Peripheral Lymphocyte Subsets Research Articles

Heterogeneity in peripheral blood immune lymphocyte subsets predicts the response of immunotherapy or chemoradiotherapy in advanced lung cancer: an analysis across different pathological types, treatment modalities and age

Heterogeneity in peripheral blood immune lymphocyte subsets predicts the response of immunotherapy or chemoradiotherapy in advanced lung cancer: an analysis across different pathological types, treatment modalities and age

Dynamics of Peripheral Lymphocyte Subsets from Birth until Old Age

The immune system is inexperienced before birth and tends to be tolerogenic, rather than immunogenic. After birth, the adaptive immune system develops while facing microbial challenges, but it can become impaired as old age progresses and persistent inflammation can lead to chronic morbidity, disability and frailty. To investigate the potential contributions of lymphocyte subsets to immunity from birth until old age, we enumerated circulating innate and conventional lymphocytes and measured serum cytokine levels in 10 cord blood samples and in peripheral blood from 10 healthy term neonates, 23 healthy school-age children, 25 young adults and 11 older subjects. Flow cytometric analysis revealed that B cell frequencies increase during childhood and gradually decrease into adulthood, whereas natural killer cell frequencies increase throughout life. T cell frequencies remained relatively constant throughout life, as did their expression of CD4 and CD8. However, all four innate T cell populations studied—invariant natural killer T cells, mucosa-associated invariant T cells and the Vδ1 and the Vδ2 subsets of γδ T cells—were extremely rare in cord blood and in peripheral blood of neonates, but they expanded after birth reaching highest levels in adulthood. Analysis of serum cytokine levels revealed that proinflammatory and T helper type 1 (Th1) cytokine levels increase in adulthood, whereas Th2 and Th17 cytokine levels remain relatively constant. These changes in lymphocyte numbers and cytokine levels across the lifetime are likely to affect immunocompetence, leaving newborn and elderly people susceptible to infection, cancer and immune-mediated disease.

Alterations and clinical value of peripheral lymphocyte subsets and inflammatory factors in paragangliomas.

Given the pivotal role of immune and inflammatory responses in tumor patients, the present study aimed to explore alterations and the clinical value of peripheral lymphocyte subsets and inflammatory factors in pheochromocytomas/paragangliomas (PPGLs). The clinical data of 327 patients, including 102 patients with metastatic PPGLs, were retrospectively analysed. Peripheral lymphocyte subsets were determined by flow cytometry. Relationships between immune and inflammatory parameters and clinicopathological characteristics were evaluated by intergroup comparisons and correlation analyses. Univariate and multivariate logistic regression analyses were employed to identify metastatic indicators. The corresponding nomogram was constructed and evaluated for discrimination and calibration. The median age at diagnosis was 45.0 years, and duration of follow-up was 3.0 years. Compared with those in younger patients (<45.0 years), most lymphocyte subsets were significantly reduced in older patients (≥45 years) (P<0.05). The count of lymphocytes, CD3+T cells and CD4+T cells were negatively correlated with 24h-urinary epinephrine and plasma metanephrine levels (R=-0.2∼-0.1, P<0.05). In addition, patients with lymph node (n=37) or bone metastases (n=41) had a lower percentage of CD4+T cells (P<0.05). Multivariate analysis revealed that CD3+T cell≥1446.50/μl, CD4+T cell%<39.95%, CD8+T cell%<24.95%, CD4+/CD8+T cell ratio<2.88, B cell%≥8.65%, TNF-alpha<12.45pg/ml, IL8<30.50pg/ml and PLT≥269.50*109/L were significant indicators of metastatic PPGLs. The area under the curve (AUC) of the nomogram was 0.800 (95% CI: 0.736-0.865). Immunesenescence, characterized by immune dysfunction with aging, was observed in PPGLs. Higher epinephrine and metanephrine levels might impair host's immune response. Monitoring changes in peripheral lymphocyte subsets and serum cytokines could indicate patients' conditions, especially the occurrence of metastasis.

Vitamin D Supplementation Selectively Affects Peripheral Lymphocyte Subsets in Infertile Women.

