Abnormal Immune Profile in Individuals with Kabuki Syndrome.

OBJECTIVE: To analyze the lymphocyte subsets in individuals with Kabuki syndrome for better characterizing the immunological phenotype of this rare congenital disorder. METHODS: We characterized the immunological profile including B-, T- and natural killer-cell subsets in a series (N = 18) of individuals with Kabuki syndrome. RESULTS: All 18 individuals underwent genetic analysis: 15 had a variant in KMT2D and 3 a variant in KDM6A. Eleven of the 18 individuals (61%) had recurrent infections and 9 (50%) respiratory infections. Three (17%) had autoimmune diseases. On immunological analysis, 6 (33%) had CD4 T-cell lymphopenia, which was preferentially associated with the KMT2D truncating variant (5/9 individuals). Eight of 18 individuals (44%) had a humoral deficiency and eight (44%) had B lymphopenia. We found abnormal distributions of T-cell subsets, especially a frequent decrease in recent thymic emigrant CD4 + naive T-cell count in 13/16 individuals (81%). CONCLUSION: The immunological features of Kabuki syndrome showed variable immune disorders with CD4 + T-cell deficiency in one third of cases, which had not been previously reported. In particular, we found a reduction in recent thymic emigrant naïve CD4 + T-cell count in 13 of 16 individuals, representing a novel finding that had not previously been reported.

The efficacy of neoadjuvant immunotherapy and lymphocyte subset predictors in locally advanced esophageal squamous cell carcinoma: A retrospective study.

BACKGROUND: Despite the recognized therapeutic potential of programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors in advanced esophageal squamous cell carcinoma (ESCC), their role in neoadjuvant therapy and reliable efficacy biomarkers remain elusive. MATERIALS AND METHODS: We retrospectively analyzed locally advanced ESCC patients who underwent surgery following a 2-cycle platinum and paclitaxel-based treatment, with or without PD-1 inhibitors (January 2020-March 2023). We assessed peripheral blood indexes and tertiary lymphoid structures (TLS) density to evaluate their impact on pathological response and prognosis, leading to a clinical prediction model for treatment efficacy and survival. RESULTS: Of the 157 patients recruited, 106 received immunochemotherapy (ICT) and 51 received chemotherapy (CT) alone. The ICT group demonstrated a superior pathological response rate (PRR) (47.2% vs. 29.4%, p = 0.034) with comparable adverse events and postoperative complications. The ICT group also showed a median disease-free survival (DFS) of 39.8 months, unattained by the CT group. The 1-year DFS and overall survival (OS) rates were 73% and 91% for the ICT group, and 68% and 81% for the CT group, respectively. We found higher baseline activated T cells, lower baseline Treg cells, and a decreased posttreatment total lymphocyte and CD4+/CD8+ ratio predicted an enhanced PRR. Reduced posttreatment CD4+/CD8+ ratio and increased NK cells were associated with prolonged survival, while higher TLS density indicated poorer prognosis. Among ICT group, a lower posttreatment CD4+/CD8+ ratio indicated longer DFS and reduced posttreatment B cells indicated longer OS. A nomogram integrating these predictors was developed to forecast treatment efficacy and survival. CONCLUSION: The combination of PD-1 inhibitors and chemotherapy appears promising for locally advanced ESCC. Evaluating the differentiation status and dynamic changes of peripheral blood immune cells may provide valuable predictive insights into treatment efficacy and prognosis.

Lymphocyte subsets for predicting inflammatory bowel disease progression and treatment response: a systematic review.

