Peripheral Blood Lymphocyte Subsets Research Articles

Establishment and evaluation of a risk prediction model for coronary heart disease in primary Sjögren’s syndrome based on peripheral blood IL-6 and Treg percentages

ObjectiveThis study aims to establish and evaluate a risk prediction model for coronary heart disease (CHD) in patients with primary Sjögren’s syndrome (pSS) based on peripheral blood levels of interleukin-6 (IL-6) and the percentage of regulatory T cells (Treg%). This model is intended to facilitate the timely identification of high-risk patients and the implementation of preventive measures.MethodsClinical data were collected from 120 pSS patients who visited the Second Hospital of Shanxi Medical University between November 2021 and September 2023. Patients were classified into pSS and pSS-CHD groups according to CHD diagnostic criteria. Peripheral blood lymphocyte subsets and cytokine levels were assessed using flow cytometry. Univariate and multivariate logistic regression analyses were employed to identify independent risk factors, and a nomogram was constructed based on these factors. The model’s discriminatory ability, calibration, and clinical utility were evaluated using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis.ResultsThe univariate and multivariate logistic regression analyses identified several independent risk factors for CHD in pSS patients: erythrocyte sedimentation rate (ESR) (OR=1.10, P=0.019), triglycerides (TG) (OR=3.67, P=0.041), IL-6 (OR=1.29, P=0.048), and Treg% (OR=0.25, P=0.004). A nomogram incorporating these factors demonstrated an area under the curve (AUC) of 0.96, indicating excellent predictive performance, and showed good calibration (P=0.599), suggesting significant clinical applicability. Furthermore, Treg% exhibited a negative correlation with cholesterol (CHOL) and low-density lipoprotein cholesterol (LDL-C) levels, while IL-6 showed a positive correlation with CHOL and LDL-C levels. TG was positively correlated with C-reactive protein (CRP).ConclusionThis study successfully developed a risk prediction model based on peripheral blood IL-6 and Treg% levels, providing critical evidence for the early identification and personalized prevention of CHD in pSS patients, with potential clinical implications.

Immune Signatures of Solid Tumor Patients Treated With Immune Checkpoint Inhibitors: An Observational Study.

Our study aimed to comprehensively describe the features of peripheral blood multiple immune cell phenotypes in solid tumor patients during pretreatment and after immunotherapy, providing a more convenient approach for studying the prognosis of immunotherapy in different solid tumor patients. We prospectively recruited patients with advanced solid tumors from Peking Union Medical College Hospital (PUMCH) between February 2023 and April 2024. Using multicolor flow cytometry, our study comprehensively observed and described the signatures of peripheral blood lymphocyte subsets including activation, proliferation, function, naïve memory, and T cell exhaustion immune cell subsets in this population of pretreatment and after immunotherapy. Our study enrolled 59 advanced solid tumor patients with immunotherapy and 59 healthy controls were matched by age and gender. The results demonstrated a marked upregulation in the expression of lymphocyte activation markers CD38 and HLA-DR, as well as exhaustion and proliferation markers PD-1 and Ki67, in solid tumor patients compared to healthy controls. After immune checkpoint blockade (ICB) treatment, mainly the expression of Ki67CD4+T and HLA-DRCD38CD4+T, was significantly upregulated compared to pretreatment levels (p = 0.017, p = 0.019, respectively). We further found that gynecological tumors with better prognoses had higher baseline activation levels of CD4+ T cells compared to other solid tumors with poorer prognoses. Our study elucidated the characteristics of different lymphocyte subsets in the peripheral blood of solid tumor patients. Further research revealed changes in the phenotypes of different lymphocyte subsets after ICIs treatment, with the activated phenotype of CD4+ T cells playing a crucial role in the antitumor effect. This lays the groundwork for further exploration of prognostic biomarkers and predictive models for cancer patients with immunotherapy.

The diagnostic value of peripheral blood lymphocyte testing in children with infectious mononucleosis

ObjectiveTo investigate the diagnostic value of peripheral blood lymphocyte testing in children with infectious mononucleosis (IM).MethodsA total of 135 children with IM as the IM group and 100 healthy volunteers as the healthy group were included in this retrospective study. Peripheral blood lymphocyte subsets marked as CD3+, CD4+, CD8+, CD16 + CD56+, and CD19 + in the peripheral blood were quantified using flow cytometry. Statistical analysis was performed using the chi-square test, Kruskal-Wallis test, AUROC curve, and Kappa consistency test to assess the diagnostic value of these markers in IM.ResultsThe AUROC curve for CD8 + cells and for CD4+/CD8 + ratios both achieved a value of 1 with the sensitivity and specificity of 100% (P<0.001). The Kappa coefficients were 1 for CD8+, CD4+/CD8 + ratios and the combined EBV analysis, indicating a 100% consistency with the clinical diagnosis. Significant differences were also observed in the CD3+, CD4+, CD16 + CD56+, and CD19 + lymphocyte subsets between the IM group and the healthy group (P<0.05).ConclusionThe evaluation of CD8 + and CD4+/CD8 + ratios in peripheral blood lymphocytes represents a significant advancement in the diagnosis of IM. Peripheral blood lymphocyte testing offers a reliable, sensitive, and specific diagnostic tool to enhance the clinical management of children with IM.