This study aimed to explore the effect of vitamin D supplementation on lymphocyte subsets in infertile women. The study involved a total of 247 patients who suffered recurrent embryo implantation failure (RIF) or recurrent spontaneous abortion (RSA) between January and December 2019 in the Reproductive Medicine Center of Children's Hospital of Shanxi and Women Health Center of Shanxi. The differences in the vitamin D and lymphocyte subsets of the two diseases, the correlation between the 25-hydroxy vitamin D and lymphocyte subsets, the changes in the lymphocyte subsets after vitamin D supplementation and the impact on pregnancy outcome were analysed. The prevalence of vitamin D deficiency was 77.33% (191/247). After vitamin D supplementation, there were no significant differences in helper T cells (Th), cytotoxic T cells (Tc), Th/Tc and natural killer cells (NK) (p > 0.05), but there were significant differences in leukocyte differentiation antigens 3+ (CD3+), natural killer T cells (NKT), B lymphocytes and vitamin D (p < 0.05). Before vitamin D supplementation, the difference in the composition ratio of different vitamin D levels between the RIF and RSA groups was not statistically significant. At different vitamin D levels, there were no significant differences in CD3+, Th, Tc, Th/Tc, NK or B lymphocyte (p > 0.05), but there was a significant difference in NKT (p < 0.05). Vitamin D supplementation can reduce the level of NKT in infertile women, which may be of benefit to the pregnancy outcome of couples who experience RIF.

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.

A predictive model for progression to clinical arthritis in at-risk individuals with arthralgia based on lymphocyte subsets and ACPA.

The presence of autoantibodies against citrullinated proteins (ACPA) significantly increases the risk of developing rheumatoid arthritis (RA). Dysregulation of lymphocyte subpopulations was previously described in RA. To propose the predictive model for progression to clinical arthritis based on peripheral lymphocyte subsets and ACPA in individuals who are at risk of RA. Our study included 207 at-risk individuals defined by the presence of arthralgias and either additional ACPA positivity or meeting the EULAR definition for clinically suspect arthralgia. For the construction of predictive models, 153 individuals with symptom duration ≥12 months who have not yet progressed to arthritis were included. The lymphocyte subsets were evaluated using flow cytometry and anti-CCP using ELISA. Out of all individuals with arthralgia, 41 progressed to arthritis. A logistic regression model with baseline peripheral blood lymphocyte subpopulations and ACPA as predictors was constructed. The resulting predictive model showed that high anti-CCP IgG, higher percentage of CD4+ T cells, and lower percentage of T and NK cells increased the probability of arthritis development. Moreover, the proposed classification decision tree showed, that individuals having both high anti-CCP IgG and low NK cells have the highest risk of developing arthritis. We propose a predictive model based on baseline levels of lymphocyte subpopulations and ACPA to identify individuals with arthralgia with the highest risk of progression to clinical arthritis. The final model includes T cells and NK cells, which are involved in the pathogenesis of RA. This preliminary model requires further validation in larger at-risk cohorts.

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.

Low Levels of Natural Killer Cell in Newly Diagnosed Myelodysplastic Syndromes Patients May Confer Poor Prognosis: A Retrospective Cohort Study.

Immune imbalance appears to have a critical role in tumor growth according to emerging research. Peripherallymphocyte subsets are considered to reflect the systemic immune response and clinical prognosis. The prognostic value of lymphocyte subpopulations in myelodysplastic syndrome (MDS) patients remains unclear. A total of 94 MDS patients were enrolled for the study. X-tile software was performed to determine the prognostic significance of various lymphocyte subpopulations, CD3, CD4, CD8, CD4/CD8 ratio, natural killer cell (NK) and CD19. Among them, the appropriate threshold of NK percent could be found only. Patients were divided into the high NK percent group and the low NK percent group. The prognostic significance was determined by univariate and multivariate Cox hazard models. MDS patients with lower NK level had significantly shorter overall survival (OS). Based on univariate analysis, male gender (P = 0.030), lower HB (<10 g/dl, P = 0.029), higher BM blast (>5%, P < 0.0001), higher-risk IPSS-R cytogenetic (P = 0.032) and lower NK percent (P < 0.0001) were significantly associated with shorter OS. Multivariate Cox proportional hazards regression analysis indicated that low NK was also independent adverse prognostic factor for OS in MDS. Decreased NK level predicts poor prognosis independent of the IPSS-R and provide a novel evaluation factor for MDS patients.

Analysis of peripheral lymphocyte subsets and T-cell exhaustion in SARS-CoV-2 Infection.

