Lymphocyte Subset Counts Research Articles

Dynamic changes in peripheral lymphocytes and antibody response following a third dose of SARS-CoV-2 mRNA-BNT162b2 vaccine in cancer patients

The aim of this study was to evaluate the association of circulating lymphocytes profiling with antibody response in cancer patients receiving the third dose of COVID-19 mRNA-BNT162b2 vaccine. Immunophenotyping of peripheral blood was used to determine absolute counts of lymphocyte subsets, alongside detection of IgG antibodies against receptor-binding-domain (RBD) of the SARS-CoV-2 Spike protein (S1) before booster dosing (timepoint-1) and four weeks afterward (timepoint-2). An IgG titer ≥ 50 AU/mL defined a positive seroconversion response. An IgG titer ≥ 4446 AU/mL was assumed as a correlate of 50% vaccine efficacy against symptomatic infections. A total of 258 patients on active treatment within the previous six months were enrolled between September 23 and October 7, 2021. The third dose resulted in an exponential increase in median anti-RBD-S1 IgG titer (P < 0.001), seroconversion rates (P < 0.001), and 50% vaccine efficacy rates (P < 0.001). According to ROC curve analysis, T helper and B cells were significantly associated with seroconversion responses at timepoint-1, whereas only B cells were relevant to 50% vaccine efficacy rates at timepoint-2. A positive linear correlation was shown between anti-RBD-S1 IgG titers and these lymphocyte subset counts. Multivariate analysis ruled out a potential role of T helper cells but confirmed a significant interaction between higher B cell levels and improved antibody response. These findings suggest that peripheral counts of B cells correlate with humoral response to the third dose of mRNA-BNT162b2 vaccine in actively treated cancer patients and could provide insights into a more comprehensive assessment of vaccination efficacy.

Peripheral Blood Lymphocyte Subsets as a Risk Predictor of Patients with Endometrioid Endometrial Cancer.

This study aimed to explore lymphocyte subsets for the personalized prediction of endometrioid endometrial cancer (EEC) risk and evaluated the correlation between immune cells and International Federation of Gynecology and Obstetrics (FIGO) staging in patients with EEC. A case-control study was conducted to analyze the clinical data of 421 patients admitted to Fujian Maternity and Child Health Hospital from October 2017 to December 2021. t-tests or Mann-Whitney U-tests were used to analyze the percentages and absolute counts of peripheral blood lymphocyte subsets in patients with EEC and patients without cancer. The independent risk factors for ECC and FIGO stage were analyzed via multivariate binary logistic regression. The receiver operating characteristic curve was calculated to evaluate the prediction efficacy of risk factors on ECC. The CD4+ T% in the 121 patients with EEC was lower than in the 300 patients without cancer (P = 0.013). The absolute counts of peripheral CD4+ T (P = 0.002) and T cells (P = 0.007) in 37 patients with EEC were lower than in 51 patients without cancer. Multivariate binary logistic regression analysis showed that CD4+ T% and natural killer cell (NK)% were independent risk factors for FIGO staging in patients with EEC. NK% was significantly higher in patients with advanced stage (FIGO III and IV) than those with early EEC (FIGO I and II) (P = 0.004). To determine the early and advance FIGO stage of EEC, the cutoff value of NK% was calculated as 19.94%. With the decrease of CD4+ T counts, the immune status of patients with EEC is impaired. NK cells may help in the evaluation of the prognosis of patients with EEC and are likely to be an independent risk factor for FIGO staging in patients with EEC.

Effect of Lymphocyte Subsets on Bone Density in Senile Osteoporosis: A Retrospective Study.

Several studies have shown that lymphocyte subsets can mediate the occurrence of osteoporosis (OP); however, the predictive ability of lymphocyte subsets in senile OP has not been elucidated. To investigate the ability of lymphocyte subsets to predict senile osteoporosis (OP). This study included 44 patients with senile OP and 44 without OP. Dual-energy X-ray absorptiometry (DEXA) was used to determine bone mineral density (BMD). Flow cytometry was used to analyze the absolute counts of the lymphocyte subsets and cytokine levels. Finally, the correlation between BMD and lymphocyte subset counts in the two groups was analyzed. There were no significant differences in age, sex, or weight between the OP and non-OP groups. The absolute counts of total T lymphocytes and CD8+ T lymphocytes in the OP group were significantly lower than those in the non-OP group. The levels of IFN-γ or TNF-α in the OP group were significantly higher or lower, respectively, than those in the non-OP group. PCA showed that age, BMI, total T lymphocytes, CD4+ T lymphocytes, CD8+ T lymphocytes, and B lymphocytes were the principal components of senile OP. The linear regression equation showed that BMD of the right femoral neck significantly decreased with a decline in CD8+ T lymphocyte counts. BMD decreased with a decrease in CD8+ T lymphocytes. The mechanism by which lower lymphocyte subsets lead to lower BMD may be related to abnormal bone metabolism caused by immune aging. Therefore, we considered that CD8+ T lymphocytes could be used to predict the incidence of senile OP.