Evaluating peripheral blood lymphocyte subset composition and lipopolysaccharide-induced cytokine secretory activity in mononuclear leukocyte cultures from patients with febrile and meningeal forms of tick-borne encephalitis

Introduction.Multiple studies on immune response in patients with various clinical forms of tick-borne encephalitis (TBE) have shown conflicting results. The study aim was to estimate the changes in peripheral blood lymphocyte subset counts and activity of spontaneous and lipopolysaccharide (LPS)-stimulated cytokine production in the mononuclear leukocyte cultures in patients with febrile and meningeal acute TBE.Materials and methods.Groups 1 and 2 included 16 and 12 patients with febrile and meningeal acute TBE, respectively. The control group included 13 healthy donors. Hemogram and T-lymphocyte, T-helper cell, T-cytotoxic and NK cell counts were analyzed by flow cytometry at week 1 of the disease as well as the spontaneous and LPS-stimulated secretion levels of TNFα, IL-1β, IL-6, IL-10, IL-8, and MCP-1 were assessed by ELISA in the supernatants of mononuclear cell cultures twice: during hospitalization and two weeks later. Statistical analysis was performed by the Mann–Whitney U-test, and Wilcoxon test.Results.Group 2 demonstrated significant decrease in spontaneous and/or LPS-stimulated levels of proinflammatory cytokines IL-1β, IL-6, MCP-1, and TNFα, but showed higher IL-8 level as compared with Group 1. In addition, spontaneous and/or LPS-induced levels of IL-6 and TNFαin Group 2 did not significantly differ from the controls, which presumably also indicated the suppression of their production. In contrast, spontaneous and/or LPS-induced levels of IL-1β, IL-6, MCP-1, and TNFαin Group 1 were higher than in the controls. The spontaneous IL-10 level in the patients from both groups were higher than in the controls. Peripheral blood lymphocyte and T-cytotoxic T-lymphocyte counts in both groups of TBE patients were lower than in the controls. There was significant increase in neutrophil counts, decrease in NK cell count in Group 2 as compared to the patients with a milder febrile form.Conclusion.Meningeal acute TBE patients was presumably associated with inadequate immune response with NK cell deficiency, T-cell dysfunction, increased neutrophil count in the peripheral blood and impaired pro-inflammatory cytokine production related to innate immune response.

Comparative analysis of non-tuberculous mycobacterial lung disease and lung colonization: a case-control study

BackgroundNon-tuberculous mycobacteria (NTM) are common opportunistic pathogens, and the most common infection site is lung. NTM are found commonly in the environment. Many patients have NTM lung colonization (NTM-Col). NTM lung disease (NTM-LD) have no specific sympotms, though it is hard to differentiate NTM-LD and NTM-Col under this circumstance. The aim of this study is to explore the differences between NTM-LD and NTM-Col for future clinical diagnosis and treatment.MethodsWe retrospectively enrolled patients who had a history of NTM isolated from respiratory specimens in Peking Union Medical College Hospital (PUMCH) from January 1st, 2013 to December 31st, 2022. Patients were classified into NTM-LD group and NTM-Col group. Demographic characteristics, clinical manifestations, laboratory tests and imaging findings of the two groups were compared. Comparative analysis was also performed in peripheral blood lymphocyte subsets among three groups.ResultsA total of 127 NTM-LD patients and 37 NTM-Col patients were enrolled. Proportion of patients with bronchiectasis was higher in NTM-LD group than in NTM-Col group (P = 0.026). Predominant NTM isolates were Mycobacterium avium complex (MAC). NTM-LD group had a higher proportion of Mycobacterium intracellulare (P = 0.004). CD4+ T cells counts was lower in NTM-LD group (P = 0.041) than in NTM-Col group. Imaging finding of bronchiectasis (P = 0.006) was higher in NTM-LD group than in NTM-Col group. Imaging findings of bronchiectasis (OR = 6.282, P = 0.016), and CD4+ T cell count (OR = 0.997, P = 0.012) were independent associated factors for differential diagnosis between NTM-LD and NTM-Col.ConclusionNTM isolates from both NTM-LD and NTM-Col patients were predominantly MAC, with a higher Mycobacterium intracellulare isolation rate in NTM-LD group. Imaging findings of bronchiectasis and lower peripheral blood CD4+ T cell count may be helpful to separate the diagnosis of NTM-LD from NTM-Col.