Background: Lymphocytes play a key role in the pathogenesis of inflammatory bowel disease (IBD) and are widely explored as promising prognostic indicators. We aimed to outline the existing evidences on the capability of lymphocyte subpopulations to predict disease progression and treatment response in patients with IBD. Methods: The protocol for this review was registered in PROSPERO (registration ID: CRD 42022364126). Systematic retrieval was conducted using PubMed, Embase, and Web of Science databases. Original articles on the prognostic value of lymphocyte subsets in IBD published up to April 8, 2023 were eligible for inclusion. The Newcastle-Ottawa Scale was used to evaluate the risk of bias. Results: Twenty studies were ultimately included: eight evaluated the prediction of disease progression and 12 focused on the prediction of treatment response. According to the Newcastle-Ottawa Scale, three studies were of high quality, 16 were of moderate quality, and only one was of low quality. T-cell subpopulations, including CD4+ T cells, CD8+ T cells, and γδ T cells, are revealed to have prognostic capacity. Transmembrane tumor necrosis factor α-bearing lymphocytes, CD4+ T cells, CD8+ T cells, and Plasma cells are found to have the potential to predict the response to anti-TNFα agents. In contrast memory T cells, CD4+ T cells, and naïve B cells may predict the response to vedolizumab. Conclusions: This systematic review identified several potential lymphocyte subset-related predictors. If verified in large cohort prospective studies, these findings could aid clinical decision-making. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022364126.

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

AIMS: To investigate the relationship between peripheral blood lymphocyte subsets and prognosis in patients with acute ischemic stroke (AIS). METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Clinical analysis of immune reconstitution after chemotherapy in children with acute lymphoblastic leukemia.

OBJECTIVES: The aim of this retrospective study was to investigate the influence of chemotherapy on the immune status of individual patients diagnosed with acute lymphoblastic leukemia (ALL) and to elucidate the clinical characteristics of immune reconstitution in ALL patients following chemotherapy. METHODS: Clinical data of children with ALL were gathered, including information on the number of lymphocyte subsets prior to chemotherapy, at the end of therapy, six months, and one year after the end of the treatment. RESULTS: A total of 146 children with ALL were included, and T cells, B cells, and NK cells all decreased to various degrees prior to treatment. The abnormal CD3 + T cell numbers group experienced a considerably higher mortality (21.9% vs. 6.1%) and recurrence rate (31.3% vs. 11.4%) compared to the normal group (P < 0.05). T cells, B cells, and NK cells were all significantly compromised at the end of therapy compared to the beginning of chemotherapy, with B cells being more severely compromised (P < 0.001). At the end of treatment, levels of B cells, CD4 + T cells, CD4/CD8, IgG and IgM in low risk (LR) group were significantly higher than those in intermediate risk (IR) group (P < 0.01), and levels of NK cells in LR group were evidently lower than those in IR group (P < 0.001). Six months after the end of therapy, all the above indicators recovered (P < 0.001) except CD4/CD8 ratio (P = 0.451). CONCLUSIONS: The immune systems of the ALL patients were severely compromised upon therapy withdrawal, particularly the B cells. At six months after the therapy ended, the B cells were basically restored to normal level, while the T-cell compartment was not. The impaired numbers of CD3 + T cell may contribute to a weakened anti-tumor response, potentially leading to a poorer prognosis.