The Recovery of the Absolute Lymphocyte Subpopulation Count in Cervical Cancer Patients after Radiotherapy

<h3>Purpose/Objective(s)</h3> Radiotherapy (RT) results in varying degrees of lymphopenia. However, to date, there is still no consensus on the persistence of lymphopenia after RT treatment for cervical cancer. Therefore, this study aimed to evaluate the dynamic changes of absolute lymphocyte subset count (ALSC) in cervical cancer patients after receiving RT. In addition, the study also explored the diagnostic value of the lymphocyte count (LC) in patients with declining ALSC <h3>Materials/Methods</h3> The peripheral blood ALSC was tested by flow cytometry before RT (baseline) and at regular follow-up intervals after completion of RT. The blood cell counts were also collected on the same day. Patient characteristics, tumor variables, and treatment factors were gathered for risk assessment. The primary endpoint was the degree of reduction in the lymphocyte subpopulation and the secondary endpoint was the predictive value of LC for declining ALSC. Logistic regression was used to identify the risk factors of lymphopenia, and the receiver operating characteristic (ROC) curve was used to assess the predictive value of LC. <h3>Results</h3> A total of 260 consecutive cervical cancer patients met the study criteria, among which 228 (87.7%) patients had a reduction in either one or some of the lymphocyte subpopulations. The median percentage decrease in ASLC ranged from 22.52% to 58.32%. When compared with the baseline the lymphocyte subpopulations dropped immediately after initiation of RT, to eventually reach their minimum levels at 3 to 6 months after completion of treatment. The B-lymphocyte and CD4+ to CD8+ ratios recovered within the first 6 months and the CD8+ T cell count recovered to normal levels within one year after completion of RT. In comparison, the CD3+ and CD4+ T cell counts persisted at low levels for one year and recovered five years after RT. The natural killer (NK) cells rarely decreased after RT. Multivariate logistic regression analysis identified advanced tumor stage and age above 60 years as independent risk factors affecting the count of lymphocyte cell subsets after RT. The ROC analysis confirmed that the LC obtained from a routine blood examination could be used to predict the count for each lymphocyte subtype except for the NK cell subtype. <h3>Conclusion</h3> The lymphocyte subpopulation counts decreased immediately after initiation of RT, to eventually reach their minimum levels after 3 to 6 months following completion of treatment, and it took several months or years to recover. Advanced tumor stage and age above 60 were identified as independent risk factors for lymphopenia in cervical cancer patients. The LC was a good predictor of ALSC decline. Therefore, this test could be used as a cheaper alternative to complex ALSC monitoring with flow cytometry.

Peripheral blood lymphocyte subsets are associated with the clinical outcomes of prostate cancer patients

BackgroundMany studies have sought associations between the total peripheral blood lymphocyte count and prostate cancer (PCa) prognosis, but not peripheral lymphocyte subsets. We explored the associations between the absolute counts of peripheral lymphocyte subsets and PCa patient survival. Methods135 PCa patients were included in this study. The log-rank test and Kaplan-Meier method were employed to compare overall survival (OS) and progression-free survival (PFS) rates. Univariate and multivariate Cox’s regression analyses were employed to identify prognostic factors. Flow cytometry analysis was used to determine the numbers of peripheral lymphocyte subsets. ResultsPCa patients with lower absolute counts of certain lymphocyte subsets showed poorer PFS and OS than those with higher absolute counts of these cells. The numbers of CD4+ T cells, CD3+ T cells, and natural killer (NK) cells were significantly higher in PCa patients of tumor node metastasis (TNM) Ⅰ-Ⅱ stages than those of TNM ⅠIII-IV stages. Univariate and multivariate Cox’s regression analyses of OS and PFS indicated that neutrophil numbers > 4.81*109/L, CD4+ T cells ≤ 254 /μL, and NK cells ≤ 136 /μL were unfavorably prognostic for patients with PCa. ConclusionsLower absolute counts of certain peripheral lymphocyte subsets (NK cells ≤ 136/μL and CD4+ T cells ≤ 254/μL) are prognostically unfavorable for PCa patients.

Dynamic analysis of immune status in patients with intracranial germ cell tumor and establishment of an immune risk prognostic model.

