Lymphocyte Subsets In Patients Research Articles

Features of effector lymphocyte subsets in patients with uveal melanoma in recurrent and chronic herpesvirus infection

The aim of the study is to conduct a comparative analysis of percentages for peripheral blood effector lymphocyte subsets in patients with uveal melanoma manifested by recurrent and chronic herpesvirus infection. There were 141 subjects enrolled: 70 patients with uveal melanoma, 38 patients with corneal ulcers and involvement of the uveal tract as well as 33 healthy donors. Immunophenotyping was performed by using laser flow cytometry with panel of monoclonal antibodies to differentiate lymphocyte subpopulations. IgM and IgG antibodies to herpesvirus infections were determined by using enzyme-linked immunosorbent assay on an automatic ELISA analyzer Lazurit (USA) with diagnostic kits of CJSC “Vector-Best” (Koltsovo). The data obtained showed that the absolute number of blood lymphocytes (CD45+) in patients with uveal melanoma did not differ from those in healthy donors. In contrast, patients with corneal ulcers and involvement of the uveal tract had this parameter increased. A decreased relative and absolute count of T cells (CD3+) in uveal melanoma, but increased absolute CD3+ number in inflammation was observed. No difference in relative and absolute content of the CD3+CD4+ helper/inducer subpopulation in patients with recurrent herpesvirus infections was found. Corneal ulcers in cancer patients revealed significantly increased absolute level of CD3+CD4+ helpers/inductor cells. Chronic herpesvirus infection in uveal melanoma patients showed increased relative and absolute number of cytotoxic T lymphocytes (CD3+CD8+). Recurrent herpesvirus infection was featured with decreased relative number of T lymphocytes (CD3+CD8+), upon inflammation, there was noted increased absolute and decreased relative number compared with healthy subjects. Double positive T cells increased in tumor and inflammation. B lymphocytes (CD19+) increased in melanoma and inflammation. The relative number of blood natural killer cells (CD16+CD56+) in uveal melanoma increased upon recurrent infection. Inflammation was coupled to decreased relative level of natural killer cells (CD16+CD56+). Melanoma showed no changes in CD4+/ CD8+ ratio; upon inflammation, its increase was noted in acute and chronic herpesvirus infections (p 0.05). The suppression of the immune system in uveal melanoma, restricting antiviral defense, was revealed. The data obtained seem to be important for development of personalized approaches to prognosis and treatment of patients with uveal melanoma.

Effect of Pembrolizumab on T Lymphocyte Subsets in Patients with Advanced Non-small Cell Lung Cancer and Its Therapeutic Effect

背景与目的本研究旨在探究非小细胞肺癌患者应用帕博利珠单抗治疗前后外周血淋巴细胞亚群的变化及临床意义。方法选取2015年1月-2020年12月至青岛大学附属医院及潍坊市人民医院行帕博利珠单抗治疗的32例非小细胞肺癌的患者为观察组，另外选取同期30例健康查体者为对照组。治疗前、治疗后第1、2、4周期，采用流体细胞术检测患者外周血淋巴细胞亚群水平的变化。结果非小细胞肺癌患者治疗前的CD3+、CD4+、CD4+/CD8+指标较对照组明显下降（P < 0.05），CD8+水平明显升高（P < 0.05）；应用帕博利珠单抗治疗1个周期后，淋巴细胞亚群较免疫治疗前的变化未见明显统计学差异；治疗2周期后CD3+、CD4+、CD4+/CD8+数值较治疗前升高（P > 0.05），CD8+指标较治疗前下降（P < 0.05）；治疗4周期后CD3+、CD4+、CD4+/CD8+数值较治疗前得到显著改善（P < 0.05），CD8+指标较治疗前明显下降（P < 0.05）；疗效达到疾病稳定（stable disease, SD）/部分缓解（partial response, PR）患者在治疗过程中，第4周期的CD3+、CD4+、CD4+/CD8+数值较治疗前升高（P < 0.05），CD8+指标较治疗前降低（P < 0.05）；疗效达到疾病进展（progressive disease, PD）患者在治疗过程中，淋巴细胞亚群变化较治疗前均没有明显统计学差异（P > 0.05）。同时本文通过分析显示，程序性死亡受体配体1（programmed cell death ligand 1, PD-L1）表达与否及病理学类型对免疫治疗效果的影响不明显。通过多因素分析显示，同时观察CD3+、CD4+、CD8+的变化对预测免疫治疗效果更有意义。结论帕博利珠单抗可以调节非小细胞肺癌患者T淋巴细胞亚群的变化，改善患者机体的免疫状态，且未见明显不良反应，同时治疗过程中监测淋巴细胞亚群变化可预测免疫治疗效果。