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OBJECTIVES: Rejection remains the most important factor limiting the survival of transplanted kidneys. Although a pathological biopsy of the transplanted kidney is the gold standard for diagnosing rejection, its limitations prevent it from being used as a routine monitoring method. Recently, peripheral blood lymphocyte subpopulation testing has become an important means of assessing the body's immune system, however, its application value and strategy in the field of kidney transplantation need further exploration. Additionally, the development and utilization of routine test parameters are also important methods for exploring diagnostic strategies and predictive models for kidney transplant diseases. This study aims to explore the correlation between peripheral blood lymphocyte subpopulations and T cell-mediated rejection (TCMR) and antibody-mediated rejection (ABMR), as well as their diagnostic value, in conjunction with routine blood tests. METHODS: A total of 154 kidney transplant recipients, who met the inclusion and exclusion criteria and were treated at the Second Xiangya Hospital of Central South University from January to December, 2021, were selected as the study subjects. They were assigned into a stable group, a TCMR group, and an ABMR group, based on the occurrence and type of rejection. The basic and clinical data of these recipients were retrospectively analyzed and compared among the 3 groups. The transplant kidney function, routine blood tests, and peripheral blood lymphocyte subpopulation data of the TCMR group and the ABMR group before rejection treatment were compared with those of the stable group. RESULTS: The stable, TCMR group, and ABMR group showed no statistically significant differences in immunosuppressive maintenance regimens or sources of transplanted kidneys (all P>0.05). However, the post-transplant duration was significantly longer in the ABMR group compared with the stable group (P<0.001) and the TCMR group (P<0.05). Regarding kidney function, serum creatinine levels in the ABMR group were higher than in the stable group and the TCMR group (both P<0.01), with the TCMR group also showing higher levels than the stable group (P<0.01). Both TCMR and ABMR groups had significantly higher blood urea nitrogen levels than the stable group (P<0.01), with no statistically significant difference between TCMR and ABMR groups (P>0.05). The estimated glomerular filtration rate (eGFR) was lower in both TCMR and ABMR groups compared with the stable group (both P<0.01). In routine blood tests, the ABMR group had lower hemoglobin, red blood cell count, and platelet count than the stable group (all P<0.05). The TCMR group had higher neutrophil percentage (P<0.05) and count (P<0.05) than the stable group, and the ABMR group had a higher neutrophil percentage than the stable group (P<0.05). The eosinophil percentage and count in the TCMR group were lower than in the stable and ABMR groups (all P<0.05). Both TCMR and ABMR groups had lower basophil percentage and count, as well as lower lymphocyte percentage and count, compared with the stable group (all P<0.05). There were no significant differences in monocyte percentage and count among the 3 groups (all P>0.05). In lymphocyte subpopulations, the TCMR and ABMR groups had lower counts of CD45+ cells and T cells compared with the stable group (all P<0.05). The TCMR group also had lower counts of CD4+ T cells, NK cells, and B cells than the stable group (all P<0.05). There were no significant differences in the T cell percentage, CD4+ T cell percentage, CD8+ T cell percentage and their counts, CD4+/CD8+ T cell ratio, NK cell percentage, and B cell percentage among the stable, TCMR, and ABMR groups (all P>0.05). CONCLUSIONS: The occurrence of rejection leads to impaired transplant kidney function, accompanied by characteristic changes in some parameters of routine blood tests and peripheral blood lymphocyte subpopulations in kidney transplant recipients. The different characteristics of changes in some parameters of routine blood tests and peripheral blood lymphocyte subpopulations during TCMR and ABMR may help predict and diagnose rejection and differentiate between TCMR and ABMR.

Predictive value of circulating lymphocyte subsets and inflammatory indexes for neoadjuvant chemoradiotherapy response in rectal mucinous adenocarcinoma patients: A machine learning approach.

INTRODUCTION: In this study, we aimed to evaluate the predictive value of circulating lymphocyte subsets and inflammatory indexes in response to neoadjuvant chemoradiotherapy (NCRT) in patients with rectal mucinous adenocarcinomas (MACs). METHODS: Rectal MAC patients who underwent NCRT and curative resection at Fujian Medical University Union Hospital's Department of Colorectal Surgery between 2016 and 2020 were included in the study. Patients were categorized into good and poor response groups based on their pathological response to NCRT. An independent risk factor-based nomogram model was constructed by utilizing multivariate logistic regression analysis. Additionally, the extreme gradient boosting (XGB) algorithm was applied to build a machine learning (ML)-based predictive model. Feature importance was quantified using the Shapley additive explanations method. RESULTS: Out of the 283 participants involved in this research, 190 (67.1%) experienced an unfavorable outcome. To identify the independent risk factors, logistic regression analysis was performed, considering variables such as tumor length, pretreatment clinical T stage, PNI, and Th/Tc ratio. Subsequently, a nomogram model was constructed, achieving a C-index of 0.756. The ML model exhibited higher prediction accuracy than the nomogram model, achieving an AUROC of 0.824 in the training set and 0.762 in the tuning set. The top five important parameters of the ML model were identified as the Th/Tc ratio, neutrophil to lymphocyte, Th lymphocytes, Gross type, and T lymphocytes. CONCLUSION: Radiochemotherapy sensitivity is markedly influenced by systemic inflammation and lymphocyte-mediated immune responses in rectal MAC patients. Our ML model integrating clinical characteristics, circulating lymphocyte subsets, and inflammatory indexes is a potential assessment tool that can provide a reference for individualized treatment for rectal MAC patients.

Clinical Characteristics of Peripheral Lymphocyte Subtypes in Chronic Active Epstein-Barr Virus Infection.

