPA), and type 1 diabetes mellitus (DM). Filgrastim-sndz, a biosimilar of the reference product "filgrastim," was the first-ever biosimilar to receive FDA approval in March 2015 and is characterized as a leukocyte growth factor indicated to reduce infections caused by febrile neutropenia in the neutropenic and immunosuppressed subjects. Other indications of biosimilars alongside inflammatory diseases include management for specific malignancies and secondary causes of anemia. In September 2017, bevacizumab-awwb was the first biosimilar that was granted FDA approval for certain cancers. A few months later, in December 2017, biosimilar trastuzumab-dkst was also granted FDA approval for specific malignancies. Cancers indicative of biosimilar therapy include non-squamous non-small cell lung cancer, metastatic colorectal cancer, metastatic renal cell carcinoma, glioblastoma, recurrent or metastatic cervical cancer, HER2 (human epidermal growth factor receptor 2) associated breast cancer, and HER2 associated gastric (metastatic) or gastroesophageal junction adenocarcinoma, chronic lymphocytic leukemia (CLL), non-Hodgkin lymphoma (NHL). To date, new biosimilars are currently still being FDA approved, with the latest approval coming on July 28, 2021, for biosimilar agent insulin glargine-yfgn, a long-acting insulin agent indicated for pediatric type 1 diabetes mellitus (DM) and adult patients with DM type 1 and DM type 2. Biosimilars agent insulin glargine-yfgn is the first insulin biosimilar agent to receive FDA approval and is also the first interchangeable agent in the class of biosimilar agents. Interchangeable products are biosimilars that meet additional criteria specified by the Biologics Price Competition and Innovation Act during the assessment and testing of the agent during its FDA approval process. Data is required demonstrating clinical results as its respective reference product in any subject treated with the interchangeable products. Data on the interchangeable products substituted with their reference product in terms of safety and efficacy of alternating back and forth have been assessed and evaluated by the FDA prior to their approval. Once an interchangeable product has been approved, it may be interchanged for their reference product without requiring additional consulting from the prescribing clinician or healthcare professional. Table 1: Summarizes all FDA approved biosimilars
35470158 Multiomics analysis of rheumatoid arthritis yields sequence variants that have large effec 2022 Apr 25 OBJECTIVES: To find causal genes for rheumatoid arthritis (RA) and its seropositive (RF and/or ACPA positive) and seronegative subsets. METHODS: We performed a genome-wide association study (GWAS) of 31 313 RA cases (68% seropositive) and ~1 million controls from Northwestern Europe. We searched for causal genes outside the HLA-locus through effect on coding, mRNA expression in several tissues and/or levels of plasma proteins (SomaScan) and did network analysis (Qiagen). RESULTS: We found 25 sequence variants for RA overall, 33 for seropositive and 2 for seronegative RA, altogether 37 sequence variants at 34 non-HLA loci, of which 15 are novel. Genomic, transcriptomic and proteomic analysis of these yielded 25 causal genes in seropositive RA and additional two overall. Most encode proteins in the network of interferon-alpha/beta and IL-12/23 that signal through the JAK/STAT-pathway. Highlighting those with largest effect on seropositive RA, a rare missense variant in STAT4 (rs140675301-A) that is independent of reported non-coding STAT4-variants, increases the risk of seropositive RA 2.27-fold (p=2.1×10(-9)), more than the rs2476601-A missense variant in PTPN22 (OR=1.59, p=1.3×10(-160)). STAT4 rs140675301-A replaces hydrophilic glutamic acid with hydrophobic valine (Glu128Val) in a conserved, surface-exposed loop. A stop-mutation (rs76428106-C) in FLT3 increases seropositive RA risk (OR=1.35, p=6.6×10(-11)). Independent missense variants in TYK2 (rs34536443-C, rs12720356-C, rs35018800-A, latter two novel) associate with decreased risk of seropositive RA (ORs=0.63-0.87, p=10(-9)-10(-27)) and decreased plasma levels of interferon-alpha/beta receptor 1 that signals through TYK2/JAK1/STAT4. CONCLUSION: Sequence variants pointing to causal genes in the JAK/STAT pathway have largest effect on seropositive RA, while associations with seronegative RA remain scarce.