Analysis of blocking antibodies and lymphocyte subsets in patients with recurrent reproductive failure

This study aimed to explore the relationship between recurrent reproductive failure (RRF) and blocking antibody (BA) and lymphocytes, to explore the difference of immune status between recurrent spontaneous abortion (RSA) and recurrent implantation failure (RIF) patients. We undertook a retrospective analysis of BA and lymphocyte subsets detected by flow cytometry in 720 RRF patients (411 RSA and 309 RIF patients) who were treated at Shanxi Maternal and Child Health Hospital from April 2015 to October 2019. The BA negative rate of RRF patients was 81.80%, which was significantly higher than that of normal women (23.46%) (p < 0.05). There was no significant difference in BA negative rates between RSA and RIF patients. Compared with the normal value, the percentage of CD3+ T lymphocytes and CD3+CD4+ T lymphocytes in RRF patients were 71.1% (65.9–76.0) and 36.8% (32.5–41.9) respectively, which were significantly lower than the normal value (p < 0.05). The percentage of B cells in RSA patients [11.0 (8.8–13.9)] was significantly lower than that in RIF patients [11.9 (9.4–14.8)]. The occurrence of RRF is related to the lack of BA and the change of lymphoid subsets. There are some differences in immune status between RSA and RIF patients.

Effect of chemoradiotherapy on the proportion of circulating lymphocyte subsets in patients with limited-stage small cell lung cancer.

Chemoradiotherapy (CRT) is the standard treatment for limited-stage small cell lung cancer (LS-SCLC), which can exert anti-tumor effects by regulating immune cells. Different immune cell subsets are associated with a specific sensitivity to CRT. The purpose of this study was to characterize the proportion or composition of peripherallymphocytes in patients with LS-SCLC before and after CRT, and evaluate their prognostic value. A total of 98 patients with LS-SCLC were enrolled. The expression of CD3, CD4, CD8, CD45RA, CD45RO, CD38, CD56, and CD19 on the surface of peripheral blood cells was detected by flow cytometry and retrospectively analyzed. The relationship between the proportion of lymphocyte subsets, progression-free survival (PFS), and overall survival (OS) was evaluated using a log-rank test and Cox regression model. The median PFS was 12.3months and the median OS was 21.7months. Compared with the pre-treatment specimens, post-treatment lymphocytes had increased proportions of CD3+, CD3+CD8+, CD8+CD38+ T cells, and NKT cells, and a decreased proportion of CD3+CD4+ T cells, CD4+CD45RA+ T cells, B cells, NK cells, and CD4/CD8 ratio. Univariate and multivariate analyses showed that prophylactic cranial irradiation, high percentages of CD4+CD45RA+, CD8+CD38+ T cells after CRT independently predicted superior PFS. Male patients with a high baseline CD4+CD45RO+ T cell ratio predicted a poor OS. CRT induced changes in the proportion of circulating lymphocyte subsets in LS-SCLC, which is helpful for designing a regimen of immune drugs to be combined with CRT. The prognostic value of the proportion of lymphocytes aids in understanding the role of peripheral immune profiles in LS-SCLC.

Changes of lymphocyte subsets in patients with COVID-19 and clinical significance: a case-control observational study