BACKGROUND: We aimed to analyze the clinical characteristics of peripheral Epstein-Barr virus (EBV)-infected lymphocyte subtypes in children with chronic active EBV infection (CAEBV). METHODS: The levels of peripheral EBV infection of CD4+ T cells, CD8+ T cells, and CD56+ natural killer (NK) cells were determined by flow cytometry and quantitative polymerase chain reaction (qPCR) in patients with CAEBV from July 2017 to July 2022. RESULTS: In total, 112 children with CAEBV were evaluated. Of these, CD4+ type, CD8+ type, and CD56+ type were defined in 44, 21, and 47 patients, respectively. Patients with CD8+ T-cell type had a significantly higher frequency of rash, while hepatomegaly was more common in patients with CD4+ T-cell type. Generally, patients with CD8+ T-cell type had the lowest overall survival rate (P = .017). Patients treated with chemotherapy and hematopoietic stem cell transplantation (HSCT) had a better prognosis (P = .001). In multivariate analysis, rash, hemophagocytic lymphohistiocytosis, CD8+ T-cell type, and no decrease of plasma EBV-DNA after treatment were independent indicators of poor prognosis (P = .002, .024, .022, and .012, respectively). CONCLUSIONS: In children with CAEBV, rash was more frequent in patients with CD8+ T-cell type, whereas patients with CD4+ T-cell type were more likely to develop hepatomegaly. Patients with CD8+ T-cell type had a poor prognosis despite receiving chemotherapy or further HSCT.

Comparisons of different general anesthetic techniques on immune function in patients undergoing flap reconstruction for oral cancer.

BACKGROUND: Anesthetic-induced immunosuppression is of particular interest in tumor surgery. This study aimed to investigate the influence of the 4 most common general anesthetic techniques on immune function in patients undergoing flap reconstruction for oral cancer. METHODS: 116 patients were randomly divided into 4 groups. Patients in group S were given sevoflurane-based anesthesia. Group P was administered propofol-based anesthesia. The SD group received sevoflurane combined with dexmedetomidine anesthesia. The propofol combined with dexmedetomidine anesthesia (PD) group received PD. Blood samples were obtained at 5 time points: baseline (T0), 1 hour after the start of the operation (T1), end of the operation (T2), 24 hours (T3), and 48 hours (T4) after the operation. Lymphocyte subsets (including CD3+, CD4+, CD8+, and B lymphocytes) and dendritic cells were analyzed by flow cytometry. Blood glucose, norepinephrine, and cortisol levels were measured using ELISA and a blood gas analyzer respectively. RESULTS: In total, 107 patients were included in the final analysis. Immunological indicators, except CD8+ counts, were all decreased in groups S, P, and SD at T1-4 compared with the baseline value, and the counts of CD3+, CD4+, and dendritic cells, as well as CD4+/CD8+ ratios, were significantly higher in the PD group than in the S, P, and SD at T1-3 (P < .05). There were no significant differences between groups P and SD at any observation time point. Intraoperative stress indices, including norepinephrine and cortisol levels, were significantly lower in the PD group than in the other 3 groups at T1-2 (P < .05). CONCLUSION: These findings suggest that PD as a probably optimal choice can alleviate immunosuppression in patients undergoing flap reconstruction for oral cancer.

Evaluation of immunophenotypic alterations of peripheral blood lymphocytes and their sub-sets in uncomplicated P. Falciparum infection.