IntroductionImmune status was evaluated by means of lymphocyte subset counts and immune factors in cancer. This study analyzed the peripheral blood immune index and survival outcomes in intracranial germ cell tumor (iGCT) patients.MethodsPeripheral blood lymphocyte subset counts and levels of interleukin (IL)-2, IL-4, IL-6, IL-10, tumor necrosis factor (TNF), and interferon-γ (IFN) from 133 iGCT patients were collected and retrospectively analyzed. Their clinical information was extracted from the hospital database, and prognosis was confirmed by telephone visit. Patients (n=11) underwent prospective review and their samples of peripheral blood lymphocytes were verified.ResultsA total of 113 (84.2%) patients received comprehensive treatments, including 96 standard therapy (combination of full course chemotherapy and radiology with or without surgery) and 17 comprehensive but non-standard therapy (either without full course chemotherapy or with non-standard radiotherapy) and 98 (73.7%) reached complete or partial response. T lymphocytes (CD3+), cytotoxic T cells (CD3+CD8+ or Tc), and B lymphocytes (CD19+) decreased (p=0.047, p=0.004, and p<0.001, respectively), while activated cytotoxic T lymphocytes (CD8+CD25+) and IFN increased (p<0.001 and p=0.002, respectively) after treatment. Median survival was 45.33 months, and patients with increased Tc cells and activated Tc cells as well as IFN presented encouraging outcomes (p=0.039, p=0.041, and p=0.017 respectively). Regression analysis showed that non-increased Tc cells and non-increased activated Tc cells were independent factors of poor prognosis (p=0.016, HR=3.96, 95%CI=1.288-12.20; p=0.002, HR=4.37 95%CI= 1.738-10.97). Standard chemo-radiotherapy was independently related to reduced risk of death(p=0.022, HR=0.19, 95%CI=0.044-0.79). Consistence was seen in a nomogram established through retro and prospective studies. An immune risk model indicated the activated group (with both increased activated T cells and IFN levels) had the best prognosis, the mildly activated type with elevated IFN levels had intermediate outcome, and patients with the silent immune status had the worst outcomes (Log rank test, p=0.011).ConclusionImplementation of standard comprehensive treatments led to positive responses. Dynamic monitoring of peripheral blood lymphocyte subsets can be used as an auxiliary indicator for prognosis judgment.

BCG Vaccine-associated Complications in a Large Cohort of Children With Combined Immunodeficiencies Affecting Cellular and Humoral Immunity.

To present the details of Bacillus Calmette-Guérin (BCG)-vaccine associated complications (VACs) in combined immunodeficiencies (CID) patients. Five centers participated in this retrospective study and completed a data form, which included general patients' information, clinical and laboratory data. Among 236 CID patients, 127 were BCG vaccinated. 41.9% of patients with family history of CID and 17.1% who were diagnosed by screening were BCG vaccinated. Twenty-three patients (18.1%) developed BCG-VACs. The median age of VACs was 6 months and the median time from vaccination to complications was 6 months. The highest rate of BCG-VACs was recorded in patients receiving the Russian BCG strain compared to the Tokyo and Danish strains. Univariate analysis of T-lymphocyte subsets showed increased odds of BCG complications in patients with CD3+, CD4+, and CD8+ counts of ≤250 cells/µL. Only CD8 + count ≤250 cells/µL had increased such odds on multivariate analysis. VACs were disseminated in 13 and localized in 10 patients. Localized complication occurred earlier after vaccination (median: 4 months) compared with disseminated ones (median: 7 months). There were no significant associations between sex, administered vaccine strain, serum immunoglobulins levels, lymphocyte subsets counts, and the chance of having either localized or disseminated BCG-related complications. Although contraindicated, many patients with CID continue to be vaccinated with BCG. Low CD8 + count is a risk factor for BCG-related complications and localized complications occurred earlier than disseminated ones. Considerations should be undertaken by health care authorities especially in countries with high incidence of CID to implement newborn screening, delay the time of BCG vaccine administration beyond 6 months of age and to use the relatively safer strains like the Danish and Tokyo ones.

Identification of lymphocyte subgroups with flow cytometry in COVID-19 patients

Objective: We aimed to determine lymphocyte subgroups and activation status of flow cytometry in COVID-19 patients and examine their relationship with disease stage and length of hospital stay.&#x0D; Material and Method: Forty patients were analyzed in this study and compared with the age and sex-matched 40 healthy controls. COVID-19 patients have split as early and advanced-stage diseases. Flow cytometry assay was performed to determine the counts of lymphocyte subsets and activation status. Total lymphocyte count was calculated and CD45 (cluster of differentiation), CD3, CD4, CD8, CD19, CD27, CD38, CD56, CD57, and IgD were studied on lymphocyte gate. T helper / T cytotoxic rates and length of hospital stay were recorded.&#x0D; Results: The patients' CD3(+)CD4(+) ( T helper) count and CD27 expression on T cells counts were significantly lower, and CD57 expression on CD3(+)CD8(+) T cytotoxic cells were significantly higher (p

Sterile alpha motif and histidine-aspartic acid domain-containing protein 1 expression and its relationship with T cell activation in human immunodeficiency virus/acquired immune deficiency syndrome patients with lung-spleen deficiency syndrome pattern.