High expression of CD3+T-lymphocytes in cerebrospinal fluid increases the risk of critical cerebral hemorrhage with systemic inflammatory response syndrome (SIRS) after surgery

ObjectiveTo assess the frequency of lymphocyte subsets and other laboratory indicators in paired cerebrospinal fluid (CSF) and peripheral blood (PB) samples from critically ill patients with intracerebral hemorrhage (ICH) who developed systemic inflammatory response syndrome (SIRS) following surgery. IntroductionNeuroinflammation and systemic inflammatory responses significantly contribute to secondary brain injury following ICH. Post-surgery SIRS is known to worsen clinical outcomes in ICH patients; however, the immune response in the CSF and PB has not been fully characterized. Understanding immunological changes in ICH patients with SIRS could lead to improved clinical management and prognostic outcomes. MethodsThis study involved a retrospective analysis of data from patients with ICH who underwent surgery in the Neurological Intensive Care Unit (NICU) of Baoding No. 1 Hospital, Hebei Province, China, between January and July 2022. Patients were divided into SIRS and non-SIRS groups based on the clinical criteria. Demographic, clinical, and laboratory data, including lymphocyte subsets in CSF and PB, were collected and analyzed. This study compared lymphocyte subsets and other inflammatory markers between the SIRS and non-SIRS groups. ResultsPatients with SIRS demonstrated higher systolic blood pressure (SBP) at admission, worse 90-day prognoses, elevated inflammatory markers, increased levels of complement proteins C3 and C4, and lower levels of immunoglobulin G (IgG) compared to patients without SIRS. Between 3–6 days post-surgery, SIRS patients showed higher percentages of CD3+T cells, CD4+T cells, and CD4+/CD8+ ratios in the CSF than non-SIRS patients. CD3+T cell percentages in the CSF were consistently higher than those in the PB and were independent of PB levels. In contrast, CD3-CD16+CD56+ natural killer (NK) cell percentages were lower in patients with SIRS. No significant differences in PB lymphocyte subsets were found between the two groups. A high CSF CD3+T cell percentage (≥85.68 %) was identified as the strongest predictor of critical ICH with SIRS after surgery, with an appropriate use criterion (AUC) of 0.7742, sensitivity of 77.42 %, specificity of 76.19 %, and 95 % CI of 0.6655–0.8829 (P < 0.0001). ConclusionElevated levels of CD3+T lymphocytes in CSF are strongly associated with an increased risk of severe cerebral hemorrhage and SIRS following surgery. These findings suggest that monitoring CSF immune markers, particularly CD3+T lymphocytes, could serve as valuable predictors for the development of SIRS in critically ill ICH patients and inform post-surgical treatment strategies.

Electroacupuncture attenuates depressive-like behaviors in poststroke depression mice through promoting hippocampal neurogenesis and inhibiting TLR4/NF-κB/NLRP3 signaling pathway.

The aim of this study was to investigate the impact and underlying molecular mechanisms of electroacupuncture on mice with poststroke depression (PSD). Mice were randomly allocated into sham, PSD, and electroacupuncture groups. Mice in the PSD and electroacupuncture groups underwent middle cerebral artery occlusion (MCAO) surgery following with sedentary behavior. Electroacupuncture targeting Zusanli (ST36) acupoint was performed 24 h after MCAO for 4 weeks in electroacupuncture group. The sucrose preference test, forced swimming test, open field test, tail suspension test, elevated plus maze, Catwalk analysis, RNA sequencing, Nissl staining, Golgi staining, TUNEL staining, Edu labeling, and doublecortin staining were performed. Lymphocyte subsets in peripheral blood and the levels of IL-1β, IL-6, TNF-α, and expression of Iba1/CD86, Iba1/NLRP3, TLR4/p38/NF-κB/NLRP3 pathways in the hippocampus were detected. Electroacupuncture effectively protected against the development of depression-like symptoms. The number of granulosa cells and doublecortin-positive cells in the dentate gyrus (DG) were significantly decreased in PSD group, which were significantly upregulated ( P < 0.01) by electroacupuncture. Electroacupuncture also significantly reduced ( P < 0.05) TUNEL-positive cells in the DG and CA1. RNA-seq revealed that electroacupuncture may exert antidepressant effect by regulating the inflammation mediated by TLR4/NF-κB/NLRP3 pathway in hippocampus. Electroacupuncture remarkably elevated ( P < 0.01) the ratio of CD4+ to CD8+ T cells and percentage of CD3-CD49b+ cells in CD45+CD49b+ cells in the peripheral blood. Electroacupuncture significantly reduced ( P < 0.05) the high levels of IL-1β, IL-6, TNF-α, iba1, TLR4, p-p38, p-NF-κB, and NLRP3 and sedentary behavior. Electroacupuncture was observed to mitigate depression symptoms and increase hippocampal neurogenesis in mice with PSD, possibly by inhibiting TLR4/p38/NF-κB/NLRP3 pathways and improving the microglia-mediated inflammatory microenvironment in the hippocampus.