BACKGROUND: Malaria is a life-threatening parasitic disease typically transmitted through the bite of an infected Anopheles mosquito. There is ample evidence showing the potential of malaria infection to affect the counts of lymphocyte subpopulations in the peripheral blood, but the extent of alteration might not be consistent in all geographical locations, due to several local factors. Although Ghana is among the malaria-endemic countries, there is currently no available data on the level of alterations that occur in the counts of lymphocyte subpopulations during P. falciparum malaria infection among adults. AIM: The study was to determine the immunophenotypic alterations in the level of peripheral blood lymphocytes and their subsets in adults with uncomplicated P. falciparum malaria infection and apparently healthy participants. METHODS: The study was a cross-sectional comparative study conducted in two municipalities of the Volta region of Ghana. Blood samples were collected from study participants and taken through serology (P. falciparum/Pan Rapid Diagnostic Kits), microscopy (Thick and thin blood films) and Haematological (Flow cytometric and Full blood count) analysis. RESULTS: A total of 414 participants, comprising 214 patients with malaria and 200 apparently healthy individuals (controls) were recruited into this study. Parasite density of the malaria patients ranged from 75/µL to 84,364/µL, with a mean of 3,520/µL. It was also observed that the total lymphocytes slightly decreased in the P. falciparum-infected individuals (Mean ± SD: 2.08 ± 4.93 × 109/L) compared to the control group (Mean ± SD: 2.47 ± 0.80 × 109/L). Again, there was a significant moderate positive correlation between parasite density and haematocrit levels (r = 0.321, p < 0.001). Apart from CD45 + T-cells, more people in the control group had normal values for the lymphocyte subsets measured compared to the malaria patients. CONCLUSIONS: From the results obtained, there was high parasite density among the malaria patients suggestive of high intensity of infection in the case group. The malaria patients again showed considerable haematological alterations in lymphocyte sub-sets and the parasite density appeared to be strongly associated with CD4 + T-cell reduction. Also, the parasite density significantly associated with decreasing haematocrit levels. This indicates that lymphocyte subset enumeration can be used to effectively support malaria diagnosis.

Influence of cryoablation versus operation on circulating lymphocyte subsets in patients with early-stage renal cell carcinoma.

Immune response is known to play an important role in local tumor control especially in renal cell carcinoma (RCC), which is considered highly immunogenic. For localized tumors, operative resection or local ablative procedures such as cryoablation are common therapeutical options. For thermal ablative procedures such as cryoablation, additional immunological anti-tumor effects have been described.The purpose of this prospective study was to determine changes in peripheral blood circulating lymphocytes and various of their subsets in RCC patients treated with cryoablation or surgery in a longitudinal approach using extensive flow cytometry. Additionally, lymphocytes of RCC patients were compared to a healthy control group.We included 25 patients with RCC. Eight underwent cryoablation and 17 underwent surgery. Univariate and multivariable analysis revealed significantly lower values of B cells, CD4 and CD8 T cells, and various of their subsets in the treatment groups versus the healthy control group. Comparing the two different therapeutical approaches, a significant decline of various lymphocyte subsets with a consecutive normalization after three months was seen for the surgery group, whereas cryoablation led to increased values of CD69 + CD4 + and CD69 + CD8 + cell counts as well as memory CD8 + cells after three months.Treatment-naïve RCC patients showed lower peripheral blood lymphocyte counts compared to healthy controls. The post-treatment course revealed different developments of lymphocytes in the surgery versus cryoablation group, and only cryoablation seems to induce a sustained immunological response after three months.

High-dimensional single-cell analysis of human natural killer cell heterogeneity.

Natural killer (NK) cells are innate lymphoid cells (ILCs) contributing to immune responses to microbes and tumors. Historically, their classification hinged on a limited array of surface protein markers. Here, we used single-cell RNA sequencing (scRNA-seq) and cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) to dissect the heterogeneity of NK cells. We identified three prominent NK cell subsets in healthy human blood: NK1, NK2 and NK3, further differentiated into six distinct subgroups. Our findings delineate the molecular characteristics, key transcription factors, biological functions, metabolic traits and cytokine responses of each subgroup. These data also suggest two separate ontogenetic origins for NK cells, leading to divergent transcriptional trajectories. Furthermore, we analyzed the distribution of NK cell subsets in the lung, tonsils and intraepithelial lymphocytes isolated from healthy individuals and in 22 tumor types. This standardized terminology aims at fostering clarity and consistency in future research, thereby improving cross-study comparisons.

Diversity of group 1 innate lymphoid cells in human tissues.