35570628 [Short-term effectiveness of MAKO robot assisted complex total hip arthroplasty]. 2022 May 15 OBJECTIVE: To investigate the short-term effectiveness of MAKO robot assisted complex total hip arthroplasty (THA). METHODS: The clinical data of 15 patients (17 hips) underwent MAKO robot assisted complex THA between May 2020 and June 2021 were analyzed retrospectively. There were 5 males and 10 females with the age ranged from 19 to 70 years (median, 49 years), included 9 cases (9 hips) of developmental dysplasia of the hip (Crowe type â…¡ in 5 hips, type â…¢ in 1 hip, and type â…£ in 3 hips), 1 case (2 hips) of rheumatoid arthritis, 2 cases (3 hips) of ankylosing spondylitis, 3 cases (3 hips) of secondary arthritis with a history of acetabular fracture and internal fixation. The acetabular cup abduction angle and anteversion angle were measured at 3 months after operation, and compared with those measured by MAKO robot system before and immediately after operation. The femoral offset and leg length discrepancy (LLD) were measured at 3 months after operation, which were compared with those before operation. Harris hip score (HHS) and visual analogue scale (VAS) score were used to evaluate hip function before operation and at 3 months after operation. RESULTS: All 15 patients (17 hips) completed the operation successfully. The operation time was 75-175 minutes, with an average of 116.3 minutes; the intraoperative blood loss was 100-800 mL, with an average of 381.3 mL. Two patients were not included in the statistics because of intraoperative and postoperative complications, the remaining 13 patients (15 hips) had no serious complication such as vascular and nerve injuries, and 3 patients had intermuscular vein thrombosis. The 13 patients (15 hips) were followed up 3-15 months, with an average of 8 months. At last follow-up, the position of prosthesis did not change and there was no signs of loosening. There was no significant difference in acetabular abduction angle at immediate and 3 months after operation when compared with preoperative one ( P>0.05), and the acetabular anteversion angle was significantly lower than that before operation ( P<0.05). There was no significant difference in acetabular abduction angle and anteversion angle between at immediate and 3 months after operation ( P>0.05). The LLD, offset, HHS score, and VAS score were significantly improved at 3 months after operation when compared with preoperative ones ( P<0.05). CONCLUSION: MAKO robot assisted complex THA can achieve good short-term effectiveness, improve the hip range of motion, reduce the length difference between bilateral lower limbs, and improve the quality of patients' life.
35168627 CD34(+)THY1(+) synovial fibroblast subset in arthritic joints has high osteoblastic and ch 2022 Feb 15 OBJECTIVE: Synovial fibroblasts (SFs) in rheumatoid arthritis (RA) and osteoarthritis (OA) play biphasic roles in joint destruction and regeneration of bone/cartilage as mesenchymal stem cells (MSCs). Although MSCs contribute to joint homeostasis, such function is impaired in arthritic joints. We have identified functionally distinct three SF subsets characterized by the expression of CD34 and THY1 as follows: CD34(+)THY1(+), CD34(-)THY1(-), and CD34(-)THY1(+). The objective of this study was to clarify the differentiation potentials as MSCs in each SF subset since both molecules would be associated with the MSC function. METHODS: SF subsets were isolated from synovial tissues of 70 patients (RA: 18, OA: 52). Expressions of surface markers associated with MSCs (THY1, CD34, CD73, CD271, CD54, CD44, and CD29) were evaluated in fleshly isolated SF subsets by flow cytometry. The differentiation potentials of osteogenesis, chondrogenesis, and adipogenesis were evaluated with histological staining and a quantitative polymerase chain reaction of differentiation marker genes. Small interfering RNA was examined to deplete THY1 in SFs. RESULTS: The expression levels of THY1(+), CD73(+), and CD271(+) were highest and those of CD54(+) and CD29(+) were lowest in CD34(+)THY1(+) among three subsets. Comparing three subsets, the calcified area, alkaline phosphatase (ALP)-stained area, and cartilage matrix subset were the largest in the CD34(+)THY1(+) subset. Consistently, the expressions of differentiation markers of the osteoblasts (RUNX2, ALPL, and OCN) or chondrocytes (ACAN) were the highest in the CD34(+)THY1(+) subset, indicating that the CD34(+)THY1(+) subset possessed the highest osteogenic and chondrogenic potential among three subsets, while the differentiation potentials to adipocytes were comparable among the subsets regarding lipid droplet formations and the expression of LPL and PPARγ. The knockdown of THY1 in bulk SFs resulted in impaired osteoblast differentiation indicating some functional aspects in this stem-cell marker. CONCLUSION: The CD34(+)THY1(+) SF subset has high osteogenic and chondrogenic potentials. The preferential enhancement of MSC functions in the CD34(+)THY1(+) subset may provide a new treatment strategy for regenerating damaged bone/cartilage in arthritic joints.