To investigate the relationship between antiviral restriction factor Sterile Alpha Motif and Histidine-Aspartic acid domain-containing protein 1 (SAMHD1) expression and T cell activation, furthermore, identifying objective indexes of lung-spleen deficiency symptom pattern. We assessed the profile of T lymphocyte subsets, characteristics of SAMHD1 and human leukocyte antigen DR (HLA-DR) expression in lung-spleen deficiency patients. At the same time, people living with human immunodeficiency virus / acquired immune deficiency syndrome (HIV/AIDS) (PLWHA) without obvious clinical symptoms and healthy donors in this area were used as controls. Immunohematologic indexes lower CD4 count, lower CD4/CD8 ratio and higher SAMHD1 level were found in lung-spleen deficiency patients. Furthermore, we demonstrated a positive relationship between SAMHD1 and HLA-DR level as well as with interferon factor in lung-spleen deficiency syndrome and patients without obvious clinical signs and symptoms groups. These data indicated the positive relationship between SAMHD1 and T cell activation which further elucidated the role of SAMHD1 in cellular immune response. Furthermore, combination of T lymphocyte subsets counts and SAMHD1 level may be used as clinical and biological reference basis for the differentiation and diagnosis of HIV / AIDS traditional Chinese medicine syndromes.

Construction of Machine Learning Models to Predict Changes in Immune Function Using Clinical Monitoring Indices in HIV/AIDS Patients After 9.9-Years of Antiretroviral Therapy in Yunnan, China

ObjectiveTo investigate trends in clinical monitoring indices in HIV/AIDS patients receiving antiretroviral therapy (ART) at baseline and after treatment in Yunnan Province, China and to provide the basis for guiding clinical treatment to obtain superior clinical outcomes.MethodsA total of 96 HIV/AIDS patients who had started and persisted in highly active ART treatment from September 2009 to September 2019 were selected. Of these, 54 had a CD4 cell count < 200 cells/μl while 42 had a CD4 cell count ≥ 200 cells/μl. Routine blood tests, liver and renal function, and lipid levels were measured before and 3, 6, 9, and 12 months after treatment. Lymphocyte subset counts and viral load were measured once per year, and recorded for analysis and evaluation. Three machine learning models (support vector machine [SVM], random forest [RF], and multi-layer perceptron [MLP]) were constructed that used the clinical indicators above as parameters. Baseline and follow-up results of routine blood and organ function tests were used to analyze and predict CD4+ T cell data after treatment during long-term follow-up. Predictions of the three models were preliminarily evaluated.ResultsThere were no statistical differences in gender, age, or HIV transmission route in either patient group. Married individuals were substantially more likely to have <200 CD4+ cells/μl. There was a strong positive correlation between ALT and AST (r = 0.587) and a positive correlation between CD4 cell count and platelet count (r = 0.347). Platelet count was negatively correlated with ALT (r = -0.229), AST (r = -0.251), and positively correlated with WBCs (r = 0.280). Compared with the CD4 cell count < 200 cells/μl group, all three machine learning models exhibited a better predictive capability than for patients with a CD4 cell count ≥ 200 cells/μl. Of all indicators, the three models best predicted the CD4/CD8 ratio, with results that were highly consistent. In patients with a CD4 cell count < 200 cells/μl, the SVM model had the best performance for predicting the CD4/CD8 ratio, while the CD4/CD8 ratio was best predicted by the RF model in patients with a CD4 cell count ≥ 200 cells/μl.ConclusionBy the incorporation of clinical indicators in SVM, RF, and MLP machine learning models, the immune function and recuperation of HIV/AIDS patients can be predicted and evaluated, thereby better guiding clinical treatment.

The relationship between absolute counts of lymphocyte subsets and clinical features in patients with pulmonary tuberculosis.