Group 1 innate lymphoid cells (ILC1s) are cytotoxic and interferon gamma-producing lymphocytes lacking antigen-specific receptors, which include ILC1s and natural killer (NK) cells. In mice, ILC1s differ from NK cells, as they develop independently of the NK-specifying transcription factor EOMES, while requiring the repressor ZFP683 (ZNF683 in humans) for tissue residency. Here we identify highly variable ILC1 subtypes across tissues through investigation of human ILC1 diversity by single-cell RNA sequencing and flow cytometry. The intestinal epithelium contained abundant mature EOMES- ILC1s expressing PRDM1 rather than ZNF683, alongside a few immature TCF7+PRDM1- ILC1s. Other tissues harbored NK cells expressing ZNF683 and EOMES transcripts; however, EOMES protein content was variable. These ZNF683+ NK cells are tissue-imprinted NK cells phenotypically resembling ILC1s. The tissue ILC1-NK spectrum also encompassed conventional NK cells and NK cells distinguished by PTGDS expression. These findings establish a foundation for evaluating phenotypic and functional changes within the NK-ILC1 spectrum in diseases.

Lower proportion of intra-thyroidal B lymphocytes CD20+ associated to methimazole and lack of influence of iodide on lymphocyte subpopulations in Graves' disease.

Graves' disease (GD), an autoimmune thyroid disease, is one of the main autoimmune diseases in the general population. It is known that the pathophysiology of this disease may be related to immunological mechanisms dysregulation. These mechanisms can be influenced by GD therapies, such as iodide or antithyroid drugs (ATD). OBJECTIVE: Verify relation between clinical, biochemical and treatment modalities used prior to surgery and histopathological characteristics observed in total thyroidectomy products from patients previously diagnosed with Graves' disease. Furthermore, these data were related to composition of lymphocytic infiltrate in terms of proportions of lymphocytes CD4+, CD8+, CD25+ and CD20+. We aim to contribute to the understanding of the evolution pattern of GD, whose pathophysiology is not yet completely understood. METHODS: Cross-sectional study assessing thyroidectomy products for the presence of lymphocytic infiltrate, as well as the proportion and intensity of CD4+, CD8+, CD25+ and CD20+ markers. We selected 50 patients who underwent total or partial thyroidectomy in a tertiary service between 1996 and 2013 due to GD with histopathological confirmation. The control group (non-autoimmune disease group) consisted of 12 patients with histopathological data compatible with normal perilesional thyroid parenchyma. The intensity of lymphocytic infiltrate and immunohistochemical expression of the markers CD4+ (helper T lymphocytes), CD8+ (cytotoxic T lymphocytes), CD25+ (regulatory T lymphocytes) and CD20+ (B lymphocytes) were retrospectively evaluated and relationship with ultrasound, laboratory and clinical data was assessed. RESULTS: No differences were found in intensity, presence of lymphoid follicles, and expression of CD4+/CD8+/CD25+ in patients with GD who did or did not use ATD or iodide. In the group that did not use ATD, a higher proportion of CD20+ expression was found. The GD group was associated with hyperplastic epithelium and the control group was associated with simple epithelium. There was no difference in ultrasound thyroid volume between the groups. In GD patients with mild lymphocytic infiltrate, higher free thyroxin (FT4) levels were observed than those in patients with no infiltrate or moderate infiltrate. CONCLUSION: We found a lower proportion of intrathyroidal CD20+ B lymphocytes in patients under use of methimazole. However, no difference was observed in intrathyroidal lymphocyte subpopulations related to the short-term use of iodide. The understanding of thyroid autoimmunity, as well as identifying points of pharmacological modulation, are very important for advancement and improvement in treatments for these diseases.

Circulating innate lymphoid cells (cILCs): Unconventional lymphocytes with hidden talents.

Innate lymphoid cells (ILCs) are a group of lymphocytes that are devoid of antigen-specific receptors and are mainly found in tissues. The subtypes ILC1, 2, and 3 mirror T-cell functionality in terms of cytokine production and expression of key transcription factors. Although the majority of ILCs are found in tissue (tILCs), they have also been described within the circulation (cILCs). As a result of their better accessibility and putative prognostic value, human cILCs are getting more and more attention in clinical research. However, cILCs are in many aspects functionally distinct from their tILC counterparts. In fact, from the 3 ILC subsets found within the circulation, only for cILC2s could a clear functional correspondence to their tissue counterparts be established. Indeed, cILC2s are emerging as a major driver of allergic reactions with a particular role in asthma. In contrast, recent studies revealed that cILC1s and cILC3s are predominantly in an immature state and constitute progenitors for natural killer cells and ILCs, respectively. We provide an overview about the phenotype and function of the different cILC subtypes compared to tILCs in health and disease, including transcriptomic signatures, frequency dynamics, and potential clinical value. Furthermore, we will highlight the dynamics of the NKp44+ ILC3 subset, which emerges as prognostic marker in peripheral blood for inflammatory bowel disease and leukemia.

