Dendritic cells (DCs) play crucial roles in the pathogenesis of rheumatoid arthritis (RA), a prototypic autoimmune disease characterized by chronic synovitis and joint destruction. Conventional ...dendritic cells (cDCs) with professional antigen-presenting functions are enriched in the RA synovium. In the synovium, the cDCs are activated and show both enhanced migratory capacities and T cell activation in comparison with peripheral blood cDCs. Plasmacytoid dendritic cells, another subtype of DCs capable of type I interferon production, are likely to be tolerogenic in RA. Monocyte-derived dendritic cells (moDCs), once called "inflammatory DCs", are localized in the RA synovium, and they induce T-helper 17 cell expansion and enhanced proinflammatory cytokine production. Recent studies revealed that synovial proinflammatory hypoxic environments are linked to metabolic reprogramming. Activation of cDCs in the RA synovium is accompanied by enhanced glycolysis and anabolism. In sharp contrast, promoting catabolism can induce tolerogenic DCs from monocytes. Herein, we review recent studies that address the roles of DCs and their immunometabolic features in RA. Immunometabolism of DCs could be a potential therapeutic target in RA.
•Heat treatment of soybean seeds only partially denatured the protein.•The oil distribution in soybean seeds changed after heat treatment.•Lipoxygenase was susceptible to heat ...denaturation.•Microwaves are effective in changing the properties of the soybean components.
The effects of autoclave and microwave heating on the protein and oil in soybean seeds were investigated under low moisture conditions. The nitrogen solubility index (NSI) decreased on heating. The reduction in the NSI was accompanied by an increase in the size and deformation of the oil bodies in the cellular tissue of soybean seeds. Sodium dodecyl sulfate–polyacrylamide gel electrophoresis analysis revealed that lipoxygenase was susceptible to heat denaturation, but 7S and 11S globulins were only partially denatured. The partial denaturation of the proteins was confirmed by Fourier transform infrared spectroscopy measurements. The ratio of oil to protein peaks increased with increasing heating, suggesting the exudation of oil to the surface or outside of oil bodies. Microwave heating is more efficient in changing the oil distribution in soybean seeds than autoclave heating. On the other hand, the degree of protein denaturation is lower after microwave heating.
In a super-aging society, medical-dental collaboration is increasingly vital for comprehensive patient care. Particularly in dysphagia rehabilitation and perioperative oral functional management, ...dental hygienists' active involvement is pivotal to interprofessional collaborative practice. Despite this societal expectation, dental hygienists' experiences and perceptions of interprofessional collaboration have not been explored. This study aims to investigate dental hygienists' interprofessional identity formation and perceptions of interprofessional collaboration. Specifically, it was explored from the perspectives of dental hygiene students and hospital dental hygienists.
This study is underpinned by Wenger's social theory of learning, which focuses on identity as a component in the process of learning in communities. Semi-structured interviews were conducted with 11 dental hygiene students in their final year at a technical college and five dental hygienists engaging in interprofessional care at a university hospital in Japan. The narrative data were analysed using an inductive approach to thematic analysis to extract themes regarding the identification of self in interprofessional teams.
Dental hygiene students found several barriers to the collaboration, including power relation and conceptual hierarchy, limited understanding of other professional roles, and differences in language and jargon. They viewed themselves as inferior in the interprofessional team. This resulted from their limited knowledge about general health and less responsibility for problems directly related to patient life and death. However, they could ultimately perceive the negative experiences positively as challenges for the future through reflection on learning in clinical placements. Contrarily, dental hygienists did not have such negative perceptions as the students did. Rather, they focused on fulfilling their roles as dental professionals in the interprofessional team. Their identities were formed through actively involving, coordinating their activity, and creating new images of the world and self in inter-professional communities of practice.
Interprofessional identity is relational as well as experiential, which is developed in complex and socially dynamic processes across intra- and inter-professional communities of practice. Engagement, imagination, and alignment are essential aspects of their interprofessional identities, which inform conceptual foundations of interprofessional education and collaborative practice in health care.
Early diagnosis and timely therapeutic intervention are clinical challenges of rheumatoid arthritis (RA), especially for treatment-resistant or difficult-to-treat patients. Little is known about the ...immunological mechanisms involved in refractory RA. In this review, we summarize previous research findings on the immunological mechanisms of treatment-resistant RA. Genetic prediction of treatment-resistant RA is challenging. Patients with and without anti-cyclic citrullinated peptide autoantibodies are considered part of distinct subgroups, especially regarding long-term clinical prognosis and treatment responses. B cells, T cells and other immune cells and fibroblasts are of pathophysiological importance and are associated with treatment responses. Finally, we propose a new hypothesis that stratifies patients with RA into two subgroups with distinct immunological pathologies based on our recent immunomics analysis of RA. One RA subgroup with a favorable prognosis is characterized by increased interferon signaling. Another subgroup with a worse prognosis is characterized by enhanced acquired immune responses. Increases in dendritic cell precursors and diversified autoreactive anti-modified protein antibodies may have pathophysiological roles, especially in the latter subgroup. These findings that improve treatment response predictions might contribute to future precision medicine for RA.