BackgroundThe aim of the present study is to investigate the clinical value and characteristics of peripheral blood lymphocyte subsets in patients with pulmonary tuberculosis (PTB) using flow cytometry.MethodsThe absolute counts of T, CD4+T, CD8+T, natural killer (NK), NKT and B lymphocytes in 217 cases of PTB were detected, and the variations in lymphocyte subset counts between different ages and genders and between aetiological detection results and chest radiography results were analysed.ResultsIn 75.3% of the patients with PTB, six subset counts were lower than the normal reference range, and 44% showed lower‐than‐normal CD4+T lymphocyte levels. The counts of T, CD4+T, CD8+T and B lymphocytes were significantly lower in patients aged >60 years, and the NKT cell counts were significantly lower in female patients than in male patients. Among the patients with positive aetiological results, 40.8% had reduced CD8+T counts; these were significantly lower than those in patients with negative aetiological results (P = 0.0295). The cell counts of T, CD4+T, CD8+T and B lymphocytes reduced as lesion lobe numbers increased. The counts of T, CD4+T and CD8+T lymphocytes were significantly higher in the group with lesions affecting one lobe than in the groups with two to three lobes or four to five lobes, and the counts of B lymphocytes were significantly higher in the group with one lobe and the group with two to three lobes than in the group with four to five lobes. The counts of CD4+T and CD8+T lymphocytes were highest in the no cavity group and showed a downward trend with the increase in cavities; the T lymphocyte count was significantly higher in the no cavity group than in the group with five or more cavities (P = 0.014), and the CD8+T lymphocyte count was significantly higher in the no cavity group than in the group with one to two cavities and the group with five or more cavities (P = 0.001 and 0.01, respectively).ConclusionsIn most patients with tuberculosis, immune function is impaired. The absolute counts of peripheral blood lymphocyte subsets are closely related to the aetiological results and lesion severity in patients with PTB; this could be used as evidence for immune intervention and monitoring curative effects.

Peripheral lymphocyte subset counts predict antibody response after SARS-CoV-2 mRNA-BNT162b2 vaccine in cancer patients: Results from the Vax-On-Profile study

BackgroundThe adaptive immune response following COVID-19 vaccination is essential for humoral immunogenicity and clinical protection against symptomatic infections. We present the results of circulating lymphocyte profiling and their correlation with antibody response in cancer patients tested serologically six months after receiving a two-dose schedule of mRNA-BNT162b2 vaccine. MethodsAbsolute counts of lymphocyte subsets were determined using peripheral blood immunophenotyping. We collected samples for flow cytometry analysis alongside quantitative detection of IgG antibodies against the receptor-binding domain (RBD) of the SARS-CoV-2 Spike protein (S1). An IgG titer ≥ 50 AU/mL defined a positive seroconversion response. Results311 patients were evaluable for lymphocyte profiling and serologic testing. A preliminary multivariate analysis revealed that cytotoxic chemotherapy was the most consistent factor associated with lower counts of all lymphocyte subpopulations. T helper and B cells were found to be useful in predicting the occurrence of a positive seroconversion response using ROC curve analysis. A significant positive linear correlation was shown when anti-RBD-S1 IgG titers were compared to these lymphocyte subset counts. Univariate analysis indicated that antibody titers and seroconversion rates were significantly improved in the high-level T and B cell subgroups. Multivariate analysis confirmed these significant interactions, as well as the negative predictive value of immunosuppressive corticosteroid therapy. ConclusionsThese findings suggest that simple and widely available peripheral counts of T helper and B cells correlate with humoral response to mRNA-BNT162b2 vaccine in actively treated cancer patients. Upon validation, our results could provide additional insights into the predictive assessment of vaccination efficacy.

Metagenomic Analyses Reveal Distinct Gut Microbiota Signature for Predicting the Neoadjuvant Chemotherapy Responsiveness in Breast Cancer Patients.