Epidemiologic trends and changes in humoral immunity and lymphocyte subsets levels among hospitalized children with Mycoplasma pneumoniae infection during 2019-2023.

PURPOSE: To understand the changes in humoral immunity and lymphocyte subsets levels among hospitalized children with Mycoplasma pneumoniae (MP) infection from 2019 to 2023. METHODS: This study retrospectively analyzed inpatients aged 0-14 years who were diagnosed with MP infection or MP pneumonia in a tertiary hospital from January 2019 to December 2023. The children were divided into three groups: before the implementation of nonpharmaceutical interventions (NPIs), during the implementation of NPIs, and after the NPIs being lifted. RESULTS: A total of 4103 patients were enrolled in this study, of whom 2125 were diagnosed with MP infection and 1978 were diagnosed with MP pneumonia. The number of MP infection cases dramatically decreased early during the implementation of NPIs, and the previous epidemic trend resumed after the NPIs were lifted, with the number of cases during the period 2019-2023 peaked in November 2023. In children aged < 5 years, the levels of IgA and IgM and the percentages of total T cells and cytotoxic T cells in the "before the implementation of NPIs" group were greater than those in the other groups, and the percentage of total B cells was lower than that in the other groups. In children aged ≥ 5 years, the IgM level in the "before the implementation of NPIs" group was greater than that in the other groups. CONCLUSION: The number of MP-infected hospitalized children decreased significantly after NPI implementation and reached its highest peak during 2019-2023 in November 2023. After the NPIs were lifted, the level of humoral immunity was decreased and balance lymphocyte subsets were disrupted, especially in children aged < 5 years. We should pay close attention to and prevent MP infection in a timely manner after epidemics caused by large respiratory pathogens.

Clonal associations between lymphocyte subsets and functional states in rheumatoid arthritis synovium.

Rheumatoid arthritis (RA) is an autoimmune disease involving antigen-specific T and B cells. Here, we perform single-cell RNA and repertoire sequencing on paired synovial tissue and blood samples from 12 seropositive RA patients. We identify clonally expanded CD4 + T cells, including CCL5+ cells and T peripheral helper (Tph) cells, which show a prominent transcriptomic signature of recent activation and effector function. CD8 + T cells show higher oligoclonality than CD4 + T cells, with the largest synovial clones enriched in GZMK+ cells. CD8 + T cells with possibly virus-reactive TCRs are distributed across transcriptomic clusters. In the B cell compartment, NR4A1+ activated B cells, and plasma cells are enriched in the synovium and demonstrate substantial clonal expansion. We identify synovial plasma cells that share BCRs with synovial ABC, memory, and activated B cells. Receptor-ligand analysis predicted IFNG and TNFRSF members as mediators of synovial Tph-B cell interactions. Together, these results reveal clonal relationships between functionally distinct lymphocyte populations that infiltrate the synovium of patients with RA.

Analysis of Immune Cell Subsets in Peripheral Blood from Patients with Engineered Stone Silica-Induced Lung Inflammation.

Silicosis caused by engineered stone (ES-silicosis) is an emerging worldwide issue characterized by inflammation and fibrosis in the lungs. To our knowledge, only a few reports have investigated leukocyte/lymphocyte subsets in ES-silicosis patients. The present study was designed to explore the proportions of the main lymphocyte subsets in ES-silicosis patients stratified into two groups, one with simple silicosis (SS) and the other with a more advanced state of the disease, defined as progressive massive fibrosis (PMF). The proportions of B (memory and plasmablasts) cells, T (helper, cytotoxic, regulatory) cells, and natural killer (NK) (regulatory and cytotoxic) cells were investigated by multiparameter flow cytometry in 91 ES-silicosis patients (53 SS patients and 38 PMF patients) and 22 healthy controls (HC). Although the total number of leukocytes did not differ between the groups studied, lymphopenia was observed in patients compared to healthy controls. Compared with those in healthy controls, the proportions of memory B cells, naïve helper T cells, and the CD4+/CD8+ T cells' ratio in the peripheral blood of patients with silicosis were significantly decreased, while the percentages of plasma cells, memory helper T cells, and regulatory T cells were significantly increased. For the NK cell subsets, no significant differences were found between the groups studied. These results revealed altered cellular immune processes in the peripheral blood of patients with ES-silicosis and provided further insight into silicosis pathogenesis.