EP.13D.05 Predictive Impact of Peripheral Blood Lymphocyte Subsets and Serum Markers in First-Line Immunotherapy for ES-SCLC—A Real-World Study

EP.13D.05 Predictive Impact of Peripheral Blood Lymphocyte Subsets and Serum Markers in First-Line Immunotherapy for ES-SCLC—A Real-World Study

Peripheral NK cell count predicts response and prognosis in breast cancer patients underwent neoadjuvant chemotherapy.

The count of lymphocyte subsets in blood can reflect the immune status of the body which is closely related to the tumor immune microenvironment and the efficacy of NAT. This study aims to explore the relationship between peripheral blood lymphocyte subsets and the efficacy and prognosis of NAT in breast cancer. We retrospectively analyzed clinicopathological information and peripheral blood lymphocyte subpopulation counts of patients receiving NAT from January 2015 to November 2021 at Sun Yat-sen University Cancer Center. Kaplan-Meier curves were used to estimate the survival probability. The independent predictors of NAT response and survival prognosis were respectively analyzed by multivariate logistic regression and Cox regression, and nomograms were constructed accordingly. The prediction efficiency of three nomograms was validated separately in the training cohort and the testing cohort. 230 patients were included in the study, consisting of 161 in the training cohort and 69 in the testing cohort. After a median follow-up of 1238 days, patients with higher NK cell value showed higher pCR rates and higher OS and RFS after NAT (all P < 0.001). Multivariate analyses suggested NK cell count was an independent predictor of NAT response, OS and RFS. We then built nomograms accordingly and validated the prediction performance in the testing cohort (C index for NAT response: 0.786; for OS: 0.877, for RFS: 0.794). Peripheral blood NK cell count is a potential predictive marker for BC patients receiving NAT. Nomograms based on it might help predict NAT response and prognosis in BC.

The correlation of GluR3B antibody with T lymphocyte subsets and inflammatory factors and their role in the progression of epilepsy

ObjectiveTo investigate changes in proportions of peripheral blood lymphocyte subsets, the correlation between the lymphocyte subsets and cytokine levels in patients with GluR3B antibody-positive epilepsy, analyze the role of GluR3B antibodies and cytokines in the progression of epilepsy. In addition, the immunotherapeutic effect in patients with GluR3B antibody-positive epilepsy will be evaluated.MethodsPatients with epilepsy hospitalized in the Department of Neurology of the affiliated Hospital of Xuzhou Medical University from December 2016 to May 2023 were recruited. GluR3B antibody levels were measured by enzyme-linked immunosorbent assay (ELISA). Lymphocyte subset proportions were determined using flow cytometry, and serum concentrations of 12 cytokines were measured using cytometric beads array. Differences in T lymphocyte subsets and inflammatory factors were analysed between GluR3B antibody positive and negative patients. Structural equation modeling (SEM) was used to analyse the role of GluR3B antibodies and inflammatory factors in drug-resistant epilepsy (DRE). Finally, the therapeutic effect of immunotherapy on epilepsy patients with GluR3B antibodies was assessed.ResultsIn this study, sixty-four cases of DRE, sixty-six cases of drug-naïve epilepsy (DNE), and forty-one cases of drug-responsive epilepsy were recruited. (1) DRE patients with positive GluR3B antibody were characterized by a significant increase in the proportion of cluster of differentiation (CD)4+ T lymphocytes, a decrease in CD8+ T lymphocytes, and an increase of CD4+/CD8+ ratio. Similar alterations in T lymphocyte subsets were observed in GluR3B antibody-positive patients with DNE. GluR3B antibody levels correlated positively with CD4+ T lymphocytes (r = 0.23) and negatively with CD8+ T lymphocytes (r=-0.18). (2) In patients with DRE, the serum concentrations of interleukin-1β (IL-1β), IL-8, and interferon-gamma (IFN-γ) were significantly higher in those with positive GluR3B antibody compared to those with negative GluR3B antibody. Serum IL-1β levels were also higher in GluR3B antibody-positive DNE patients compared to antibody-negative DNE patients. In drug-responsive epilepsy patients with GluR3B antibody-positive, both serum IL-1β and IFN-γ levels were higher than those with GluR3B antibody-negative. Moreover, the concentrations of serum GluR3B antibody were positively correlated with the levels of IL-1β, IL-8, and IFN-γ. (3) SEM analysis indicated that GluR3B antibody may be a direct risk factor for DRE (direct effect = 4.479, 95%CI 0.409–8.503), or may be involved in DRE progression through affecting IFN-γ and IL-8 levels (total indirect effect = 5.101, 95%CI 1.756–8.818). (4) Immunotherapy significantly decreased seizure frequency and serum GluR3B antibody levels, and the seizure frequency was positively correlated with the levels of GluR3B antibody levels in patients receiving immunotherapy.ConclusionsThis study demonstrates that GluR3B antibody may influence the progression of epilepsy through altering the proportion of CD4+ and CD8+ lymphocyte subsets and increasing proinflammatory cytokines. The seizure suppression of immunotherapy is associated with the decrease of GluR3B antibody levels. Thus, the present study contributes to a better understanding of the immunoregulatory mechanisms of autoimmune-associated epilepsy and provides a potential target for DRE.

