Causal relationships between CD25 on immune cells and hip osteoarthritis

Abstract

ObjectivesPrevious research has indicated a potential association between immune factors and osteoarthritis (OA), but the causal relationship between CD25 expression on immune cells and hip OA remains enigmatic. To shed light on this relationship, this study utilized the two-sample Mendelian Randomization (MR) method.MethodsLeveraging genome-wide association studies (GWAS) data from the UK Biobank and arcOGEN, the investigation encompasses a substantial European cohort comprising 15,704 hip OA cases and 378,169 controls. Genetic insights into CD25 stem from a subgroup of 3,757 individuals with European ancestry, encompassing 77 CD25-related traits. Several MR methods were applied, and robustness was assessed through heterogeneity and sensitivity analysis.ResultsAmong the 77 traits examined, 66 shared the same single nucleotide polymorphisms (SNPs) with hip OA. Of these, 7 CD25-related traits were found to be causally associated with hip OA (adjusted P><0.05), with F-statistics ranging from 33 to 122. These traits are specifically related to CD4+CD25+ T cells, exhibiting odds ratios (OR) and 95% confidence intervals (CI) less than 1. Notably, no causal link was discerned with the CD8+CD25+ T cell subset. Within absolute count (AC) and relative count (RC) trait types, a significant causal relationship was observed solely between CD4+CD25+ T cells and hip OA, without subtype localization. A more intricate examination of CD25 expression levels within the CD4+CD25+ T cell subset revealed a correlation with the CD39+ regulatory T (Treg) subset and hip OA, particularly within the CD39+ activated Treg subset. Furthermore, a notable causal relationship emerged between CD25 expression levels in the CD45RA- not Treg subset and hip OA. However, no significant causal link was established with any subsets of B cells.ConclusionThe genetic prediction suggests that CD25, particularly within the realm of CD4+CD25+ T cells, may exert a protective influence against the development of hip OA. These findings provide a novel therapeutic approach for the prevention and treatment of hip OA.

Causal relationship between immune cells and osteoarthritis: a two-sample Mendelian randomization study

“…With increasing research on T cell subsets, a group of cells capable of actively maintaining immune homeostasis and peripheral immune tolerance has been identi ed and de ned as Tregs (21). CD4 + CD25 + Tregs are negative immunoregulatory cells that play key roles in inhibiting the progression of autoimmune diseases, controlling potentially harmful in ammatory responses, and maintaining autoimmune homeostasis (22,23). Consequently, more CD25-expressing Tregs or higher CD25 expression levels can improve Treg function, which is essential for preventing the development of immunological in ammation.…”

Association of peripheral inflammatory indicators with osteoarthritis risk

“…In this view, the aggregation of neutrophils around the joints and the destruction of articular cartilage by neutrophil elastase (NE) are considered indispensable for the progression of OA [ 31 , 32 ]. A recent Mendelian randomization (MR) analysis also revealed a causal association between adaptive immune T cells and a reduced risk of hip OA [ 33 ]. Similarly, our study found that adaptively immunized lymphocytes and LMR were associated with a lower risk of OA.…”

The Relationship Between Circulating Immune Cell Phenotypes and Sepsis: A Mendelian Randomization Study

“…Recognizing the diverse genetic backgrounds of populations, substantial variations in the frequency of genetic variants exist. This inherent diversity poses the risk of spurious associations between genetic variations and outcomes (11). To address this concern, we restricted the sources of GWAS data for both exposure and outcomes to the European population.…”

“…In the field of epidemiological research, traditional observational studies often introduce bias to research results owing to potential confounding factors and reverse causation, thereby compromising their reliability (11). Although randomized controlled trials (RCTs) can address the limitations present in observational studies, the considerable time, manpower, and financial resources required for them become a significant and unavoidable challenge (12).…”