BackgroundGrowing evidence supports the modulatory role of human gut microbiome on neoadjuvant chemotherapy (NAC) efficacy. However, the relationships among the gut microbiome, tumor-infiltrating lymphocytes (TILs), and NAC response for breast cancer (BC) patients remain unclear. We thus proposed this preliminary study to investigate the relationship between gut microbiome and BC patients’ responses to NAC treatment as well as underlying mechanisms.MethodsPrior to receiving NAC, the fecal metagenome collected from 23 patients with invasive BC was analyzed. Patients were subsequently assigned to the NAC non-effectual group and the NAC effectual group based on their response to NAC. The peripheral T lymphocyte subset counts were examined by flow cytometry methods. CellMinor analysis was employed to explore the relationship between CD4 mRNA expression and the reaction of tumor cells to NAC drugs.ResultsThe gut microbiomes of the NAC non-effectual group showed characteristics of low diversity with low abundances, distinct metagenomic composition with decreased butyrate-producing and indolepropionic acid-producing bacteria, and increased potential pathobionts compared with the NAC effectual group. The combination of Coprococcus, Dorea, and uncultured Ruminococcus sp. serves as signature bacteria for distinguishing NAC non-effectual group patients from the NAC effectual group. The absolute numbers of CD4+ and CD8+ TIL infiltration in tumors in the NAC non-effectual group were significantly lower than those in the effectual group. Similar findings were reported for the CD4+ T lymphocytes in the peripheral blood (p’s < 0.05). NAC effectual-related signature bacteria were proportional to these patients’ CD4+ T lymphocyte counts in peripheral blood and tumors (p’s < 0.05). CellMinor analysis showed that the CD4 mRNA expression level dramatically climbed with increased sensitivity of tumor cells to NAC drugs such as cyclophosphamide, cisplatin, and carboplatin (p’s < 0.05).ConclusionsThe composition of the gut microbial community differs between BC patients for whom NAC is effective to those that are treatment resistant. The modulation of the gut microbiota on host CD4+ T lymphocytes may be one critical mechanism underlying chemosensitivity and NAC pathologic response. Taken together, gut microbiota may serve as a potential biomarker for NAC response, which sheds light on novel intervention targets in the treatment of NAC non-effectual BC patients.

Influence of Previous Disease-Modifying Drug Exposure on T-Lymphocyte Dynamic in Patients With Multiple Sclerosis Treated With Ocrelizumab

Background and ObjectivesTo investigate the longitudinal dynamic of lymphocyte subsets during treatment with ocrelizumab (OCR) in patients with multiple sclerosis (PwMS).MethodsA multicenter retrospective study was conducted in 161 PwMS starting treatment with OCR grouped in naive (naive, n = 40), switching from fingolimod (FTY, n = 52), and switching from other immunomodulating drugs (other, n = 69). Mean lymphocyte subset (total, CD3+, CD4+, CD8+, CD20+, and natural killer) counts were analyzed at baseline, 6 months, and 12 months. Rate of lymphocytopenia for each subset was calculated at all time points in all groups.ResultsMean total, CD3+, and CD4+ counts were significantly different among groups (p < 0.001) at all time points, whereas CD8+ and CD20+ counts only at baseline (p = 0.0157; p < 0.001), consistently lower in FTY. After adjustment for baseline values, interaction time*group was not statistically significant (p > 0.05 for each subset). The odds of lymphopenia were significantly higher among FTY patients compared with naive for total, CD3+, CD4+, and CD20+ cells at baseline, for total and CD4+ cells at the sixth month, and for total cells at the 12th month.DiscussionOCR per se exerts a modest depleting effect on T cells that seems rather due to a carryover phenomenon of previous therapies, particularly FTY. These data may help in the overall evaluation of the risk/benefit profile of treatment sequencing.

The Role of Lymphocyte Subset in Predicting Allograft Rejections in Kidney Transplant Recipients

Allograft rejection remains a significant challenge in managing post-transplant recipients despite the improvement in immunologic risk assessment and immunosuppressive therapy. Published literature including animal studies has demonstrated that the cells responsible for rejection are beyond the innate T and B cells, and other studies revealed evidence supporting natural killer (NK) cells' role in kidney allograft injury. This study aims to find the association between the peripheral blood lymphocyte subset counts, primarily NK cells, and the kidney allograft biopsy findings. This is a prospective cross-sectional study among a total of 100 kidney allograft biopsies in 61 kidney transplant recipients. The peripheral blood for the lymphocyte subset was sent just before the allograft biopsy. The patients' immunosuppression and other laboratory investigations were managed as per clinical practices by the attending nephrologist. Overall, the mean age of our patients was 43.72 ± 10.68 years old, and 55.7% of recipients were male. Higher counts of T cells (CD4+; 658.8 ± 441.4 cells/µL; P = .043) and NK cells (CD3-CD16+CD56+; 188 [interquartile range = 133.0-363.0 cells/µL]; P = .002) were associated with higher risk of allograft rejection in the initial analysis. Patients with an allograft age <12 months had significantly higher total T cells, CD4+ T cells, and NK cells in the rejection groups. However, after assessing factors associated with rejection in the multivariate analysis, we only found that being ABO-incompatible and having >497 CD4+ cells/µL had a higher odds of allograft rejection. Higher CD4± counts were associated with a higher risk of allograft rejection. However, there was no significant increase in CD8±, CD19±, and NK cells count in our cohort with allograft rejection.

