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Arthritis & Rheumatology (Hoboken, N.J.) Jul 2024
PubMed: 38961026
DOI: 10.1002/art.42945 -
Immunologic Research Jul 2024The mucosal origin hypothesis of rheumatoid arthritis has renewed the interest in IgA autoantibodies, but their added value over IgG anti-citrullinated protein antibody...
The mucosal origin hypothesis of rheumatoid arthritis has renewed the interest in IgA autoantibodies, but their added value over IgG anti-citrullinated protein antibody (ACPA) and IgM rheumatoid factor (RF) for modern treatment outcomes remains unknown. We aimed to investigate the prognostic value of IgA-ACPA and IgA-RF for treatment outcomes in an early arthritis population. IgA-ACPA/RF isotypes were measured in baseline sera from 480 inflammatory arthritis (IA) patients, who were included in the treatment in the Rotterdam Early Arthritis Cohort trial (tREACH). The tREACH trial was a multicentre, stratified, single-blinded trial with a treat-to-target approach. The prognostic value of IgA-ACPA/RF was determined by evaluating differences in (1) quick-attained (< 6 months after diagnosis) and persistent remission rates, (2) DMARD-free remission and (3) biological use between IA patients with and without IgA-ACPA/RF over 3 years of follow-up. IgA-ACPA was present in 23% of patients and overlapped with IgG-ACPA positivity in 94%. Similarly, IgA-RF overlapped with IgM-RF in 90% of patients. IgA-ACPA positivity was associated with lower DFR rates and more biological use, but this effect was largely mediated by the presence of IgG-ACPA, since this effect disappeared after stratification for IgG-ACPA (HR 0.6, 95%CI 0.2-1.6 for DFR). No differences were observed in 'quick-attained and persistent remission' rates and for IgA-RF. Their seems to be no additional value of IgA-ACPA and IgA-RF for modern, long-term clinical outcomes. The effects of IgA-ACPA seen in our study are largely mediated by the presence of IgG-ACPA. Based on these results, there is no rationale for measuring these isotypes in daily practice.
PubMed: 38960995
DOI: 10.1007/s12026-024-09500-w -
Osteoporosis International : a Journal... Jul 2024Task Force on 'Clinical Algorithms for Fracture Risk' commissioned by the American Society for Bone and Mineral Research (ASBMR) Professional Practice Committee has...
Task Force on 'Clinical Algorithms for Fracture Risk' commissioned by the American Society for Bone and Mineral Research (ASBMR) Professional Practice Committee has recommended that FRAX® models in the US do not include adjustment for race and ethnicity. This position paper finds that an agnostic model would unfairly discriminate against the Black, Asian and Hispanic communities and recommends the retention of ethnic and race-specific FRAX models for the US, preferably with updated data on fracture and death hazards. In contrast, the use of intervention thresholds based on a fixed bone mineral density unfairly discriminates against the Black, Asian and Hispanic communities in the US. This position of the Working Group on Epidemiology and Quality of Life of the International Osteoporosis Foundation (IOF) is endorsed both by the IOF and the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO).
PubMed: 38960982
DOI: 10.1007/s00198-024-07162-w -
Journal of Occupational Rehabilitation Jul 2024The objectives of this longitudinal study were to understand how comorbid rheumatic disease and depression symptoms were associated with at-work productivity among young...
BACKGROUND
The objectives of this longitudinal study were to understand how comorbid rheumatic disease and depression symptoms were associated with at-work productivity among young adults, and to examine whether workplace support modified this association.
METHODS
Seventy-six Canadian young adults who were employed and living with a rheumatic disease were surveyed three times over 27 months. Morbidity was defined by whether participants reported severe rheumatic disease symptoms and/or depressive symptoms. Participants were asked about presenteeism, absenteeism, and whether the workplace support needs (accommodation and benefit availability and use) were met. Generalized estimating equations were used to address study objectives.
RESULTS
Seventeen participants experienced neither severe rheumatic disease nor depressive symptoms (no morbidity), 42 participants experienced either severe rheumatic disease or depressive symptoms (single morbidity), and 17 participants reported comorbidity at baseline. Participants with comorbidity reported greater presenteeism scores and were most likely to report absenteeism, compared to the other two morbidity levels. Having workplace support needs met was associated with decreased presenteeism over the 27-month period among participants with no and a single morbidity. Conversely, unmet support need was associated with greater presenteeism for participants with comorbidity. Having workplace support needs met did not modify the association between morbidity and absenteeism.
CONCLUSION
Comorbid rheumatic disease and depression burden reduce productivity among young adults. A supportive work environment has the potential to address at-work productivity challenges. Additional research is needed to understand how workplace supports coupled with clinical interventions may tackle challenges at work for young adults living with rheumatic disease and depression.