Iron overload impact on peripheral blood cells, lymphocytes and karyotypes in newly diagnosed myelodysplastic syndromes (MDS) patients: a single-center retrospective analysis

We conducted a retrospective analysis of 68 newly diagnosed myelodysplastic syndrome (MDS) patients who were treated in the Department of Hematology at Yuncheng Central Hospital affiliated to Shanxi Medical University from October 2017 to March 2022. Based on the serum ferritin (SF) level, the newly diagnosed MDS patients were divided into two groups: iron overload (IOL) group (SF > 1000 ng/mL) and non-iron overload (NIOL) group(SF ≤ 1000 ng/mL). General clinical data, peripheral blood cells, lymphocyte subsets and marrow karyotypes were compared. We found that MDS patients with IOL had lower hemoglobin (Hb), lower reticulocyte (RET) counts, and lower absolute natural killer (NK) cell counts compared with NIOL group (p < 0.05). The correlation analysis also showed a negative correlation between the NK cell counts and SF level (r = −0.270, P = 0.026). Furthermore, we found IOL group had higher incidence of complex and poor karyotypes. In conclusion, we found that IOL is correlated with anemia in MDS patients, which may lead to a decrease in T lymphocyte cells, especially in NK cells, that play a role in the immune pathogenesis of MDS, thereby suppressing immune surveillance function. Additionally, IOL may contribute to the pathogenesis of MDS by affecting karyotypes.

Efficacy and safety of camrelizumab combined with chemotherapy in the treatment of advanced biliary malignancy and associations between peripheral blood lymphocyte subsets and clinical outcomes.

Biliary tract cancer (BTC) is a highly heterogeneous aggressive tumor, and advanced patients have poor prognosis. This work aimed to evaluate the efficacy and safety of camrelizumab combined with chemotherapy in treating advanced BTC, and to explore predictive biomarkers for distinguishing effective population. 183 advanced BTC patients admitted from September 2018 to September 2021 were retrospectively selected. 93 patients were treated with camrelizumab combined with chemotherapy (C+C group) and 90 patients were treated with chemotherapy alone (C group). Objective response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS), and median overall survival (mOS) were analyzed between two groups. Peripheral blood lymphocyte subsets were assessed by flow cytometry pre- and post-treatment. The mPFS (6.9 months) and mOS (12.1 months) in the C+C group were significantly longer than those in the C group, which were 5.2 months and 9.8 months respectively (HR 0.46, 95% CI 0.38-0.54, p=0.017; HR 0.39, 95% CI 0.32-0.47, p=0.033). The percentage of Total T, CD4+T, natural killer (NK) cells, lymphocyte, and CD4+/CD8+ cell ratios were significantly increased in effective patients after C+C treatment, but didn't increase in progressive disease (PD) patients. Higher percentage of Total T, CD4+T, and higher CD4+/CD8+ cell ratios post-treatment were associated with longer OS. Camrelizumab combining chemotherapy significantly prolonged the mPFS and mOS of advanced BTC patients. Immunotherapy may improve the immune status of advanced patients, and immunotherapy efficacy might be predicted based on the peripheral blood lymphocyte subsets.

Overexpression of serum HMGB1 and IDO in esophageal squamous cell carcinoma patients: potential clinical auxiliary diagnostic markers and immunotherapeutic targets.