Morbidity, Mortality, and Therapeutics in Combined Immunodeficiency: Data From the USIDNET Registry

Optimal management of patients with combined immunodeficiency, especially pertaining to hematopoietic stem cell transplantation (HSCT), remains unclear. To identify factors influencing HSCT and mortality in the population with combined immunodeficiency in North America. We identified 337 participants in the United States Immunodeficiency Network database with diverse forms of combined immunodeficiency and their characteristics, including demographic characteristics, laboratory values, infectious history, comorbidities, and treatment strategies. Univariate analysis was performed using logistic regression, whereas multivariate analysis was performed using multiple Cox proportional hazards. On univariate analysis, disseminated invasive viral infections and variants in STAT3, GATA2, and, DOCK8 were associated with increased odds of HSCT. Mucocutaneous fungal infections and variants in STAT3 were associated with increased odds of survival, whereas disseminated/invasive fungal infections, disseminated/invasive viral infections, and parasitic infections were associated with decreased odds of survival. On multiple variable Cox proportional hazards analysis, variants in ZAP70, nonspecific bacterial, and disseminated/invasive viral infections were associated with increased hazards of transplantation, whereas variants in multiple genes (RMRP, NEMO, DOCK8, CD40L, and CARD9), disseminated/invasive viral infections, autoimmune disease, and higher absolute lymphocyte count were associated with increased hazards of death. Importantly, demographic characteristics, basic lymphocyte subset counts, and absence of genetic diagnosis were not associated with HSCT or mortality. We determined that specific genetic diagnoses and infection burden impacts the decision to undergo HSCT in this cohort. In addition, certain genetic diagnoses and invasive viral infections carry an increased risk of mortality.

Comparison of the lymphocyte response to interval exercise versus continuous exercise in recreationally trained men

The purpose of this investigation was to compare changes in circulating lymphocyte subset cell counts between high-intensity interval exercise (HIIE), sprint interval exercise (SIE), and moderate-intensity continuous exercise (MICE). Recreationally active men (n ​= ​11; age: 23 ​± ​4 ​yr; height: 179.9 ​± ​4.5 ​cm; body mass: 79.8 ​± ​8.7 ​kg; body fat %:12.6 ​± ​3.8%; V̇O2max: 46.6 ​± ​3.9 ​ml⋅kg−1⋅min−1) completed a maximal graded exercise test to determine maximal oxygen uptake (V̇O2max) and three duration-matched cycling trials (HIIE, SIE, and MICE) in a randomized, counterbalanced fashion. HIIE consisted of fifteen 90-s bouts at 85% V̇O2max interspersed with 90-s active recovery periods. SIE consisted of fifteen 20-s bouts at 130% maximal power and 160-s active recovery periods. MICE was a continuous bout at 65% V̇O2max. Total exercise duration was 53 ​min in all three trials, including warm-up and cool-down. Blood was collected before, immediately post, 30 ​min, 2 ​h, 6 ​h, and 24 ​h post-exercise. Changes in lymphocyte subset counts, and surface expression of various markers were analyzed via flow cytometry. Changes were assessed using mixed model regression analysis with an autoregressive first order repeated measures correction. Significant decreases were observed in absolute counts of CD56dim NK cells, CD19+ B cells, CD4+ T cells, and CD8+ T cells 30 ​min and 24-h post-exercise in all three trials. Despite resulting in greater total work and oxygen consumption, MICE elicited similar changes in lymphocyte subset counts and receptor expression compared to both SIE and HIIE. Similarly, while the two interval trials resulted in differing oxygen consumption and total work, no differences in the lymphocyte response were observed. Though both forms of exercise resulted in declines in circulating lymphocyte cell counts, neither exercise type provides an immune-related advantage when matched for duration.

The Predictive Value of Changes in the Absolute Counts of Peripheral Lymphocyte Subsets for Progression and Prognosis in Breast Cancer Patients.

Background As the number and proportion of lymphocyte subsets are an important indicator of the immune function, an in depth understanding of the immune function of patients with malignant tumor has important clinical values for the treatment, prognosis, and evaluation of the disease. This retrospective study was to evaluate the clinical value of the absolute counts of lymphocyte subsets as potential blood biomarkers for progression and prognosis in breast cancer patients. Methods A total of 237 BC patients and 55 age-matched female normal healthy donors were included in this study. Flow cytometry was used to determine the absolute counts and the percentages of CD3+, CD4+, CD8+, B, and NK cells. The receiver operating characteristic curve (ROC) was used to evaluate the accuracy of absolute count of lymphocyte subsets in the curative efficacy assessment. The clinicopathological parameters influencing the disease progression were determined by Cox proportional hazards regression. Progression-free survival (PFS) was estimated using the Kaplan–Meier method with the log-rank test. Results: Compared with the healthy donors, the absolute counts of lymphocyte subsets in patients decreased significantly. ROC analysis showed that the area under the curve of the CD4+ absolute count was 90% (95% confidence interval 0.859–0.940), and the sensitivity and specificity were 80.9% and 85.3%, respectively. The analysis of Cox regression showed that the cutoff value of the CD4+ absolute count ≥451 cells/μL might be a favorable prognostic factor. Multivariate analysis of prognostic factors of PFS showed that the CD4+ and CD8+ absolute count were independent factors for predicting PFS. Conclusions The remarkably impaired absolute counts of the CD3+, CD4+, CD8+, B, and NK cells in patients with breast cancer can be used as potential susceptible biomarkers to evaluate the patient's immune status. The higher level of CD4+ and CD8+ absolute counts probably contributed to the longer PFS and favorable outcome of BC patients.