Thrombotic microangiopathies (TMAs) rarely accompany polymyositis/dermatomyositis. We treated three patients with dermatomyositis combined with TMA. A literature review identified 13 previously ...reported cases. Exacerbation of myositis at the time of the TMA onset was observed in 62.5% of all patients, suggesting that the TMA onset may be associated with autoantibody production. We also found that cases of TMA with polymyositis/dermatomyositis often had a poor treatment response rate (37.5%). Furthermore, even if treatment was effective, the mortality rate associated with subsequent complications was high, and the survival rate was low (18.8%). Therefore, careful attention should be paid to patient management after TMA treatment.
Previous gene expression analyses seeking genes specific to antineutrophil cytoplasmic antibody-associated vasculitis (AAV) have been limited due to crude cell separation and the use of microarrays. ...This study aims to identify AAV-specific gene expression profiles in a way that overcomes those limitations.
Blood samples were collected from 26 AAV patients and 28 healthy controls (HCs). Neutrophils were isolated by negative selection, whereas 19 subsets of peripheral blood mononuclear cells were sorted by fluorescence assisted cell sorting. RNA-sequencing was then conducted for each sample, and iterative weighted gene correlation network analysis (iterativeWGCNA) and random forest were consecutively applied to identify the most influential gene module in distinguishing AAV from HCs. Correlations of the identified module with clinical parameters were evaluated, and the biological role was assessed with hub gene identification and pathway analysis. Particularly, the module's association with neutrophil extracellular trap formation, NETosis, was analyzed. Finally, the module's overlap with GWAS-identified autoimmune disease genes (GADGs) was assessed for validation.
A neutrophil module (Neu_M20) was ranked top in the random forest analysis among 255 modules created by iterativeWGCNA. Neu_M20 correlated with disease activity and neutrophil counts but not with the presence of antineutrophil cytoplasmic antibody. The module comprised pro-inflammatory genes, including those related to NETosis, supported by experimental evidence. The genes in the module significantly overlapped GADGs.
We identified the distinct group of pro-inflammatory genes in neutrophils, which characterize AAV. Further investigations are warranted to confirm our findings as they could serve as novel therapeutic targets.
•Expression profile of a gene module in neutrophils characterizes AAV.•The module eigengene correlates with disease activity and neutrophil counts.•The module comprises pro-inflammatory genes, including those related to NETosis.•Genes in the module overlap autoimmune disease genes identified by GWAS.
Objective
Idiopathic inflammatory myopathies (IIM) demonstrate characteristic clinical phenotypes depending on the myositis‐specific antibody (MSAs) present. We aimed to identify common or ...MSA‐specific immunological pathways in different immune cell types from peripheral blood by transcriptome analysis.
Methods
We recruited 33 patients with IIM who were separated into the following groups: 15 patients with active disease at onset and 18 with inactive disease under treatment. All patients were positive for MSAs: anti–melanoma differentiation‐associated gene 5 (MDA5) antibody (Ab) in 10 patients, anti‐Mi‐2 Ab in 7, and anti‐aminoacyl‐transfer RNA synthetase (ARS) Ab in 16. The patients were compared with 33 healthy controls. Twenty‐four immune cell types sorted from peripheral blood were analyzed by flow cytometry, RNA sequencing, and differentially expressed gene analysis combined with pathway analysis.
Results
The frequencies of memory B cell types were significantly decreased in active patients, and the frequency of plasmablasts was prominently increased in active patients with anti‐MDA5 Ab in comparison with healthy controls. The expression of type I interferon (IFN)‐stimulated genes of all immune cell types was increased in the active, but not inactive, patients. Endoplasmic reticulum stress‐related genes in all IIM memory B cells and oxidative phosphorylation‐related genes in inactive IIM double negative B cells were also increased, suggesting prominent B cell activation in IIM. Furthermore, active patients with anti‐MDA5 Ab, anti‐Mi‐2 Ab, or anti‐ARS Ab were distinguished by IFN‐stimulated and oxidative phosphorylation‐related gene expression in plasmablasts.
Conclusion
Unique gene expression patterns in patients with IIM with different disease activity levels and MSA types suggest different pathophysiologies. Especially, B cells may contribute to common and MSA‐specific immunological pathways in IIM.
Overlap syndrome refers to a group of conditions that have clinical features of more than one well-characterised rheumatic disease and meet the respective classification criteria. There are no ...typical renal histological findings in overlap syndrome. When patients with overlap syndrome develop renal dysfunction, various potential causes, including lupus nephritis (LN), renal crisis by systemic sclerosis, interstitial nephritis, and so on, need to be distinguished. Here, we report a 44-year-old woman with overlap syndrome involving systemic lupus erythematosus (SLE), diffuse cutaneous systemic scleroderma, and Sjogren's syndrome, who was also positive for anti-mitochondrial M2 antibody. She developed glomerular haematuria, proteinuria, and increase in creatinine appeared gradually. Suspecting LN, renal biopsy was performed. However, in the interstitium, mild infiltration of lymphocytes and plasma cells and very partial fibrosis were observed. Immunofluorescence microscopy revealed predominant mesangial immunoglobulin M, C3, and λ light chain staining. Overall, LN was not diagnosed based on these findings. Renal dysfunction was normalised by glucocorticoid treatment for 3 months. This case suggests the importance of a renal diagnosis based on renal pathological findings, especially in a case of overlap syndrome including SLE.
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