High mobility group box 1 (HMGB1) and indoleamino-2, 3-dioxygenase (IDO) participate in the occurrence and development of esophageal squamous cell carcinoma (ESCC), regulate the tumor immune microenvironment, and are closely related to tumor growth and metastasis. However, the regulatory mechanism of serum HMGB1 and IDO has not been clarified and needs further exploration. Blood samples of 55 ESCC patients initially hospitalized in the Fourth Hospital of Hebei Medical University from August 2021 to January 2022 were selected as the ESCC group, and relevant clinical data were collected, and blood samples from 40 healthy people during the same period were selected as the control group. Serum HMGB1 and IDO levels were determined by ELISA, and lymphocyte subsets in peripheral blood of all subjects were detected by flow cytometry. The correlation between the expression levels of HMGB1 and IDO in ESCC cells was detected by Western blot. Serum HMGB1 and IDO levels were significantly increased in ESCC patients, and with the progression of ESCC patients, serum HMGB1 and IDO levels were also gradually increased; serum HMGB1 was significantly correlated with IDO; serum HMGB1 and IDO combined with CEA and SCC-Ag were of high value in predicting the clinical progression of ESCC patients; the absolute counts of CD4+CD28+T cells and CD8+CD28+T cells in high HMGB1 group were significantly lower than those in low HMGB1 group, while the percentage of CD4+PD-1+T cells was significantly higher than that in low HMGB1 group; the percentage and absolute counts of CD4+CD28+T cells and the absolute counts of CD8+CD28+T cells in high IDO group were significantly lower than those in the low IDO group, while the percentage of CD8+PD-1+T cells was significantly higher than that in the low IDO group; increased serum HMGB1 and IDO expression levels were closely related to poor prognosis in ESCC patients; and HMGB1 may promote IDO expression by activating NF-κB signaling pathway. Serum HMGB1 and IDO have a synergistic effect, they inhibit immune function and promote tumor progression in ESCC patients, and also lead to poor prognosis.

Expression of γδ T cells and lymphocyte subsets in newly diagnosed multiple myeloma patients

ObjectiveTo retrospectively analyze the expression and significance of γδ T cells and lymphocyte subsets in peripheral blood on patients with multiple myeloma (MM). MethodsFifty-five patients with multiple myeloma admitted to Yangpu Hospital Affiliated to Tongji University from January 2022 to August 2023 were selected as the disease group, and were categorized into stage I group, stage II group and stage III group according to the International Staging System (ISS) of multiple myeloma. All included patients were consecutive visits. Another 30 cases of healthy people with physical examination were selected as the control group. Flow cytometry was used to detect the γδ T cells and lymphocyte subsets in the peripheral blood of the subjects. After clinical indicators of patients and healthy controls were collected, the statistical analysis was conducted. ResultsCompared with the control group, the percentage of γδ T cells and CD8+ T cells in the disease group were higher, while, the absolute numbers of total peripheral blood lymphocytes (LYMT) and CD19+ B cells, percentage of CD19+ B cells, CD3+ T cells, CD4+ T cells were lower (P​<​0.05). The percentage of γδ T cells (P​<​0.001), the percentage of CD19+ B cells (P​=​0.003), the absolute number of CD3+ T cells (P​=​0.010), the absolute number of CD8+ T cells (P​=​0.002) were the significant influential factors of MM. γδ T cells (P​=​0.004), neutrophils (P​<​0.001), neutrophil to lymphocyte ratio (P​=​0.003), and white blood cell count (P​<​0.001) were statistically different in different stages. ROC curve suggested that the area under the curve of the percentage of γδ T cells in predicting the MM were 0.973 (P​<​0.001) which had certain diagnostic value. Conclusionsγδ T cells and lymphocyte subsets (CD8+ T cells, CD19+ B cells, CD3+ T cells, etc.) in patients with newly diagnosis of MM can reflect the immune function of the patient’s organism, which is a key factor of MM. γδ T cells influence the staging of MM patients, and also have certain diagnostic value.

Soluble MIC-A, IPI, and response to treatment strongly predict survival in patients with germinal center diffuse large B cell lymphoma.

To analyze lymphocyte subsets and sMIC-A in germinal center DLBCL. sMICA, sMICB, and peripheral blood lymphocyte subsets (CD4+, CD8+, NK, NKT, γδ T cells, and dendritic cells) were analyzed in 59 patients and 60 healthy donors. Patients had decreased numbers of type 1 and type 2 dendritic cells, NK, iNKT, CD4 T, and CD8 T cells, and higher levels of sMIC-A. The 2-year PFS for high IPI scores and high sMIC-A was 24% and 28%, respectively. The 2-year OS for high IPI scores and high sMIC-A was 42% and 33%. The 2-year PFS and OS for patients not achieving response to treatment were 0% and 10%, respectively. The MICPI score (one point each for high IPI score and high sMIC-A) showed that those patients summing two points had worse PSF and OS. Patients with DLBCL have decreased numbers of peripheral lymphocyte subsets and high levels of sMIC-A. The addition of sMIC-A to IPI could improve its prognostic relevance.

Impact of Chemotherapy on Circulating Lymphocyte Subsets in Lung Cancer Patients.

