BMC Immunology最新文献

The reconstruction of clonal families (CFs) in B-cell receptor (BCR) repertoire analysis is a crucial step to understand the adaptive immune system and how it responds to antigens. The BCR repertoire of an individual is formed throughout life and is diverse due to several factors such as gene recombination and somatic hypermutation. The use of Adaptive Immune Receptor Repertoire sequencing (AIRR-seq) using next generation sequencing enabled the generation of full BCR repertoires that also include rare CFs. The reconstruction of CFs from AIRR-seq data is challenging and several approaches have been developed to solve this problem. Currently, most methods use the heavy chain (HC) only, as it is more variable than the light chain (LC). CF reconstruction options include the definition of appropriate sequence similarity measures, the use of shared mutations among sequences, and the possibility of reconstruction without preliminary clustering based on V- and J-gene annotation. In this study, we aimed to systematically evaluate different approaches for CF reconstruction and to determine their impact on various outcome measures such as the number of CFs derived, the size of the CFs, and the accuracy of the reconstruction. The methods were compared to each other and to a method that groups sequences based on identical junction sequences and another method that only determines subclones. We found that after accounting for data set variability, in particular sequencing depth and mutation load, the reconstruction approach has an impact on part of the outcome measures, including the number of CFs. Simulations indicate that unique junctions and subclones should not be used as substitutes for CF and that more complex methods do not outperform simpler methods. Also, we conclude that different approaches differ in their ability to correctly reconstruct CFs when not considering the LC and to identify shared CFs. The results showed the effect of different approaches on the reconstruction of CFs and highlighted the importance of choosing an appropriate method.

Background: Imbalanced immune responses are involved in developing preeclampsia (PE). We wish to explore the expression and potential changes of immune checkpoint molecules TIGIT, CD226 and CD155 in PE patients.

Methods: The expression of the immune checkpoint molecules TIGIT, CD226 and CD155 in different lymphocyte subpopulations was determined by flow cytometry in 24 patients with PE and compared to 24 healthy pregnant women of the same gestational age as the controls.​Serum CD155 was detected by ELISA in the patients with PE compared to controls.

Results: The percentages of CD4⁺ and CD8⁺ T lymphocytes in the peripheral blood of PE patients were not significantly different from those of the controls, whereas the regulatory T cells (Tregs) in PE patients were significantly lower than those in controls (6.43 ± 1.77% vs. 7.48 ± 1.71%, P = 0.0420). The expression of TIGIT and CD226 showed different percentages on CD4⁺ T cells, CD8⁺ T cells and Treg cells. However, the difference in the percentages of TIGIT, CD226 on these T cells between the two groups was not statistically significant. The level of CD155 in peripheral serum of PE patients was 6.64 ± 1.79 ng/ml, which was not significantly different from that in the control group 5.61 ± 1.77 ng/ml, P = 0.0505. The present results demonstrate that TIGIT, CD226 and CD155 are not present at altered immune conditions in the peripheral blood of patients with PE, compared with normal pregnant women.

Conclusion: The immune checkpoint molecules TIGIT, CD226 and CD155 are not abnormally expressed in PE patients.

Purpose: The objective of this study was to identify potential predictors of immune-related adverse events (irAEs) in cancer patients receiving immune checkpoint inhibitor therapy among serum indexes, case data, and liquid biopsy results.

Methods: We retrospectively analyzed 418 patients treated with anti-programmed cell death 1(PD-1)/PD-1 ligand (PD-L1) inhibitors from January 2018 to May 2022 in our cancer center. We identified factors that correlated with the occurrence of irAEs and evaluated associations between irAEs and anti-PD-1/PD-L1 inhibitor responses.

Results: The incidence of irAEs was 42.1%, and pneumonitis (9.1%), thyroid toxicity (9.1%), cardiotoxicity (8.1%), and dermatologic toxicity (6.9%) were the four most common irAEs. Multivariate logistic analysis identified female sex, antibiotic use, higher post-treatment neutrophil-to-lymphocyte ratio (NLR), and higher baseline circulating tumor cell (CTC) level, as predictive biomarkers for the occurrence of irAEs. A lower baseline prognostic nutritional index (PNI), body mass index (BMI) ≥ 25 kg/m², and higher post-treatment lactate dehydrogenase (LDH) level were predictive factors for more severe irAEs (higher severity grade). Patients without irAEs had better overall survival than those with irAEs. Specifically, pneumonitis and cardiotoxicity were found to be significant predictors of poor prognosis in the irAE subgroup with different organ-related irAEs. Low-dose steroid (dexamethasone 10 mg) treatment had no significant effect on outcomes.

Conclusions: Gender, antibiotic use, post-treatment NLR, and baseline CTC level are potential predictive biomarkers of irAEs, while baseline PNI, BMI, and post-treatment LDH may predict the severity of irAEs. The predictive effect of irAE occurrence on survival benefit may depend on the type of irAE.

Immune cells, such as macrophages, B cells, neutrophils and T cell subsets, have been implicated in the context of obesity. However, the specific role of Th2 cells in adipose tissue function has remained elusive. Eight-week-old male CD3ε^─/─ mice were randomly divided into two groups (≥ 5 mice per group): one received intravenous injection of Th2 cells isolated from LAT^Y136F mice, while the other receiving PBS as a control. Both of groups were subjected to a high-fat diet (HFD). The adoptive transfer of polarized Th2 cells led to a significant reduction in obesity following a HFD. This reduction was accompanied by improvements in hepatic steatosis, glucose intolerance, and insulin resistance. Mechanistically, Th2 cell treatment promoted oxidative phosphorylation of adipocytes, thereby contributing to a reduction of lipid droplet accumulation. These findings suggest that Th2 cell therapy represents a novel approach for treating diet-induced obesity and other diseases involving lipid droplet accumulation disorders.