Immune Reconstitution in Pediatric Aplastic Anemia after Allogeneic Hematopoietic Stem-cell Transplantation.

Background: Previous studies had revealed that immune reconstitution (IR) after allogeneic hematopoietic stem-cell transplantation (allo-HSCT) affected the clinical prognosis of patients. However, few studies were based on pediatric patients and patients with aplastic anemia (AA). The purpose of this research was to analyze IR of pediatric AA after HSCT and further explore its clinical prognostic value.Methods: The whole of 61 pediatric patients with AA who underwent HSCT were enrolled. Lymphocyte subsets count in peripheral blood, CD4+/CD8+ T cell ratio, and serum concentration of immunoglobulins were detected using flow cytometry at regular intervals after HSCT.Results: Innate immunity recovered faster than adaptive immunity, T lymphocytes recovered faster than B lymphocytes. The number of transfused CD34+ cells and the implantation time of ANC significantly affected the early rapid IR of CD3+ T cells. The degree of HLA site coincidence significantly affected the early rapid IR of CD19+ B cells. The number of transfused MNC and CD34+ cells significantly affected the early rapid IR of CD56+ NK cells. The overall survival (OS) and failure-free survival (FFS) of CD56+ NK cells in early rapid IR group were higher than those in non-IR group. The CD3+ T cell early rapid IR group and CD8+ T cell early rapid IR group had higher OS than the non-IR group.Conclusion: Early rapid IR after HSCT is a good predictor of clinical prognosis in children with AA. This study provides a reasonable prediction for early rapid IR, which may improve clinical outcomes of children.

Efficacy and safety of Ma's Bamboo-based medicinal moxibustion therapy for chronic fatigue syndrome

Abstract Background: Chronic fatigue syndrome (CFS) is a recurrent functional disease with an unknown pathogenesis. Modern treatment mainly focuses on symptomatic and supportive care, but no specific treatment has emerged. Ma's Bamboo-based Medicinal Moxibustion therapy is a folk traditional Chinese medicine developed in Jinsha County, Guizhou Province. Over a long period of practice in the primary health care setting, it has been confirmed in folk medicine that the therapy can significantly improve the symptoms of patients with CFS, but there is no sufficient and scientific clinical evidence. Therefore, this randomised controlled pilot study was designed to preliminarily evaluate the efficacy and safety of Ma's Bamboo-based Medicinal Moxibustion therapy. Methods/design: This is a parallel, randomized, controlled, and exploratory study. Sixty patients with CFS admitted to the First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine will be randomly assigned to the experimental or control group. The experimental group will receive Ma's Bamboo-based Medicinal Moxibustion therapy, whereas the control group will undergo conventional acupuncture. Both groups will be treated once daily for 6 consecutive days as a course of treatment, and two courses separated by 1 day will be completed (12 total treatments). All patients will undergo follow-up after the end of treatment. The baseline period is 2 days. The Fatigue Assessment Instrument score as the primary efficacy measure and secondary efficacy measures, including the Clinical Symptom Score and Fatigue Scale-14, will be evaluated at baseline, after one and two courses of treatment, and during follow-up. Serum T lymphocyte subset counts (CD3 +, CD4 +, CD8 +, CD4 +/CD8 +) and safety measures ((blood routine test, liver and kidney function and electrocardiogram) will be evaluated at baseline and after two courses of treatment. All adverse events occurring between baseline and the end of follow-up will be summarised at the end of the follow-up. Discussion: The results of this trial will clarify whether Ma's Bamboo-based Medicinal Moxibustion therapy can improve the symptoms of patients with CFS and provide preliminary evidence for the effectiveness and safety of Ma's Bamboo-based Medicinal Moxibustion therapy for this indication. Ethics approval: This study has been approved by the Ethics Review Committee of the First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine (No.K2020–038). Trial Registration: Chinese Clinical Trial Registry, ChiCTR2000038860. Registered on 7 October 2020.