Cytokines and lymphocyte subsets are associated with disease severity of severe fever with thrombocytopenia syndrome.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by severe fever with thrombocytopenia syndrome virus (SFTSV). Previous studies have indicated that SFTS patients have a high mortality rate, which may be related to cytokine storm and immune dysfunction. In our study, we analyzed differences in cytokines and lymphocyte subsets between severe and non-severe SFTS patients, with the aim of identifying predictors of severity. METHODS: We retrospectively analyzed demographic characteristics, clinical data, cytokine profiles, and lymphocyte subsets from 96 laboratory confirmed SFTS patients between April 2021 and August 2023. RESULTS: A total of 96 SFTS patients were enrolled, with a mean age of 65.05 (± 7.92) years old. According to our grouping criteria, 35 (36.5%) of these patients were classified as severe group, while 61 (63.5%) were classified as non-severe group. Univariate analysis revealed that age, interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), interferon-α (IFN-α), CD4 + T cell, and CD8 + T cell counts were risk predictors for the severity of SFTS. Further multivariable logistic regression analysis confirmed age, IL-6 levels, and CD4 + T cell counts as independent predictors of SFTS severity. CONCLUSIONS: Severe SFTS patients may experience cytokine storms and immune dysfunction. Aging, elevated levels of IL-6, and decreased CD4 + T cell count may serve as independent predictors for the severity of SFTS.

Predictive value of lymphocyte subsets and lymphocyte-to-monocyte ratio in assessing the efficacy of neoadjuvant therapy in breast cancer.

Lymphocyte subsets are the most intuitive expression of the body's immune ability, and the lymphocyte-to-monocyte ratio (LMR) also clearly reflect the degree of chronic inflammation activity. The purpose of this study is to investigate their predictive value of lymphocyte subsets and LMR to neoadjuvant therapy (NAT) efficacy in breast cancer patients. In this study, lymphocyte subsets and LMR were compared between breast cancer patients (n = 70) and benign breast tumor female populations (n = 48). Breast cancer patients were treated with NAT, and the chemotherapy response of the breast was evaluated using established criteria. The differences in lymphocyte subsets and LMR were also compared between pathological complete response (pCR) and non-pCR patients before and after NAT. Finally, data were analyzed using SPSS. The analytical results demonstrated that breast cancer patients showed significantly lower levels of CD3 + T cells, CD4 + T cells, CD4 + /CD8 + ratio, NK cells, and LMR compared to benign breast tumor women (P < 0.05). Among breast cancer patients, those who achieved pCR had higher levels of CD4 + T cells, NK cells, and LMR before NAT (P < 0.05). NAT increased CD4 + /CD8 + ratio and decreased CD8 + T cells in pCR patients (P < 0.05). Additionally, both pCR and non-pCR patients exhibited an increase in CD3 + T cells and CD4 + T cells after treatment, but the increase was significantly higher in pCR patients (P < 0.05). Conversely, both pCR and non-pCR patients experienced a decrease in LMR after treatment. However, this decrease was significantly lower in pCR patients (P < 0.05). These indicators demonstrated their predictive value for therapeutic efficacy. In conclusion, breast cancer patients experience tumor-related immunosuppression and high chronic inflammation response. But this phenomenon can be reversed to varying degrees by NAT. It has been found that lymphocyte subsets and LMR have good predictive value for pCR. Therefore, these markers can be utilized to identify individuals who are insensitive to NAT early on, enabling the adjustment of treatment plans and achieving precise breast cancer treatment.