Lung cancer remains a leading cause of cancer-related death and chemotherapy stands as a fundamental component in therapy. Chemotherapy-induced myelosuppression encompasses a spectrum of hematological declines, including not only neutrophils but also lymphocytes, hemoglobin levels and platelets. This retrospective cohort study investigates alterations in peripheral blood lymphocyte subsets. By uncovering these changes, our goal is to refine patient management strategies, ensuring that the benefits of chemotherapy are maximized while minimizing its detrimental effects. We retrospectively analyzed 159 lung cancer patients. Patients were categorized as "NT" (n=108, no previous anti-tumor therapy), and "PT" (n=51, prior therapy followed by at least a two-month treatment-free interval). Post-chemotherapy, patients were reassessed and grouped into "EarlyCycle" for those who underwent four or fewer cycles, and "LateCycle" for those who underwent more than four cycles. The study focused on analyzing the percentages of lymphocyte subsets, including T cells (CD4+, CD8+), B cells, and natural killer (NK) cells, across these groups. For T cells, the EarlyCycle group exhibited a significant increase compared to NT (0.7783 vs 0.7271; p=0.0017) and PT (0.7783 vs 0.6804; p=1.6e-05). B cells showed a significant decrease from NT to LateCycle (0.1014 vs 0.0817; p=2.2e-05) and from PT to LateCycle (0.1317 vs 0.0817; p=6.2e-10). NK cells significantly decreased in the EarlyCycle group compared to NT (0.1109 vs 0.1462; p=0.00816) and PT (0.1109 vs 0.1513; p=0.00992), with no significant change in the LateCycle group compared to either NT or PT (p>0.05). Chemotherapy significantly affects lymphocyte subsets in a treatment-specific manner. The EarlyCycle group experienced a reduction in NK cell and an increase in T cell, suggesting a damage of innate immunity and an early shift towards adaptive immunity. The LateCycle group showed a substantial decrease in B cell, indicating a delayed effect on humoral immunity components.

Correlations of PSGL-1 VNTR polymorphism with the susceptibility to severe HFMD associated with EV-71 and the immune status after infection

Enterovirus 71 (EV-71) has strong neurotropism, and it is the main pathogen causing severe hand, foot, and mouth disease (HFMD). In clinical observations, significant differences were observed in the severity and prognosis of HFMD among children who were also infected with EV-71. Genetic differences among individuals could be one of the important causes of differences in susceptibility to EV-71–induced HFMD. As P-selectin glycoprotein ligand-1 (PSGL-1) is an important receptor of EV-71, the correlation between single-nucleotide polymorphisms (SNPs) in PSGL-1 and the susceptibility to severe HFMD following EV-71 infection is worth studying. Given the role of PSGL-1 in immunity, the correlations between PSGL-1 SNPs and the immune status after EV-71 infection are also worth studying. Meanwhile, PSGL-1 variable number of tandem repeats (VNTR) represents a research hotspot in cardiovascular and cerebrovascular diseases, but PSGL-1 VNTR polymorphism has not been investigated in HFMD caused by EV-71 infection. In this study, specific gene fragments were amplified by polymerase chain reaction, and PSGL-1 VNTR sequences were genotyped using an automatic nucleic acid analyzer. The correlations of PSGL-1 VNTR polymorphism with the susceptibility to EV-71–associated severe HFMD and the post-infection immune status were analyzed. The PSGL-1 VNTR A allele was identified as a susceptible SNP for severe HFMD. The risk of severe HFMD was higher for AA + AB genotype carriers than for BB genotype carriers. The counts of peripheral blood lymphocyte subsets were lower in AA + AB genotype carries than in BB genotype carries. In conclusion, PSGL-1 VNTR polymorphism is associated with the susceptibility to EV-71–induced severe HFMD and the immune status after infection. PSGL-1 VNTR might play a certain role in the pathogenesis of severe cases.

Exploratory study of PD-1 inhibitors for recurrent meningioma.

26 Background: Meningiomas are the most common primary intracranial tumor. Some patients still have poorly controlled conditions after multiple surgeries and radiotherapies. More effective treatment methods are urgently needed. Previous studies have suggested that meningioma may shape an inhibitory tumor immune microenvironment and achieve immune escape by expressing programmed cell death ligand 1 (PD-L1) and other factors. Immune checkpoint inhibitors (ICIs) such as PD-1 inhibitors have shown promising efficacy in cases, but large-sample studies are needed to confirm these findings. Methods: Recurrent meningioma patients were included and treated with PD-1 inhibitors until tumor progression or intolerance occurred. The efficacy evaluation of enrolled patients used the Response Assessment in Neuro-Oncology (RANO) criteria. The primary endpoint was progression-free survival at 6 months (PFS-6), and secondary endpoints were progression-free survival at 12 months (PFS-12) and overall survival (OS). Adverse events were also recorded. Regular imaging follow-ups were conducted, and clinical characteristics were collected for survival analysis. Peripheral blood lymphocyte subsets and cytokines were detected before and after treatment, and tumor paraffin sections were used for immunohistochemical detection of relevant molecular markers. Results: A total of 35 recurrent meningioma patients (10 grade I, 14 grade II, 11 grade III) were included. Among all grades of patients, the median PFS was 9 months, PFS-6 was 63.6%, and PFS-12 was 47.6%. In grade I patients, the median PFS was 14 months, PFS-6 was 83%, and PFS-12 was 67%. In grade II/III patients, the median PFS was 9 months, PFS-6 was 58.9%, and PFS-12 was 42%. Among all grades of meningioma patients, PFS was significantly correlated with Ki-67 index (P = 0.021) and tumor progression times (P = 0.019). In grade II/III meningioma patients, PFS was only correlated with tumor progression times (P = 0.012). Twenty-five patients had stable disease, and seven patients had disease progression, with no patient achieving partial or complete remission. There was no significant correlation between tumor mutation burden (TMB) and PFS. Further immunohistochemical analysis of tumor tissues in three recurrent high-grade patients revealed varying degrees of increase in local CD3+, CD4+, CD8+ and PD-1+ T lymphocytes after treatment compared to baseline. Conclusions: Our study suggests that PD-1 inhibitors may prolong PFS in recurrent meningioma patients (especially high-grade) with good drug safety, warranting further exploration. Recurrent meningiomas have an immunosuppressive tumor microenvironment, and PD-1 inhibitors may improve the immune status of tumor microenvironments. Clinical trial information: NCT04728568 .