: Immune responses against Coronavirus (SARS-CoV-2) may be highly complex. It has been suggested that T-cell fatigue develops due to continuous stimulation of T-cells by SARS-CoV-2 in Coronavirus disease-2019 (COVID-19). It was aimed to assess peripheral lymphocyte subsets and T-cell exhaustion in various clinical courses of the disease in patients diagnosed with COVID-19. This study included 150 patients who were assigned into the "mild-to-moderate disease" group, or "severe disease" group based on their clinical and laboratory characteristics. Peripheral lymphocyte subsets and T-cell exhaustion markers [programmed cell death protein 1 (PD-1) and T-cell immunoglobulin and mucin-domain containing-3 (Tim-3)] were determined in the peripheral blood using flow cytometry. Mean (±SD) age was 53.3 ± 14.5 years, and female to male ratio was 55/95. In the mild-to-moderate disease (MMD) group, 55 patients had pneumonia and 20 patients had COVID-19 without pneumonia. In the severe disease (SD) group, 43 patients had severe pneumoniae and 32 patients were in critical condition. Lymphocyte counts were less than 1.0 x 109/L in 69.3% of the patients in the SD group, and the difference between the MMD group and SD group was statistically significant (p= 0.001). Total T cells, CD4+ and CD8+ T-cell counts were significantly lower in the SD group vs. MMD group (p< 0.001, p< 0.001, p< 0.001, respectively). PD-1 expression by CD8+ and CD4 T+ cells was higher (p= 0.042, p= 0.029, respectively) and Tim-3 expression from CD4 T+ cells was lower (p= 0.000) in the SD group vs. MMD group. Serum IFN-γ levels were not statistically different in the MMD and SD groups (p= 0.2). T-cell counts may be significantly reduced along with an increased expression of the T-cell exhaustion marker PD-1 in severe COVID-19, but Tim-3 expression was not increased in our study patients.

Lymphocyte profile in peripheral blood of patients with multiple myeloma.

Multiple myeloma (MM) is a disease which remains incurable. One of the main reasons is a weakened immune system that allows MM cells to survive. Therefore, the current research is focused on the study of immune system imbalance in MM to find the most effective immunotherapy strategies. Aiming to identify the key points of immune failure in MM patients, we analysed peripheral lymphocytes subsets from MM patients (n = 57) at various stages of the disease course and healthy individuals (HI, n = 15) focusing on T, NK, iNKT, B cells and NK-cell cytokines. Our analysis revealed that MM patients exhibited immune alterations in all studied immune subsets. Compared to HI, MM patients had a significantly lower proportion of CD4 + T cells (19.55% vs. 40.85%; p < 0.001) and CD4 + iNKT cells (18.8% vs. 40%; p < 0.001), within B cells an increased proportion of CD21LCD38L subset (4.5% vs. 0.4%; p < 0.01) and decreased level of memory cells (unswitched 6.1% vs. 14.7%; p < 0.001 and switched 7.8% vs. 11.2%; NS), NK cells displaying signs of activation and exhaustion characterised by a more than 2-fold increase in SLAMF7 MFI (p < 0.001), decreased expression of NKG2D (MFI) and NKp46 (%) on CD16 + 56 + and CD16 + 56- subset respectively (p < 0.05), Effective immunotherapy needs to consider these immune defects and monitoring of the immune status of MM patients is essential to define better interventions in the future.

Alterations in Peripheral Lymphocyte Subsets under Immunochemotherapy in Stage IV SCLC Patients: Th17 Cells as Potential Early Predictive Biomarker for Response.

UICC stage IV small-cell lung cancer (SCLC) is a highly aggressive malignancy without curative treatment options. Several randomized trials have demonstrated improved survival rates through the addition of checkpoint inhibitors to first-line platin-based chemotherapy. Consequently, a combination of chemo- and immunotherapy has become standard palliative treatment. However, no reliable predictive biomarkers for treatment response exist. Neither PD-L1 expression nor tumor mutational burden have proven to be effective predictive biomarkers. In this study, we compared the cellular immune statuses of SCLC patients to a healthy control cohort and investigated changes in peripheral blood B, T, and NK lymphocytes, as well as several of their respective subsets, during treatment with immunochemotherapy (ICT) using flow cytometry. Our findings revealed a significant decrease in B cells, while T cells showed a trend to increase throughout ICT. Notably, high levels of exhausted CD4+ and CD8+ cells, alongside NK subsets, increased significantly during treatment. Furthermore, we correlated decreases/increases in subsets after two cycles of ICT with survival. Specifically, a decrease in Th17 cells indicated a better overall survival. Based on these findings, we suggest conducting further investigation into Th17 cells as a potential early predictive biomarkers for response in patients receiving palliative ICT for stage IV SCLC.

