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Associations between granulysin and ovarian endometriosis: A 2-sample Mendelian randomization study.

Endometriosis (EMS) is a chronic inflammatory disease defined by the presence of endometrial-like tissue outside the uterine cavity. Ovarian EMS is considered the most prevalent disease phenotype. However, the causal relationship between granulysin and ovarian EMS remains unclear. We investigate the potential causal relationship between granulysin and ovarian EMS using a 2-sample Mendelian randomization analysis. Genome-wide association study data for granulysin and ovarian EMS were obtained from publicly available online databases. A 2-sample Mendelian randomization analysis was conducted using the inverse-variance weighted method. The causal effect was further validated through weighted median and MR-Egger regression analyses, and a leave-one-out sensitivity analysis was performed. The odds ratio and its 95% confidence interval were used to evaluate the causal relationship between granulysin and the risk of ovarian EMS. Our findings suggest a direct causal relationship between granulysin expression and ovarian EMS. The inverse-variance weighted analysis revealed that a 1-standard deviation increase in granulysin was associated with a 10.7% reduction in the risk of ovarian EMS (odd ratio = 0.892, 95% confidence interval: 0.824-0.966, P = .004). There may exist a negative causal relationship between granulysin expression and ovarian EMS.

Female

An Immunosenescent CD8+ T Cell Subset in Patients with Axial Spondyloarthritis and Psoriatic Arthritis Links Spontaneous Motility to Telomere Shortening and Dysfunction.

OBJECTIVE: A pathogenetic role of CD8+ T lymphocytes in radiographic axial spondyloarthritis (r-axSpA) and other spondyloarthritis (SpA) is sustained by genome-wide association studies and by the expansion of public T cell clonotypes in the target tissues. This study investigates the migration of CD8+ T cells along with their phenotype and functions in patients with r-axSpA and psoriatic arthritis (PsA). METHODS: Peripheral blood CD8+ and CD4+ T cells were isolated from patients with r-axSpA (n = 128), PsA (n = 60), and rheumatoid arthritis (RA) (n = 74) and healthy donors (HDs) (n = 79). Transwell migration assay was performed in the presence of different chemokines. CD8+ T cell immunoprofiling and effector functions were assessed by multiparametric flow cytometry. Transcriptome signature was evaluated by RNA sequencing analysis, whereas telomere length and dysfunction were measured by reverse transcriptase-polymerase chain reaction and immunofluorescence-fluorescence in situ hybridization, respectively. RESULTS: A significantly higher number of CD8+ T cells migrating in the absence of chemokine stimuli was found in patients with SpA compared with HDs and patients with RA. This subset, producing cytotoxic (granzyme B, perforin, granulysin) and proinflammatory molecules (tumor necrosis factor), was significantly enriched in terminally differentiated (CCR7-CD45RA+) and senescent (CD28-CD57+) cells having a gene expression profile characterized by cytolytic signature and natural killer markers. Remarkably, these spontaneously migrating CD8+ T cells showed DNA damage response activation, telomere shortening, and dysfunction. CONCLUSION: These data describe a terminally differentiated CD8+ T cell subset with a senescent and cytotoxic/proinflammatory profile and an intrinsic invasive potential enriched in patients with SpA that represents a possible player in disease pathogenesis.

Humans