The aim of this meta-analysis was to compare health-related quality of life (HRQoL) of Osteoarthritis (OA) patients and controls. A systematic literature search was performed on PubMed, Web of Science and EMBASE from database inception to 7 January 2020. Random effect model was performed to summarize the scores of each domain and the forest plot was used to compare the scores of OA patients with healthy controls. Subgroup analyses were conducted to explore the source of heterogeneity. Statistical analyses were executed using Review Manager (version 5.1). In total, six studies were included in this study, including 7094 patients with OA and 12 100 healthy controls, which were all reliable to summarize the scores of the Medical Outcomes Study 36-item Short-Form Health Survey (SF-36). Meta-analyses found that pooled mean HRQoL score for the SF-36 each domain (physical function, physical role function, body pain, general health, vitality, social function, emotional role function, mental health) was lower in patients with OA than in healthy controls, especially the score in the dimension of physical role function. OA have a substantial impact HRQoL. HRQoL is a significant component of measuring overall health, which contributes to formulate successful self-disease management plan, patient-centered care, and develop effective interventions target confidence.
Pyroptosis, an inflammatory form of programmed cell death, is linked to the pathology of rheumatoid arthritis (RA). Here, we investigated the molecular mechanism underlying pyroptosis in T cells isolated from patients with RA. Compared with healthy individuals, patients with RA had more pyroptotic CD4 + T cells in blood and synovia, which correlated with clinical measures of disease activity. Moreover, the mRNA expression and protein abundance of arachidonate 5-lipoxygenase (ALOX5), which converts arachidonic acid to leukotriene A 4 (LTA 4 ), were increased in CD4 + T cells from patients with RA and, among patients with RA, were lowest in those in clinical remission. Knockdown or pharmacological inhibition of ALOX5 suppressed CD4 + T cell pyroptosis and improved symptoms in two rodent models of RA. Mechanistically, the increase in ALOX5 activity in RA CD4 + T cells enhanced the production of the LTA 4 derivative LTB 4 , which stimulated Ca 2+ influx through ORAI3 channels, leading to the activation of NLRP3 inflammasomes and pyroptosis. Our findings reveal a role for ALOX5 in RA and provide a molecular basis for further exploring the clinical utility of ALOX5 inhibition in RA and for using ALOX5 as a biomarker to distinguish active disease and remission in RA.
Centenarians, who show mild infections and low incidence of tumors, are the optimal model to investigate healthy aging. However, longevity related immune characteristics has not been fully revealed largely due to lack of appropriate controls. In this study, single‐cell transcriptomic analysis of peripheral blood mononuclear cells (PBMCs) derived from seven centenarians (CEN), six centenarians’ offspring (CO), and nine offspring spouses or neighbors (Control, age‐matched to CO) are performed to investigate the shared immune features between CEN and CO. The results indicate that among all 12 T cell clusters, the cytotoxic‐phenotype‐clusters (CPC) and the naïve‐phenotype‐clusters (NPC) significantly change between CEN and ontrol. Compared to Control, both CEN and CO are characterized by depleted NPC and increased CPC, which is dominated by CD8+ T cells. Furthermore, CPC from CEN and CO share enhanced signaling pathways and transcriptional factors associated with immune response, and possesse similar T‐cell‐receptor features, such as high clonal expansion. Interestingly, rather than a significant increase in GZMK+ CD8 cells during aging, centenarians show accumulation of GZMB+ and CMC1+ CD8 T cells. Collectively, this study unveils an immune remodeling pattern reflected by both quantitative increase and functional reinforcement of cytotoxic T cells which are essential for healthy aging.
Objective: The peripheral B cell compartment is heavily disturbed in systemic lupus erythematosus (SLE), but whether B cells develop aberrantly in the bone marrow (BM) is largely unknown.Methods: We performed single‐cell RNA/B cell receptor (BCR) sequencing and immune profiling of BM B cells and classified patients with SLE into two groups: early B cell (Pro‐B and Pre‐B) normal (EBnor) and EB defective/low (EBlo) groups.Results: The SLE‐EBlo group exhibited more severe disease activity and proinflammatory status, overaction of type I interferon signaling and metabolic pathways within the B cell compartment, and aberrant BCR repertoires compared with the SLE‐EBnor group. Moreover, in one patient with SLE who was initially classified in the SLE‐EBlo group, early B cell deficiency and associated abnormalities were largely rectified in a second BM sample at the remission phase.Conclusion: In summary, this study suggests that early B cell loss in BM defines a unique pathological state in a subset of patients with SLE that may play an active role in the dysregulated autoimmune responses.