Peripheral CD3+CD4+ T cells as indicators of disease activity in thyroid eye disease: age-dependent significance.

To provide an in-depth analysis of the association of peripheral lymphocytes and the disease activity of thyroid eye disease (TED). This retrospective study enrolled 65 active TED patients and 46 inactive TED patients. Comparative analyses of peripheral lymphocyte subsets were conducted between active and inactive patients. Subgroup analyses were performed based on sex, age, disease duration, and severity. Correlation analyses explored the associations between lymphocyte subsets and TED activity indicators. Prediction models for TED activity were established using objective indicators. Significantly elevated levels of CD3+CD4+ T cells were observed in active TED patients compared to inactive patients (P = 0.010). Subgroup analyses further revealed that this disparity was most prominent in females (P = 0.036), patients aged 50years and younger (P = 0.003), those with long-term disease duration (P = 0.022), and individuals with moderate-to-severe disease (P = 0.021), with age exerting the most substantial impact. Subsequent correlation analysis confirmed the positive association between CD3+CD4+ T cells and the magnetic resonance imaging indicator of TED activity among patients aged 50years and younger (P = 0.038). The combined prediction models for TED activity, established using objective indicators including CD3+CD4+ T cells, yielded areas under curve of 0.786 for all patients and 0.816 for patients aged 50years and younger. Peripheral CD3+CD4+ T cells are associated with disease activity of TED, especially in patients aged 50years and younger. Our study has deepened the understanding of the peripheral T cell profiles in TED patients.

Establishment and assessment of mortality risk prediction model in patients with sepsis based on early-stage peripheral lymphocyte subsets.

This study is aimed to explore the value of lymphocyte subsets in evaluating the severity and prognosis of sepsis. The counts of lymphocytes, CD3+ T cells, CD4+ T cells, CD8+ T cells, CD19+ B cells, and NK cells significantly decreased between day 1 and day 3 in both the survivor and the non-survivor groups. The peripheral lymphocyte subsets (PLS) at day 1 were not significantly different between the survivor and the non-survivor groups. However, at day 3, the counts of lymphocytes, CD3+ T cells, CD4+ T cells, and NK cells were remarkably lower in the non-survivor group. No significant differences in CD8+ T cells, or CD19+ B cells were observed. The PLS index was independently and significantly associated with the 28-day mortality risk in septic patients (OR: 3.08, 95% CI: 1.18-9.67). Based on these clinical parameters and the PLS index, we developed a nomograph for evaluating the individual mortality risk in sepsis. The area under the curve of prediction with the PLS index was significantly higher than that from the model with only clinical parameters (0.912 vs. 0.817). Our study suggests that the decline of PLS occurred in the early stage of sepsis. The new novel PLS index can be an independent predictor of 28-day mortality in septic patients. The prediction model based on clinical parameters and the PLS index has relatively high predicting ability.

Alterations of Peripheral Lymphocyte Subsets in Isolated Rapid Eye Movement Sleep Behavior Disorder.

Adaptive immune dysfunction may play a crucial role in Parkinson's disease (PD) development. Isolated rapid eye movement sleep behavior disorder (iRBD) represents the prodromal stage of synucleinopathies, including PD. Elucidating the peripheral adaptive immune system is crucial in iRBD, but current knowledge remains limited. This study aimed to characterize peripheral lymphocyte profiles in iRBD patients compared with healthy control subjects (HCs). This cross-sectional study recruited polysomnography-confirmed iRBD patients and age- and sex-matched HCs. Venous blood was collected from each participant. Flow cytometry was used to evaluate surface markers and intracellular cytokine production in peripheral blood mononuclear cells. Forty-four iRBD patients and 36 HCs were included. Compared with HCs, patients with iRBD exhibited significant decreases in absolute counts of total lymphocytes and CD3+ T cells. In terms of T cell subsets, iRBD patients showed higher frequencies and counts of proinflammatory T helper 1 cells and INF-γ+ CD8+ T cells, along with lower frequencies and counts of anti-inflammatory T helper 2 cells. A significant increase in the frequency of central memory T cells in CD8+ T cells was also observed in iRBD. Regarding B cells, iRBD patients demonstrated reduced frequencies and counts of double-negative memory B cells compared with control subjects. This study demonstrated alterations in the peripheral adaptive immune system in iRBD, specifically in CD4+ and INF-γ+ CD8+ T cell subsets. An overall shift toward a proinflammatory state of adaptive immunity was already evident in iRBD. These observations might provide insights into the optimal timing for initiating immune interventions in PD. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Dysbiosis of the Gut Microbiota in Patients with Psoriatic Arthritis is Closely Related to Lymphocyte Subsets and Cytokines.