35049423 Antibody response in patients with autoimmune inflammatory rheumatic disease after pneumoc 2022 Jan 20 OBJECTIVE: The aim of the study was to assess the pneumococcal antibody response in autoimmune inflammatory rheumatic disease (AIIRD) patients receiving 23-valent pneumococcal polysaccharide vaccine (PPV23) as a prime vaccination or revaccination. METHOD: Antibodies to 12 serotypes occurring in the commonly applied pneumococcal vaccines in Denmark were measured in AIIRD patients receiving biological disease-modifying anti-rheumatic drug (bDMARD) treatment for rheumatoid arthritis, spondyloarthritis, or psoriatic arthritis. Patients with a non-protective level of pneumococcal antibodies (geometric mean pneumococcal antibody level < 1 μg/mL) were invited to receive vaccination with PPV23 followed by control of antibody titre 3 months later. RESULTS: In total, 224 (74%) of 301 patients were included in the analyses, of whom 126 patients had previously received PPV23 vaccination. Post-vaccination antibody measurement revealed that only 80 patients (36%) achieved a protective level of antibodies. In a multivariable logistic regression analysis, significantly more patients without a previous PPV23 vaccination history achieved a protective antibody level compared with patients with a history of PPV23 vaccination less than 5 years ago (p = 0.005). This difference was not seen when comparing the former group with patients vaccinated 5 years ago or more. Methotrexate (MTX) treatment at the time of vaccination was associated with a non-protective antibody level (p < 0.001). CONCLUSION: Only 36% of patients with a non-protective antibody level achieved a protective level in response to pneumococcal vaccination. Pneumococcal vaccination within the last 5 years and MTX treatment at the time of vaccination were independently associated with a poor antibody response.
35438147 Exploring discordance between Health Literacy Questionnaire scores of people with RMDs and 2022 Apr 19 OBJECTIVES: We studied discordance between health literacy of people with rheumatic and musculoskeletal diseases (RMDs) and assessment of health literacy by their treating health professionals, and explored whether discordance is associated with the patients' socioeconomic background. METHODS: Patients with rheumatoid arthritis (RA), spondyloarthritis (SpA), or gout from three Dutch outpatient rheumatology clinics completed the nine-domain Health Literacy Questionnaire (HLQ). Treating health professionals assessed their patients on each HLQ domain. Discordance per domain was defined as a ≥ 2-point difference on a 0-10 scale (except if both scores were below three or above seven), leading to three categories: "negative discordance" (i.e. professional scored lower), "probably the same", or "positive discordance" (i.e. professional scored higher). We used multivariable multilevel multinomial regression models with patients clustered by health professionals to test associations with socioeconomic factors (age, gender, education level, migration background, employment, disability for work, living alone). RESULTS: We observed considerable discordance (21-40% of patients) across HLQ domains. Most discordance occurred for "Critically appraising information" (40.5%, domain 5). Comparatively, positive discordance occurred more frequently. Negative discordance was more frequently and strongly associated with socioeconomic factors, specifically lower education level and non-Western migration background (for five HLQ domains). Associations between socioeconomic factors and positive discordance were less consistent. CONCLUSION: Frequent discordance between patients' scores and professionals' estimations indicates there may be hidden challenges in communication and care, which differ between socioeconomic groups. Successfully addressing patients' health literacy needs cannot solely depend on health professionals' estimations but will require measurement and dialogue.
35406158 Therapeutic Effect of Nile Tilapia Type II Collagen on Rigidity in CD8(+) Cells by Allevia 2022 Mar 22 Fibrillins are microfibril-associated macro glycoproteins found in connective tissues and structurally related to latent TGF-β-binding proteins (LTBPs). The special cellular immunity and blocking glycoprotein receptors IIb and IIIa of fibrillins are emerging topics in recent years. In this study, Nile Tilapia type IIcollagen (NTCII) was extracted and purified from the skull cartilages by a pepsin-soluble method. Amino acid analysis indicated that NTCII consisted of 315/1000 glycine residues, 72/1000 hydroxyproline residues and 108/1000 proline residues. SDS-PAGE analysis showed that NTCII was composed of three identical 130 kDa α-chains. The results of glycoprotein/carbohydrate assay indicated that the total polysaccharide content of NTCII was 5.6-19.0%. The IR spectrum of NTCII displayed five characteristic peaks of amide I, II, III, A, B. NTCII at 10-100 μg/mL concentration downregulated the content of cytokines in the presence or absence of LPS, especially the secretion of cytokines IL-6, IL-1β and TNF-α. Interestingly, NTCII promoted the secretion of Fas/Apo-1 compared to the control group and 25 μg/mL of NTCII resulted in a higher Fas/Apo-1 secretion level in CD8(+) T cells. FITC-TCII fluorescence images confirmed that NTCII could bind to the membrane surface of CD8(+) T cells, leading to the induction of rigidity. NTCII could bind to the membrane surface of CD8(+) T cells that leads to the induction of rigidity, as evidenced by the FITC-NTCII fluorescence images. The qRT-PCR gene expression analysis of caspase-8 collected with Fas/Apo-1 was upregulated significantly in the 1 and 50 μg/mL NTCII-treated groups compared with the control group. Overall, the results conclude that the rigidity did not lead to an increase in inflammatory factors in CD8(+) T cells treated with NTCII. The oral administration of NTCII 3 mg/kg dosage caused more prominent repair of damaged ankle cartilage than the 1 mg/kg dosage in Freund's adjuvant-induced model of arthritis in rats. Therefore, this study disclosed the immunological and anti-arthritic effect of fibrillar collagen, which could be a potential biomaterial for practical applications with lower toxicity.