PubMed: 38960928
DOI: 10.1007/s10926-024-10217-8 -
JACC. Heart Failure Jul 2024
Topics: Humans; Cardiorespiratory Fitness; Heart Failure; Inflammation; Stroke Volume
PubMed: 38960521
DOI: 10.1016/j.jchf.2024.05.004 -
Advances in Protein Chemistry and... 2024TMEM230 promotes antigen processing, trafficking, and presentation by regulating the endomembrane system of membrane bound organelles (lysosomes, proteosomes and... (Review)
Review
TMEM230 promotes antigen processing, trafficking, and presentation by regulating the endomembrane system of membrane bound organelles (lysosomes, proteosomes and mitochondria) and phagosomes. Activation of the immune system requires trafficking of various cargos between the endomembrane system and cell plasma membrane. The Golgi apparatus is the hub of the endomembrane system and essential for the generation, maintenance, recycling, and trafficking of the components of the endomembrane system itself and immune system. Intracellular trafficking and secretion of immune system components depend on mitochondrial metalloproteins for ATP synthesis that powers motor protein transport of endomembrane cargo. Glycan modifying enzyme genes and motor proteins are essential for the activation of the immune system and trafficking of antigens between the endomembrane system and the plasma membrane. Recently, TMEM230 was identified as co-regulated with RNASET2 in lysosomes and with metalloproteins in various cell types and organelles, including mitochondria in autoimmune diseases. Aberrant metalloproteinase secretion by motor proteins is a major contributor to tissue remodeling of synovial membrane and joint tissue destruction in rheumatoid arthritis (RA) by promoting infiltration of blood vessels, bone erosion, and loss of cartilage by phagocytes. In this study, we identified that specific glycan processing enzymes are upregulated in certain cell types (fibroblast or endothelial cells) that function in destructive tissue remodeling in rheumatoid arthritis compared to osteoarthritis (OA). TMEM230 was identified as a regulator in the secretion of metaloproteinases and heparanase necessary tissue remodeling in OA and RA. In dendritic (DC), natural killer and T cells, TMEM230 was expressed at low or no levels in RA compared to OA. TMEM230 expression in DC likely is necessary for regulatory or helper T cells to maintain tolerance to self-antigens and prevent susceptibility to autoimmune disease. To identify how TMEM230 and the endomembrane system contribute to autoimmunity we investigated, glycan modifying enzymes, metalloproteinases and motor protein genes co-regulated with or regulated by TMEM230 in synovial tissue by analyzing published single cell transcriptomic datasets from RA patient derived synovial tissue.
Topics: Humans; Metalloproteins; Single-Cell Analysis; Autoimmunity; Membrane Proteins; Animals; Gene Expression Profiling
PubMed: 38960478
DOI: 10.1016/bs.apcsb.2024.03.007 -
BMJ Case Reports Jul 2024Sjogren's syndrome is a known cause of renal tubular acidosis (RTA). However, osteomalacia associated with Sjogren's syndrome is rare and seldom reported in literature....
Sjogren's syndrome is a known cause of renal tubular acidosis (RTA). However, osteomalacia associated with Sjogren's syndrome is rare and seldom reported in literature. We report a case of pseudofractures of both femora due to osteomalacia as a result of RTA secondary to Sjogren's syndrome, which was initially misdiagnosed as a stress fracture. A man in his 30s presented with hip pain and was initially misdiagnosed to have stress fractures because of the 'through and through' extension of the 'fracture' lines at the neck of both femora. The patient had a normal serum biochemistry profile except for elevated alkaline phosphatase levels. On further evaluation, he was found to have distal RTA secondary to Sjogren's syndrome. The patient responded to sodium bicarbonate therapy with clinical, biochemical and radiological improvement. A high index of suspicion for RTA should be kept in a patient with osteomalacia with a normal calcium profile and vitamin D level.
Topics: Humans; Sjogren's Syndrome; Male; Osteomalacia; Adult; Acidosis, Renal Tubular; Diagnosis, Differential; Fractures, Stress; Sodium Bicarbonate
PubMed: 38960417
DOI: 10.1136/bcr-2023-256661 -
International Journal of Pharmaceutics Jul 2024Bulleyaconitine A (BLA) is a promising candidate for treating rheumatoid arthritis (RA) with diverse pharmacological activities, including anti-inflammatory, analgesic...