Impact of peripheral lymphocyte subsets on prognosis for patients after acute ischemic stroke: A potential disease prediction model approach.

To investigate the relationship between peripheral blood lymphocyte subsets and prognosis in patients with acute ischemic stroke (AIS). We enrolled 294 patients with AIS and collected peripheral blood samples for analysis of lymphocyte subsets. Prognosis was assessed at 3 months using the modified Rankin Scale (mRS). Association between lymphocyte count and poor outcomes (mRS score >2) was assessed using logistic regression. Individualized prediction models were developed to predict poor outcomes. Patients in the mRS score ≤2 group had higher T-cell percentage (odds ratio [OR] = 0.947; 95% confidence interval [CI]: 0.899-0.998; p = 0.040), CD3+ T-cell count (OR = 0.999; 95% CI: 0.998-1.000; p = 0.018), and CD4+ T-cell count (OR = 0.998; 95% CI: 0.997-1.000; p = 0.030) than those in the mRS score >2 group 1-3 days after stroke. The prediction model for poor prognosis based on the CD4+ T-cell count showed good discrimination (area under the curve of 0.844), calibration (p > 0.05), and clinical utility. Lower T cell percentage, CD3+, and CD4+ T-cell counts 1-3 days after stroke were independently associated with increased risk of poor prognosis. Individualized predictive model of poor prognosis based on CD4+ T-cell count have good accuracy and may predict disease prognosis.

A novel long noncoding RNA ENST00000597482 serves as a potential biomarker for disease activity and diagnosis of systemic lupus erythematosus.

Emerging evidence indicate that long noncoding RNAs (lncRNAs) may play an important role in the pathogenesis of systemic lupus erythematosus (SLE) however, the contribution of lncRNAs to SLE remains largely unclear. Our study aimed to explore the lncRNA expression profiles in peripheral blood mononuclear cells (PBMCs) from SLE patients. LncRNA sequencing was used to detect differentially expressed genes in PBMCs from 5 SLE-MIX samples and 3 healthy controls (HC)-MIX samples, and the expression of selected lncRNAs was further verified by real-time quantitative polymerase chain reaction (RT‒qPCR). The correlation of lncRNA expression with laboratory indicators as well the SLE disease activity index 2000 (SLEDAI‒2K) score from 72 SLE patients was assessed by Spearman's test. The association between lncRNA ENST00000597482 and organ involvement in SLE patients was determined by the Mann‒Whitney U test. Moreover, lymphocyte subsets in peripheral blood from SLE patients were measured by flow cytometry. In addition, the diagnostic value of lncRNAs in predicting SLE was evaluated by receiver operating characteristic (ROC) curve analysis. The lncRNA expression profiles demonstrated 218 differentially expressed lncRNAs, including 121 upregulated genes and 97 downregulated genes, in PBMCs from SLE patients compared to HCs. Among the 10 candidate genes selected, only lncRNA ENST00000597482, which was lower in SLE PBMCs than in HCs, was consistent with the sequencing results. LncRNA ENST00000597482 expression was negatively correlated with SLEDAI-2K score and the titres of ANA antibodies and anti-double-stranded DNA (anti-dsDNA) antibodies. Of note, SLE patients with lower expression of lncRNA ENST00000597482 were prone to develop organ involvement. Furthermore, lncRNA ENST00000597482 exhibited potential diagnostic value in differentiating SLE patients from HCs. LncRNA ENST00000597482 expression was lower in PBMCs from SLE patients than HCs and was negatively correlated with the SLEDAI-2K score and autoantibody titres. In addition, lncRNA ENST00000597482 could act as a novel biomarker for disease activity and diagnosis of SLE.