The purpose of this research was to characterize the microbiota of patients with psoriatic arthritis (PsA) and to compare the relationship between the microbiota and peripheral lymphocyte subsets and cytokines. We collected stool samples from 13 PsA patients and 26 sex- and age-matched healthy controls (HCs) and researched the gut microbiota by sequencing the V3-V4 variable region of the bacterial 16S rRNA gene with the Illumina Miseq PE300 system. Flow cytometry was used to assess the peripheral lymphocyte subsets in these participants. Record measures of disease activity such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Alpha and beta diversity were assessed using results from QIIME2. Panel demonstrated the average relative abundance of the different genera in PsA and HCs. Correlation between clinical parameters and the relative abundance of the genus in samples was assessed by the Pearson correlation analysis using R (version 4.0.1). Compared with HC, the abundance of gut microbiota (Chao 1 and ACE) decreased in patients with PsA, and the diversity of bacteria (Shannon and Simpson indices) also decreased in PsA (Fig.1a). β Diversity analysis indicated differences in microbial communities between PsA and HC (Fig.1b, r = 0.039, p = 0.264, ANOSIM). Furthermore, 18 bacterial groups were significantly different at the genus level in PsA compared to HCs (p < 0.05) (Fig.2).In the phylum and genus, lymphocyte subsets and cytokines are associated with the microbiota. The gut microbiota of patients with PsA differs from HC, which was closely related to lymphocyte subsets.

Peripheral blood lymphocyte subsets predict the efficacy of TACE with or without PD-1 inhibitors in patients with hepatocellular carcinoma: a prospective clinical study.

Although peripheral blood lymphocyte subsets, particularly PD-1+ T cells, are promising prognostic indicators for patients with cancer. However, their clinical significance remains unclear. We prospectively enrolled 157 patients with hepatocellular carcinoma (HCC) treated with transcatheter arterial chemoembolization combined with or without PD-1 inhibitors. Twenty peripheral lymphocyte subsets and cytokines were analyzed. We analyzed the differences in PD-1+ T cells between patients treated with and without PD-1 inhibitors and their associations with tumor response, survival prognosis, and clinical features. We found that the baseline CD8+PD-1+ and CD4+PD-1+ T-cell frequencies in patients who had received PD-1 inhibitors were lower than those in patients who had not received PD-1 inhibitors (p < 0.001). In the former patients, there were no differences in PD-1+ T-cell frequencies between the responder and non-responder subgroups (p > 0.05), whereas in the latter patients, the levels of CD8+PD-1+ T cells, CD4+PD-1+ T cells, and CD8+PD-1+/CD4+PD-1+ ratio did not predict tumor response, progression-free survival (PFS), or overall survival (OS) (p>0.05). Furthermore, in multivariate analysis of patients treated with or without PD-1 inhibitors revealed that the levels of CD8+CD38+ T cells (OR = 2.806, p = 0.006) were associated with tumor response, whereas those of CD8+CD28+ T cells (p = 0.038, p = 0.001) and natural killer (NK) cells (p = 0.001, p = 0.027) were associated with PFS and OS. Although, these independent prognostic factors were associated with progressive tumor characteristics (p<0.05), with the exception of CD8+CD28+ T cells, changes in these factors before and after treatment were unassociated with tumor response (p > 0.05). Circulating CD8+CD38+ T cells, CD8+CD28+ T cells, and NK cells were identified as potential prognostic factors for tumor response and survival in patients with HCC. Contrastingly, although PD-1 inhibitors can effectively block the T cell PD-1 receptor, the baseline PD-1+ T-cell frequencies and changes in the frequency of these cells have limited prognostic value.

