Reduced TRIM expression correlates with anomalous CD4 T cell activation in systemic lupus Erythematosus and its clinical diagnostic potential.

OBJECTIVE: This study seeks to elucidate the expression, function, and clinical relevance of the T cell receptor interacting molecule (TRIM) within circulating CD4+T cell subsets in systemic lupus erythematosus (SLE) patients. METHODS: We assessed TRIM expression across distinct subpopulations of human peripheral blood mononuclear cells (PBMCs) through the analysis of publicly available single-cell RNA sequencing data. In addition, TRIM expression was investigated within CD4+T cell subsets of peripheral blood and spleens in mice. PBMCs were isolated from both SLE patients, healthy controls (HCs) and rheumatoid arthritis (RA) patients with subsequent measurement and comparative analysis of TRIM expression and functional molecules using flow cytometry. To gauge the clinical relevance of TRIM in SLE, correlation and ROC curve analyses were performed. RESULTS: In both healthy humans and mice, TRIM was higher expressed within CD4+T cell subsets, especially in naive CD4+T cells. TRIM+ Tregs exhibited lower Helios+ cells and CD45RA-FoxP3hi cells percentages compared to TRIM- Treg cells. TRIM+T cells demonstrated reduced granzyme B and perforin secretion and increased IFN-γ secretion in comparison to TRIM- T cells. Notably, the proportion of TRIM+CD4+T cells was diminished in SLE patients. The downregulation of TRIM+ in CD4+T cells positively correlated with diminished complement C3 and C1q levels and inversely correlated with CRP. The identification of TRIM-associated CD4 T cell subsets aids in distinguishing SLE patients from HCs and those with RA. CONCLUSIONS: Reduced TRIM expression is linked to abnormal CD4+T cell activation in SLE. TRIM-associated CD4+T cells may be implicated in the pathogenesis of SLE and hold potential for clinical diagnostic purposes.

Expression of GPR56 reflects a hypoactivated state of circulating B cells and is downregulated in B cell subsets in patients with early-stage lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is the most prevalent subtype of lung cancer, and the early detection and diagnosis of this disease are crucial in reducing mortality rates. The timely diagnosis of LUAD is essential for controlling tumour development and enabling early surgical treatment. GPR56 is a vital G protein-coupled receptor and its role in T lymphocytes has received considerable attention. However, its function in B cells remains unclear. This study aimed to investigate the significance of GPR56 in LUAD. We found that GPR56 exhibited a significant increase in circulating plasmablasts and a decrease in new memory B cells. GPR56 expression in B cells was significantly reduced after LPS stimulation and the proportion of HLA-DR+ and CD40+ proportions were also decreased in GPR56+ B cells after stimulation. Additionally, GPR56 exhibited significant down-regulation in circulating B cell subsets of early-stage LUAD patients, and there were significant correlations between GPR56+ B cell subsets and tumour markers. In conclusion, GPR56 could reflect the hypoactivation state of B cells and the decreased proportion of GPR56+ B cell subset in LUAD patients can signify the active humoral immunity in vivo. The expression of GPR56 in B cells could potentially hold value in the early diagnosis of LUAD.

Differential GPR56 Expression in T Cell Subpopulations for Early-Stage Lung Adenocarcinoma Patient Identification.

OBJECTIVE: This study aimed to investigate the expression of GPR56 in the T cells of early-stage lung adenocarcinoma (LUAD) patients and clarify its diagnostic significance. METHODS: Blood samples were collected from 32 patients with stage IA LUAD and 31 healthy controls. GPR56 and perforin were analysed in circulating T-cell subsets by flow cytometry. In addition, a correlation between perforin and GPR56 expression was detected. Changes in GPR56+ cells in early LUAD patients were analysed, and the diagnostic significance of GPR56+ T cells for early LUAD was studied by receiver operating characteristic (ROC) curve analysis. RESULTS: The expression of GPR56 in CD8+ T cells from early-stage LUAD patients was significantly greater than that in CD4+ T cells. The percentage of perforin-positive GPR56+ cells in early-stage LUAD patients was high. GPR56 levels in the T cells of LUAD patients were significantly lower than those in healthy controls. ROC analysis revealed that the area under the curve for the percentage of GPR56-positive CD8+ TEMRA cells to distinguish early-stage LUAD patients from healthy individuals- reached 0.7978. CONCLUSION: The decreased expression of GPR56 in the peripheral blood of early-stage LUAD patients correlated with perforin levels, reflecting compromised antitumor immunity and aiding early-stage LUAD screening.

Alterations in Helios+ T cell subsets in peripheral blood of early-stage lung adenocarcinoma patients: Implications for early diagnosis.

OBJECTIVE: This study aimed to investigate the changes and significance of circulating Helios-associated T cell subsets in patients with early-stage lung adenocarcinoma (LUAD). METHODS: Blood samples were collected from 35 healthy controls and 34 patients with early-stage LUAD. Flow cytometry was used to analyze various CD4+ T cell subsets, including regulatory T(Treg) cells, follicular regulatory T(Tfr) cells, follicular helper T (Tfh) cells, and conventional T (con-T) cells. Correlation analysis was conducted to investigate the association of Helios-related subsets with clinical indicators. The ROC curve was used to explore the potential clinical value of Helios+ T cell subsets in the screening of patients with early LUAD. Fifteen of these patients were tracked after lung cancer resection and changes in Helios+ T cell subsets before and after treatment were analyzed. RESULTS: The percentage and absolute number of Tregs were up-regulated in LUAD patients while Tfh and con-T cells expressing Helios were down-regulated. Absolute counts of Tfr and con-T cells and Helios expression in Tfr and Treg decreased significantly after resection. Helios+ Tfh and con-T were negatively correlated with certain tumor markers. Areas under the curve (AUCs) of percentages and absolute counts of Helios+ Tfh, Treg, Tfr and con-T cells to distinguish early LUAD from healthy individuals were 0.7277, 0.5697, 0.5718, 0.7210 (percentages), 0.7336, 0.7378, 0.5908 and 0.7445(absolute numbers), respectively. CONCLUSION: Helios+ T cell subsets in peripheral blood of early-stage LUAD patients has changed significantly, which may be related to the pathogenesis of LUAD and could help for early diagnosis of LUAD.