Abstract Objective: To investigate and analyze changes of T lymphocyte and other lymphocyte subsets in the peripheral blood of patients with coronavirus disease 2019 (COVID-19), with the goal of improving clinical understanding and the value of research applications. Methods: General data of 66 confirmed COVID-19 patients admitted to the Fifth Medical Center of Beijing PLA General Hospital from January 2 to March 23, 2020 were collected in this retrospective case-control observational study, and they were divided into mild (n = 26), mid-grade (n = 19), and severe/critical disease groups (n = 21) according to disease severity. Neutrophils, lymphocytes, neutrophil/lymphocyte ratios, CD4 absolute counts, CD8 absolute counts, and CD4/CD8 expression ratios of peripheral whole blood among the three patient groups were compared. The study protocol was approved by the Ethics Committee of the Fifth Medical Center, General Hospital of Chinese PLA (approval No. 2020-69-D) on May 5, 2020. Results: Among the 66 COVID-19 patients examined, 38 were male and 28 were female, with an average age of 53 ± 17 years. Among patients, 26 cases were mild, 19 cases were mid-grade, and 21 cases were severe/critical. Neutrophils, neutrophil/lymphocyte ratios, and CD4+/CD8+ ratios of the severe/critical group were significantly higher compared with mild and mid-grade groups (P &lt; 0.01); however, there was no obvious difference between mid-grade and mild groups (P &gt; 0.05). Lymphocytes, CD4 absolute counts, and CD8+ absolute counts of the severe/critical group were significantly lower compared with mild and mid-grade groups (P &lt; 0.01); however, there was no significant difference between mid-grade and mild groups (P &gt; 0.05). Conclusion: Counts of lymphocytes and T lymphocytes in severe/critically ill patients were decreased, which is of great significance for the identification of severe and critical COVID-19 patients.

Immunotherapy-induced pneumonitis in non-small cell lung cancer patients: current concern in treatment with immune-check-point inhibitors.

Purpose Immune-related adverse events (IrAEs) are auto-immune reactions associated with immune checkpoint inhibitor-based therapy (ICI). To date, little is known about immunotherapy-induced pneumonitis (IIP). In this study, we investigated the clinical and CT features of IIP in non-small cell lung cancer (NSCLC) patients treated with ICI. Methods CT images and clinical data of 98 NSCLC patients in our hospital were retrospectively analyzed after ICI therapy, and the incidence, onset time, CT findings, grade, treatment and prognosis of IIP were recorded. Results Nineteen patients developed IIP, which occurred 42∼210 days after ICI therapy, and the median time was 97 days. The CT findings for IIP showed multifocal ground-glass opacity (GGO) in 5 cases, patchy shadows in 6 cases, mixed distribution of patchy and strip-like shadows in 4 cases, and patchy shadows with honeycomb lung in 4 cases. The mean age and proportions of smokers, CD3+ and CD4+ of T lymphocyte subset in patients with IIP were significantly higher than those in patients without IIP (all p < 0.05). Among 19 patients with IIP, there were 10 patients with grade 1 ~ 2 and 9 patients with grade 3 ~ 4; 13 patients received hormone therapy, 12 of them were improved or stable, and 1 patient got worse after hormone therapy. No deaths from IIP were found. Conclusion IIP is a relatively rare but serious adverse event, and it is sensitive to hormone therapy. Its CT manifestations are diverse, and timely detection and treatment are the keys to reduce IIP.

Prognostic value of peripheral blood T lymphocyte subsets in clear cell renal cell carcinoma.

BackgroundTo date, few studies have evaluated the role of peripheral blood T lymphocyte subsets in patients with clear cell renal cell carcinoma (ccRCC). Here we measured the levels of peripheral blood T lymphocyte subsets and evaluated its prognostic value in ccRCC.MethodsData from 122 patients with RCC from January 2018 to January 2020 were collected. Preoperative peripheral blood T lymphocyte subsets and medical records were analyzed. Kaplan-Meier cures and log rank test were used for analyzing overall survival (OS). Univariate and multivariate survival analyses were underwent by performing the Cox proportional hazards models. Correlations were tested by Pearson’s correlation analysis.ResultsOf 122 patients, a total of 80 ccRCC patients was enrolled. Patients with low CD3+ T cells and low CD4+/CD8+ ratio displayed a worse OS than patients with high CD3+ T cells and high CD4+/CD8+ ratio (P=0.029 and 0.002, respectively). Multivariate analyses showed CD3+ T cells and CD4+/CD8+ ratio were independent predictive factors for the OS (HR: 0.295, 95% CI, 0.091–0.956; P=0.042 and HR: 0.244, 95% CI, 0.065–0.920; P=0.037, respectively). Moreover, NLR negatively correlated with both levels of CD3+ T cells and CD4+/CD8+ ratio (P<0.001, r=−0.398 and P=0.012, r=−0.280, respectively).ConclusionsThe findings of our study suggest that preoperative CD3+ T cells and CD4+/CD8+ ratio in peripheral blood are independent predictors for patients with ccRCC.