Peripheral Blood Lymphocyte Subsets in Factor VIII Inhibitor-Positive Patients with Severe Hemophilia A: A Case-Control Study.

The present study aimed to investigate different peripheral lymphocyte subsets in patients with severe hemophilia A (HA) and factor VIII (FVIII) inhibitor production. For this, age-matched cases of 19 FVIII inhibitor-positive (IP), 21 FVIII inhibitor-negative (IN) and 45 healthy controls were selected for study. Flow cytometry was used to analyze the peripheral lymphocyte subsets, including T, B, natural killer (NK) and NKT cells. The T cell subsets included CD3 + CD4-CD8- [double negative T (DNT)], CD3 + CD4 + CD8+ [double-positive T (DPT)], CD3 + CD4 + CD8- and CD3 + CD4-CD8+ T cells. Pairwise comparisons of absolute lymphocyte subset values were conducted among the three groups. The cut-off value for absolute lymphocyte counts was determined using receiver operating characteristic curve analysis. The results demonstrated that the absolute values of DPT cells in the IN and IP groups were significantly lower than those in the healthy control group (P = 0.007). The DNT values were also lower in severe HA patients with or without inhibitor than those in healthy subjects, but these differences were not statistically significant (P = 0.053). In addition, the absolute value of CD4+ Th cells in the IP group was lower than that in the healthy controls (P = 0.013). Although not statistically significant (P = 0.064), the absolute values of NKT cells were higher in the IN group compared with the IP group, and higher in the IP group compared with the healthy control group. There were no statistically significant differences in total T, B, CD8 + and NK cells among the IN, IP and healthy control groups. The cut-off value for absolute CD4+ Th cells in the IN group was < 598/µl. The decrease in absolute values of CD4+ Th cells in severe HA patients may contribute to the establishment of infused FVIII immune tolerance. If the CD4+ Th value remains > 598/µl, clinicians should be vigilant for possible FVIII inhibitor production, especially on days prior to FVIII exposure.

Predictive value of peripheral blood lymphocyte subsets for children with intravenous immunoglobulin-resistant Kawasaki disease

Based on peripheral blood lymphocyte subsets and common laboratory test indexes, this study aimed to construct a predictive scoring system for intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD). Children hospitalized in Tianjin Children's Hospital from January 2021 to March 2023 were included in the study (185 cases of IVIG-sensitive KD and 41 cases of IVIG -resistant KD). Forty-six healthy children matched for age and gender were selected as controls. The relative percentage and absolute counts of peripheral lymphocyte subsets were measured by flow cytometry. Multivariate logistic regression was used to identify the predictive factors for IVIG-resistant KD and to construct a predictive scoring system for predicting IVIG-resistant KD. The multivariate logistic regression analysis showed that CD4+ T cell absolute count, natural killer cell absolute count, serum sodium level, globulin level, and total bilirubin level were identified as predictive factors for IVIG-resistant KD (P<0.05). The predictive scoring system based on these factors achieved a sensitivity of 70.7% and a specificity of 83.8% in predicting IVIG-resistant KD. Peripheral blood lymphocyte subsets can serve as predictive indicators for IVIG-resistant KD in children. The introduction of this indicator and the establishment of a scoring system based on it can provide a higher accuracy in predicting IVIG-resistant KD in children.

Clinical Study of Lymphocyte Subsets in Patients with BCR/ABL Negative Myeloproliferative Neoplasms

