Objectives: Predicting the efficacy of biological disease-modifying antirheumatic drugs is challenging. In this study, we aimed to explore markers that predict the efficacy of abatacept in rheumatoid arthritis (RA) patients.
Methods: Thirty RA patients receiving abatacept were recruited, and peripheral blood mononuclear cells from the participants were subjected to DNA microarray analysis. The expression of CC chemokine receptor 4 (CCR4), which was selected by the result of DNA microarray, was determined by flow cytometry in 16 newly diagnosed treatment-naïve RA patients. CCR4 expression on each helper T-cell subset was also measured.
Results: CCR4 was upregulated in the abatacept responder. The expression levels of CCR4 were significantly correlated with the improvement of the Clinical Disease Activity Index. CCR4 expression was predominantly observed in CD4+ T cells in peripheral blood mononuclear cells. The percentage of CCR4-expressing CD4+ T cells was significantly higher in RA patients than in healthy individuals. Interestingly, Th17 and Treg cells expressed high levels of CCR4 compared to non-Th17-related helper T cells.
Conclusions: CCR4 is a Th17- and Treg-related gene, and the high CCR4 expression in peripheral blood samples may predict the efficacy of abatacept in RA.
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http://dx.doi.org/10.1093/mr/road077 | DOI Listing |
Sci Rep
December 2024
Department of Psychiatry and Behavioral Sciences and Weill Center for Neurosciences, University of California, San Francisco, CA, 94107, USA.
Telomere attrition is a hallmark of biological aging, contributing to cellular replicative senescence. However, few studies have examined the determinants of telomere attrition in vivo in humans. Mitochondrial Health Index (MHI), a composite marker integrating mitochondrial energy-transformation capacity and content, may be one important mediator of telomere attrition, as it could impact telomerase activity, a direct regulator of telomere maintenance.
View Article and Find Full Text PDFNat Commun
December 2024
Department of Vascular Surgery, Zhongshan Hospital, Fudan University, 200032, Shanghai, China.
Adverse aortic remodeling increases the risk of aorta-related adverse events (AAEs) after thoracic endovascular aortic repair (TEVAR) and affects the overall prognosis of aortic dissection (AD). It is imperative to delve into the exploration of prognostic indicators to streamline the identification of individuals at elevated risk for postoperative AAEs, and therapeutic targets to optimize the efficacy of TEVAR for patients with AD. Here, we perform proteomic and single-cell transcriptomic analyses of peripheral blood and aortic lesions, respectively, from patients with AD and healthy subjects.
View Article and Find Full Text PDFNat Commun
December 2024
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Hodgkin Reed-Sternberg (HRS) cells of classic Hodgkin lymphoma (cHL), like many solid tumors, elicit ineffective immune responses. However, patients with cHL are highly responsive to PD-1 blockade, which largely depends on HRS cell-specific retention of MHC class II and implicates CD4 T cells and additional MHC class I-independent immune effectors. Here, we utilize single-cell RNA sequencing and spatial analysis to define shared circulating and microenvironmental features of the immune response to PD-1 blockade in cHL.
View Article and Find Full Text PDFHere we report results of a phase 1 multi-institutional, open-label, dose-escalation trial (NCT02744287) of BPX-601, an investigational autologous PSCA-directed GoCAR-T® cell product containing an inducible MyD88/CD40 ON-switch responsive to the activating dimerizer rimiducid, in patients with metastatic pancreatic (mPDAC) or castration-resistant prostate cancer (mCRPC). Primary objectives were to evaluate safety and tolerability and determine the recommended phase 2 dose/schedule (RP2D). Secondary objectives included the assessment of efficacy and characterization of the pharmacokinetics of rimiducid.
View Article and Find Full Text PDFElife
December 2024
Department of Dermatology, Course of Integrated Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan.
Psoriasis is a multifactorial disorder mediated by IL-17-producing T cells, involving immune cells and skin-constituting cells. Semaphorin 4A (Sema4A), an immune semaphorin, is known to take part in T helper type 1/17 differentiation and activation. However, Sema4A is also crucial for maintaining peripheral tissue homeostasis and its involvement in skin remains unknown.
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