35129653 Evolution of total hip arthroplasty in patients younger than 30 years of age: A systematic 2022 Feb 7 INTRODUCTION: While surgical technique and implant technology for total hip arthroplasty (THA) has improved over the years, it is unclear whether recent progress has translated to improved clinical outcomes for young patients. The goal of this study is to determine trends in (1) indications, (2) surgical technique (3) clinical and radiographic outcomes, and (4) survivorship for THA in patients younger than 30 years of age. METHODS: MedLine, Cochrane, EMBASE, and Google Scholar were searched using several key phrases for articles focusing on THA performed on patients younger than 30 years of age between 1971 and 2020. A total of 34 qualifying articles were identified and stratified into three groups according to operative years and compared to one another on the basis of (1) indications; (2) fixation technique; (3) implant design; (4) clinical and radiographic outcomes; and (7) survivorship. RESULTS: The mean patient age at index THA were 20.5 (9-30), 22.1 (11-30) and 21.5 (10-30) years, respectively, for each study group. Over time, patients underwent fewer THAs for JRA (Juvenile Rheumatoid Arthritis) (p < 0.001) but more for post-treatment and iatrogenic avascular necrosis (p < 0.001; p < 0.001). Early THAs primarily used metal on UHMWPE (Ultra high molecular weight polyethylene) (71.7%, p < 0.001), modern THA predominantly use ceramic on HXLPE (Highly cross-linked polyethylene) (42.5%, p < 0.001). Early fixation methods used cement (60.4%, p < 0.001), and modern fixation primarily use press fit technology (95.9%, p < 0.001). Prevalence of radiographic loosening decreased significantly (p < 0.001) over time. There was no significant difference in clinical improvement on HHS. Lastly, fewer patients required THA revision in recent decades (p < 0.001). CONCLUSIONS: Advances in surgical technique and technology have served to improve implant longevity. Surprisingly, subjective clinical scores showed no significant improvement over time, suggesting that early iterations of THA were extremely successful.
35428715 Dr. Gunderson et al reply. 2022 Apr 15 We thank Drs. Liao, Liao, and Liaw for their interest in our article on multimorbidity burden in patients with rheumatoid arthritis (RA).(1) We agree that not all morbidities were included in the assessment of multimorbidity in our article, and further research is warranted to more comprehensively assess multimorbidity in patients with RA.
35378210 Identification of potential biomarkers of gout through competitive endogenous RNA network 2022 Jun 1 OBJECTIVE: Gout is a widespread inflammatory arthritis. The present study aimed to identify potential biomarkers of gout and explore their underlying mechanisms through bioinformatics methods. METHODS: The microarray data was downloaded from the GSE160170 dataset from the Gene Expression Omnibus (GEO) database, and the GEO2R online tool was used to obtain differentially expressed genes (DEGs). We searched for gout-related genes through the DisGeNET and GeneCards databases, and the final DEGs was acquired by intersection with the DEGs obtained from the microarray dataset. Tissue- and organ-specific genes were identified by the BioGPS online tool. Enrichment analysis was performed using GSEA4.1.0 and KOBAS3.0, and a protein-protein interaction (PPI) network was constructed using STRING to understand the biological functions and enrichment pathways of the DEGs as well as to identify their hub genes. Cytoscape was used to construct the competitive endogenous RNA (ceRNA) networks. RESULTS: A total of 653 differentially expressed lncRNAs (DElncRNAs) and 818 differentially expressed mRNAs (DEmRNAs) were identified in the present study. After intersecting the differential DEGs from the dataset, 85 DEGs were obtained. Enrichment analyses showed that the DEGs were mainly enriched in the following biological processes (BPs): inflammation and regulation; immune response; and cell proliferation and apoptosis. Moreover, the DEGs were mainly enriched in rheumatoid arthritis (RA), osteoclast differentiation, interleukin (IL)-17 signaling pathway, nuclear factor kappa B (NF-κB) signaling pathway, Toll-like receptor signaling pathway and tumor necrosis factor (TNF) signaling pathway. Cytoscape software identified 15 hub genes, and the following 9 hub genes were obtained after intersecting with genes specifically expressed in the blood/immune and bone/muscle systems: TNF, JUN, PTGS2, STAT1, IL6, FOS, IL1β, CXCL8 and CD80. In addition, the lncRNA-NEAT1-miR-142-3p-IL-6 pathway may be a key regulatory pathway in the pathogenesis of gout. CONCLUSIONS: The present study indicated that the identified 9 hub genes may be potential biomarkers for the diagnosis and treatment of gout. In addition, the results suggested that the lncRNA-NEAT1-miR-142-3p-IL-6 pathway may be a potential RNA regulatory pathway that controls the progression of gout disease.