Background Myeloproliferative neoplasms (MPNs) are stem cell-derived clonal myeloid malignancies characterized by abnormal proliferation of one or more lineages of myeloid cells in the bone marrow resulting in varying degrees of increase in peripheral blood cells.BCR-ABL-negative MPN mainly include essential thrombocythemia (ET), polycythemia vera (PV) and myelofibrosis (MF). It is still unclear that the pathogenesis of MPN,but a large number of studies have shown that MPN has abnormalities in the immune microenvironment. Aiming to investigate the potential contribution of lymphocyte subsets to the pathogenesis of MPN, we investigated the peripheral blood lymphocyte subsets in MPN patients with different clinical characteristics. Methods A total of 123 patients (57 ET, 17 PV and 49 PMF) with MPN admitted to the First Affiliated Hospital of Nanchang University from October 2020 to February 2023 were retrospectively studied. Dynamic data of lymphocyte subsets were collected. The levels of peripheral lymphocyte subsets were measured by flow cytometry before treatment, and their association with clinical characteristics was analyzed. Results: Among 123 patients with MPN，57 patients were diagnosed with ET with a median age of 62 years (range, 20-86), 17 patients were diagnosed with PV with a median age of 53 years (range, 19-70), 49 patients were diagnosed with PMF with a median age of 63 years (range, 26-81). 55 patients had varying degrees of splenomegaly, of which 14 (24.6%) patients with ET, 32 (65.3%) patients with PMF, and 9 (52.9%) patients with PV. Further comparing the incidence of splenomegaly in patients with ET, PV and PMF, it was found that the incidence of splenomegaly with PMF and PV was significantly higher than ET patients. There were significant differences in lymphocyte subsets counts in MPN patients compared to controls. We found that CD3+ T-cell counts, CD3+CD8+ T-cell counts, CD16+CD56+ NK-cell counts, CD19+CD3-B-cell counts, and Treg counts were reduced in patients in the MPN group in comparison to controls.And patients with PMF have reduced CD3+ T-cell counts, CD4+ T-cell counts and Terg-cell counts compared to ET patients. In different driver mutations patients we find that with CALR mutation had significantly lower CD16+CD56+ NK cell counts compared to controls,JAK2V617F mutation had significantly lower CD3 +T cell counts, CD3 +CD4 +T cell counts, CD3 +CD8 +T cell counts, CD16 +CD56 +NK cell counts, CD19 +CD3 -B cell counts compared to controls,triple negative patients had significantly lower CD3 +T cell counts, CD8 +T cell counts, CD16 +CD56 + NK cell counts compared to controls. Different clinical presentations have different immune characteristics.Patients with ET who develop splenomegaly show decreased CD8+ T cell counts compared to non- splenomegaly patients. We did not obtain similar findings in splenomegaly patients with ET and PV.Overt-PMF patients had lower of CD3+ T cell counts, CD4+ T cell counts, CD8+ T cell counts, Treg cell counts compared to pre-PMF patients. Conclusion PMF patients having more impaired immune function than ET and PV patients. Immune function was impaired differently in MPN patients with different driver mutations, The immune function of JAK2V617F mutations and triple-negative patients is more severely impaired than CALR mutated patients. Patients with splenomegaly, and overt-PMF patients have more impaired immune function.This is also consistent with the prognostic differences between the different clinical characteristics of MPN.

Disturbance of Adaptive Immunity System Was Accompanied by a Decrease in Plasma Short-Chain Fatty Acid for Patients Hospitalized During SARS-CoV-2 Infection After COVID-19 Vaccination.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can lead to disorders of immune function and a decrease in the diversity of intestinal flora. We aimed to explore the changes of circulating immune cell subsets and the plasma level of intestinal short-chain fatty acids (SCFAs) in patients with Coronavirus disease 2019 (COVID-19), further understanding the pathogenesis of COVID-19. The study included 83 newly diagnosed COVID-19 patients and 39 non-COVID-19 controls. All have completed a full course of vaccination against SARS-CoV-2. The levels of peripheral lymphocyte subsets and plasma cytokines were detected by flow cytometry. Targeted metabolomics was used to explore the level of SCFAs in plasma. Compared with the non-COVID-19 group, COVID-19 patients showed a decrease in CD19+B cells, CD4+T cells, CD8+T cells, NK cells, CD4+CD8+T cells and CD4-CD8-T cells (all p<0.001) and concomitantly an increase in sIL-2R, IL-6 and IL-10 (all p<0.005). These alterations were more pronounced in those critical patients. In addition, COVID-19 patients had lower levels of propanoic acid (PA), butyric acid (BA), isobutyric acid (IBA) and isohexanoic acid (ICA) (all p<0.01). Among them, the level of ICA is positively correlated with the absolute number of immune cells. Our study suggests the immune cell subsets in COVID-19 patients who had completed vaccination were still severely disturbed and concomitantly lower SCFAs, especially in severe patients with poor prognosis. Lower levels of plasma SCFAs may contribute to lymphopenia in COVID-19. The potential relationship between plasma SCFAs and immune cell reduction provides a new direction for the treatment of COVID-19.