Changes of peripheral lymphocyte subset in patients with SARS-CoV-2 infection during the whole course of disease

ABSTRACT Background: Little is known about changes in lymphocyte subsets after SARS-CoV-2 infection. Methods: Clinical data of 580 COVID-19 patients hospitalized in Zhongnan Hospital of Wuhan University from 20 December 2019, to 8 March 2020, were retrospectively analyzed. The relation of lymphocyte subsets and severity or prognosis of disease were analyzed. Results: At 2–3 weeks after the onset of symptoms, lymphocyte subsets decreased to the lowest levels. The levels of lymphocyte subsets in asymptomatic patients were close to healthy persons, except for CD8+ T lymphocyte cells. The levels of lymphocyte subsets in patients with severe illness were lower than that in patients with mild-to-moderate illness (P < 0.01). Similarly, among patients with severe illness, lower levels of lymphocyte subsets were found in dead patients compared to survivors (P < 0.001). Moreover, by comparing the results of the same patients at different stages of the disease, we found levels of lymphocyte subsets were lower in the acute phase compared to that in convalescent-phase (P < 0.001). However, the levels of lymphocyte subsets in patients who had SARS-CoV-2 viral load >5000 copies/ml and 500–5000 copies/ml were at similar levels. Conclusions: Lymphocyte subsets are a good biomarker to assess the severity and prognosis of the disease at 2–3 weeks after the onset of symptoms.

CD8dimCD3+ lymphocytes in fever patients might be biomarkers of active EBV infection and exclusion indicator of T-LGLL.

Background: Massive monoclonal or oligoclonal expansion of CD8+ T cells is a notable feature of primary infections of the Epstein-Barr virus (EBV). However, the clinical significance of this expansion is not clear. Results: An increase in the CD8dimCD3+ lymphocyte subset in patients with active EBV infection was due to caspase-8-dependent apoptosis was found using flow cytometry in this study. The number of these cells was associated with the illness severity. Pan-T-cell antigen and receptor analyses were also compared in patients with active EBV infections and T-cell large granular lymphocytic leukemia to provide additional diagnostic information. Conclusion: The increase in CD8dimCD3+ cells could be a biomarker of active EBV infection and an exclusion indicator of T-cell large granular lymphocytic leukemia with flow cytometric analysis.

Dynamic changes of peripheral blood lymphocyte subsets in acute ischemic stroke and prognostic value.

ObjectiveTo explore dynamic changes of peripheral blood lymphocyte subsets in patients with acute ischemic stroke (AIS) and the relationship with stroke severity and long‐term outcomes.MethodsA total of 96 consecutive patients with AIS and 28 age‐ and gender‐matched healthy controls were recruited. Peripheral blood samples were collected, and the percentages of lymphocyte subsets were analyzed by flow cytometry. The dynamic changes in lymphocyte subsets and their correlation with clinical parameters, such as National Institutes of Health Stroke Scale (NIHSS) scores at onset and modified Rankin scale (mRS) scores 3 months later, were evaluated.ResultsIn our study, we observed a decrease in the percentages of T‐lymphocytes (T cells), helper/inducible T‐lymphocytes (Th cells) and suppressor/cytotoxic T‐lymphocytes (Ts cells) in AIS patients as compared to controls. The frequencies of T cells and Ts cells on day 8–14 after stroke in NIHSS ≤4 group were significantly higher than those in NIHSS >4 group. The percentages of T cells and Th cells on day 1–3 after stroke in the mRS ≤2 group were higher than those in the mRS >2 group.ConclusionThe frequencies of T cells, Th cells, and Ts cells in AIS are declined dramatically at least 14 days after stroke. Lower frequencies of T cells and Ts cells on day 8–14 after stroke represent more severe disease conditions, and the percentages of T cells and Th cells within 72 hr after stroke are negatively correlated with 3‐month outcomes, which might have a potential for predicting long‐term prognosis of stroke.

Increased Serum Interleukin-2 Levels Are Associated with Abnormal Peripheral Blood Natural Killer Cell Levels in Patients with Active Rheumatoid Arthritis.