35255727 Folate Receptor Expression by Human Monocyte-Derived Macrophage Subtypes and Effects of Co 2022 Jan OBJECTIVE: Folate receptor beta (FR-β) has been used as a clinical marker and target in multiple inflammatory diseases, including osteoarthritis (OA) and rheumatoid arthritis (RA). However, the conditions under which FR-β(+) macrophages arise remain unclear and could be affected by corticosteroids. Therefore, we studied FR-β expression in vitro in macrophage subtypes and determined their response to triamcinolone acetonide (TA), a clinically often-used corticosteroid. DESIGN: Human monocyte-derived macrophages were differentiated to the known M0, M1, or M2 macrophage phenotypes. The phenotype and FR-β expression and plasticity of the macrophage subtypes were determined using flow cytometry, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and enzyme-linked immunosorbent assay (ELISA). RESULTS: FR-β expression was low in granulocyte-macrophage colony-stimulating factor (GM-CSF)-generated (M1-like) macrophages and high in macrophage colony-stimulating factor (M-CSF)-generated (M0 and M2-like) macrophages. FR-β expression remained high once the M0 or M2 macrophages were stimulated with pro-inflammatory stimuli (interferon-γ plus lipopolysaccharide) to induce M1-like macrophages. On the contrary, anti-inflammatory TA treatment skewed GM-CSF macrophage differentiation toward an M2 and FR-β(+) phenotype. CONCLUSIONS: As corticosteroids skewed monocytes toward an FR-β-expressing, anti-inflammatory phenotype, even in an M1 priming GM-CSF environment, FR-β has potential as a biomarker to monitor success of treatment with corticosteroids. Without corticosteroid treatment, M-CSF alone induces high FR-β expression which remains high under pro-inflammatory conditions. This explains why pro-inflammatory FR-β(+) macrophages (exposed to M-CSF) are observed in arthritis patients and correlate with disease severity.
35360719 The Impact of Anti-rheumatic Drugs on the Seroprevalence of Anti-SARS-CoV-2 Antibodies in 2022 OBJECTIVES: Given the high occurrence of asymptomatic subsets, the true prevalence of SARS-CoV-2 infection in rheumatic patients is still underestimated. This study aims to evaluate the seroprevalence of SARS-CoV-2 antibodies in rheumatic musculoskeletal diseases (RMD) patients receiving immunomodulatory drugs. METHODS: All consecutive patients with rheumatoid arthritis or spondyloarthritis receiving disease-modifying antirheumatic drugs (DMARDs) evaluated between 4th May and 16th June 2020 were included. All participants were tested for anti-SARS-CoV-2 antibodies (IgG, IgM, IgA) by ELISA and were questioned about previous COVID-19 symptoms and clinical course. Results were compared with healthy population from the same region and with a control group of healthy subjects diagnosed with confirmed COVID-19. RESULTS: The study population includes 358 patients. The overall prevalence of anti-SARS-CoV-2 antibodies (18.4%) was higher than prevalence rate based on swab-positivity (1.12%) or clinically suspected cases (10.6%), but consistent with seroprevalence observed in the healthy population. Among seropositive patients 58% were asymptomatic. Mean anti-SARS-CoV-2 titer was comparable with the control group. No differences in seroprevalence were observed according to age, sex, rheumatic disease and treatment with conventional, biologic or targeted synthetic DMARDs, whereas glucocorticoids and comorbidities resulted in higher seroprevalence rate. CONCLUSIONS: The results of this study are reassuring about the low impact of RMDs and immunomodulatory therapies on the risk and clinical course of COVID-19 and on humoral immune response to SARS-CoV-2 infection.