Bulleyaconitine A (BLA) is a promising candidate for treating rheumatoid arthritis (RA) with diverse pharmacological activities, including anti-inflammatory, analgesic and bone repair. Herein, the long-acting bulleyaconitine A microspheres (BLA-MS) were developed to treat RA comprehensively by forming drug reservoirs in joint cavities. The BLA-MS were prepared by emulsion/solvent evaporation method. The particle size and distribution were assessed by SEM. The crystalline state was investigated by DSC and PXRD. The drug loading (DL), encapsulation efficiency (EE) and cumulative release in vitro were determined by HPLC. The DL and EE were 23.93 ± 0.38 % and 95.73 ± 1.56 % respectively, and the cumulative release was up to 69 days with a stable release curve. The pharmacodynamic results in collagen induced arthritis (CIA) rats showed a noticeable reduction in paw thickness (5.66 ± 0.32 mm), and the decreasing expression level of PGE, TNF-α and IL-6 which diminished the infiltration of inflammatory cells, thereby alleviating the progression of erosion and repairing the damaged bones (BV/TV (Bone Volume / Total Volume): 81.97 %, BS/BV (Bone Surface / Bone Volume): 6.08 mm). In conclusion, intra-articular injection of BLA-MS should have a promising application in the treatment of RA and may achieve clinical transformation in the future.
PubMed: 38960344
DOI: 10.1016/j.ijpharm.2024.124414 -
Bone Jul 2024X-linked Hypophosphatemia (XLH) is the most common type of inherited rickets. Although the clinical features are well characterized, bone structure, mineralization, and...
X-linked Hypophosphatemia (XLH) is the most common type of inherited rickets. Although the clinical features are well characterized, bone structure, mineralization, and biomechanical properties are poorly known. Our aim was to analyze bone properties in the appendicular and axial skeleton of adults with XLH. In this observational case-control study, each affected patient (N = 14; 9 females; age 50 ± 15 years) was matched by sex, age and body mass index to a minimum of two healthy controls (N = 34). Dual-energy X-ray Absorptiometry (DXA) analyses revealed that areal bone mineral density (aBMD) was higher in XLH patients at the lumbar spine (Z score mean difference = +2.47 SD, P value = 1.4 × 10). Trabecular Bone Score was also higher at the lumbar spine (P value = 1.0 × 10). High Resolution peripheral Quantitative Computed Tomography (HRpQCT) demonstrated that bone cross-sectional area was larger at the distal radius (P value = 6 × 10). Total and trabecular volumetric BMD were lower at both sites. Trabecular bone volume fraction was also lower with fewer trabecular numbers at both sites. However, bone strength evaluated by micro-finite element analyzes revealed unaffected bone stiffness and maximum failure load. Evaluation of bone mineralization with aBMD by DXA at the distal radius correlated with vBMD by HRpQCT measurements at both sites. PTH levels were inversely correlated with trabecular vBMD and BV/TV at the tibia. We then followed a subset of nine patients (median follow-up of 4 years) and reassessed HRpQCT. At the tibia, we observed a greater decrease than expected from an age and sex standardized normal population in total and cortical vBMD as well as a trabecularization of the cortical compartment. In conclusion, in adult patients with XLH, bone mineral density is high at the axial skeleton but low at the appendicular skeleton. With time, microarchitectural alterations worsen. We propose that noninvasive evaluation methods of bone mineralization such as DXA including the radius should be part of the management of XLH patients. Larger studies are needed to evaluate the clinical significance of BMD changes in XLH patients under conventional or targeted therapies.
PubMed: 38960298
DOI: 10.1016/j.bone.2024.117179 -
Osteoarthritis and Cartilage Jul 2024Synovitis is a widely accepted sign of osteoarthritis (OA), characterised by tissue hyperplasia, where increased infiltration of immune cells and proliferation of... (Review)
Review
Immunomodulation and fibroblast dynamics driving nociceptive joint pain within inflammatory synovium: Unravelling Mechanisms for Therapeutic Advancements in Osteoarthritis.
OBJECTIVE
Synovitis is a widely accepted sign of osteoarthritis (OA), characterised by tissue hyperplasia, where increased infiltration of immune cells and proliferation of resident fibroblasts adopt a pro-inflammatory phenotype, and increased the production of pro-inflammatory mediators that are capable of sensitising and activating sensory nociceptors, which innervate the joint tissues. As such it is important to understand the cellular composition of synovium and their involvement in pain sensitisation to better inform the development of effective analgesics.
METHODS
Studies investigating pain sensitisation in OA with a focus on immune cells and fibroblasts were identified using PubMed, Web of Science and SCOPUS.
RESULTS
In this review, we comprehensively assess the evidence that cellular crosstalk between resident immune cells or synovial fibroblasts with joint nociceptors in inflamed OA synovium contribute to peripheral pain sensitisation. Moreover, we explore whether elucidation of common mechanisms identified in similar joint conditions may inform the development of more effective analgesics specifically targeting OA joint pain.
CONCLUSION
The concept of local environment and cellular crosstalk within the inflammatory synovium as a driver of nociceptive joint pain presents a compelling opportunity for future research and therapeutic advancements.
PubMed: 38960140
DOI: 10.1016/j.joca.2024.06.011