Objective To investigate the relationship between serum interleukin-2 (IL-2) levels and disease activity, absolute numbers of peripheral lymphocyte subsets, autoantibodies, and associated cytokines in patients with rheumatoid arthritis (RA). Methods This study included 106 patients with RA, evaluated their disease activity (DAS28 score), and divided them into disease remission (DAS28 ≤ 2.6), low disease activity (DAS28 ≤ 3.2), and moderate-high disease activity (DAS28 > 3.2) groups. Flow cytometry was used to detect the absolute numbers of peripheral lymphocyte subpopulations and CD4+ T cell subsets in each group, and serum cytokine levels were measured using cytometric bead array. Results Serum IL-2 levels in RA patients were positively correlated with disease activity and rheumatoid factor titers (p < 0.001 and p = 0.045, respectively), and multiple regression analysis revealed that serum IL-2 levels were an independent factor affecting disease activity. Serum IL-2 levels were positively correlated with Th17/Treg ratios (p = 0.013). Compared with the remission group, peripheral lymphocyte and CD4+ T lymphocyte subsets in patients with active RA decreased to varying degrees; however, the numbers of peripheral natural killer (NK) cells were significantly higher in the moderate-high disease activity group than in the remission (p = 0.046) and low disease activity (p = 0.020) groups; the percentages of NK cells had the same trend. In addition, the number and percentage of NK cells were positively correlated with serum IL-2 levels (p = 0.018 and p = 0.006, respectively). Conclusions In RA patients, serum IL-2 levels were not only correlated with patients' disease activity and autoantibody levels but were also involved in their Th17/Treg immune imbalance. In addition, in patients with active RA, NK cell levels were abnormally elevated, possibly due to high serum levels of IL-2.

Impact of radiotherapy on circulating lymphocyte subsets in patients with esophageal cancer.

Radiotherapy (RT) can affect the immune function of patients with cancer. The purpose of this study was to investigate the effect of RT on lymphocyte and its subsets in patients with esophageal cancer (EC).All patients received RT with a mean dose of 5369 cGy (gray). Blood parameters were measured in 31 patients on 3 occasions (before, at the end of radiotherapy, and at 3 months follow-up). The whole blood count and lymphocyte subsets were measured and correlated with short time efficiency and radiation dose parameters.White blood count (WBC) and lymphocyte count (ALC) were greatly decreased at the end of radiotherapy, and the percentages of CD3+, CD3+CD8+ T cells were significantly increased, on the other hand, a decrease in the CD4/CD8 ratio was observed. The percentages of CD3-CD16/56+NK cells and CD19+ B cell were decreased at the end of RT compared with prior RT. The percentages of CD3+ T cells before RT and the WBC and ALC count after RT can be used as prognostic indicators for survival. The PTV dose can cause significant changes in lymphocytes count after RT. CD3+T cells after RT were significantly correlated with mean heart dose and heart V50.Our study identified that RT causes changes in lymphocyte subsets, and these changes may indicate differences in immune function between individuals. Radiotherapy plan should be designed to minimize normal tissue dose to reduce the impact on WBC and lymphocytes.

Characteristics of inflammatory factors and lymphocyte subsets in patients with severe COVID-19.

To investigate the inflammatory factors and lymphocyte subsets which play an important role in the course of severe coronavirus disease 2019 (COVID‐19). A total of 27 patients with severe COVID‐19 who were admitted to Tongji Hospital in Wuhan from 1 to 21 February 2020 were recruited to the study. The characteristics of interleukin‐1β (IL‐1β), IL‐2 receptor (IL‐2R), IL‐6, IL‐8, IL‐10, tumor necrosis factor‐α (TNF)‐α, C‐reactive protein (CRP), serum ferritin and procalcitonin (PCT), and lymphocyte subsets of these patients were retrospectively compared before and after treatment. Before treatment, there was no significant difference in most inflammatory factors (IL‐1β, IL‐2R, IL‐6, IL‐8, IL‐10, CRP, and serum ferritin) between male and female patients. Levels of IL‐2R, IL‐6, TNF‐α, and CRP decreased significantly after treatment, followed by IL‐8, IL‐10, and PCT. Serum ferritin was increased in all patients before treatment but did not decrease significantly after treatment. IL‐1β was normal in most patients before treatment. Lymphopenia was common among these patients with severe COVID‐19. Analysis of lymphocyte subsets showed that CD4+ and particularly CD8+ T lymphocytes increased significantly after treatment. However, B lymphocytes and natural killer cells showed no significant changes after treatment. A pro‐inflammatory response and decreased level of T lymphocytes were associated with severe COVID‐19.

Clinical characteristics and distribution of peripheral T lymphocyte subsets in patients with schistosomal hepatic diseases in Suzhou City

To investigate the clinical characteristics and the distribution of peripheral blood T lymphocyte sub-sets in patients with schistosomal hepatic cirrhosis in Suzhou City. A total of 32 inpatients with liver diseases due to advanced schistosomiasis at the Department of Infectious Diseases, The First Affiliated Hospital of Soochow University from January 2016 to January 2018 were recruited and assigned into the infection and non-infection groups according to presence of co-infections, and 20 old healthy volunteers served as controls. Venous blood samples were collected on the day of admission, and the proportions of CD4+ T cells, CD8+ T cells, regulatory T (Treg) cells and Th17 cells were detected in peripheral blood using flow cytometry. Most patients with liver disorders due to advanced schistosomiasis were admitted to hospital in Suzhou City because of portal hypertension-associated complications, with a high prevalence of co-infections (59.38%, 19/32). The proportions of peripheral CD4+ and CD8+ T cells and Th17 cells were all significantly lower in patients with liver disorders due to advanced schistosomiasis than in controls (t = -5.111, -4.470 and -2.749, all P < 0.05), and a higher proportion of Treg cells was detected in patients than in controls (t = 5.628, P < 0.05). In addition, there were significant differences among the infection group, non-infection group and controls in terms of the percentage of CD4+ T cells, CD8+ T cells, Th17 cells and Treg cells (F = 15.837, 16.594, 9.290 and 27.866, all P < 0.05). Portal hypertension-associated complications are predominantly seen in patients with liver diseases due to advanced schistosomiasis at admission in Suzhou City, and co-infections are common. Imbalance of peripheral T cell subsets is detected in patients with liver diseases due to advanced schistosomiasis in Suzhou City.

Effect of acupoint application on T lymphocyte subsets in patients with chronic obstructive pulmonary disease: A meta-analysis.

The development of chronic obstructive pulmonary disease (COPD) is related to the T lymphocyte mediated inflammatory immune response and immune imbalance. The purpose of this systematic review was to evaluate the clinical efficacy and safety of acupoint application on T lymphocyte subsets in patients with COPD. We searched CNKI, Wan fang, Chongqing VIP, China Biology Medicine disc, PubMed, the Cochrane Library, and EMBASE for studies published as of Oct. 31, 2019. All randomized controlled trials of acupoint application on COPD patients that met the inclusion criteria were included. The Cochrane bias risk assessment tool was used for literature evaluation. RevMan5.3 software was used for meta-analysis. Eight studies (combined n = 524) qualified based on the inclusion criteria. Compared with routine treatment alone, acupoint application combined with routine treatment can significantly increase the T lymphocyte CD4/CD8 ratio (MD 0.12, 95% CI 0.03-0.21, P < .01, I = 49%), reduce CD8 T-cells (MD-0.99, 95% CI-1.70-0.28, P < .001, I = 37%), reduce the times of acute exacerbations (MD-0.28, 95% CI-0.35-0.21, P < .001, I = 0), and improve the clinical efficacy (MD 1.30, 95% CI 1.14-1.48, P < .001, I = 39%). Acupoint application can improve the CD4/CD8 ratio and CD8 T-cells in patients with COPD and has an auxiliary effect in reducing the times of acute exacerbations and improving clinical efficacy.

Effect of dimethyl fumarate on lymphocyte subsets in patients with relapsing multiple sclerosis.

BackgroundIn patients treated with dimethyl fumarate, absolute lymphocyte count decline typically occurs during the first year and then plateaus; early drops have been associated with the development of severe prolonged lymphopenia.ObjectiveWe investigated the effect of dimethyl fumarate on absolute lymphocyte counts and CD4+/CD8+ T cells in patients with relapsing–remitting multiple sclerosis treated with dimethyl fumarate in routine practice.MethodsLymphocyte data were collected via medical chart abstraction. Primary endpoint: change from baseline in absolute lymphocyte count and CD4+/CD8+ counts at 6‐month intervals following dimethyl fumarate initiation.ResultsCharts of 483 patients were abstracted and 476 patients included in the analysis. Mean baseline absolute lymphocyte count (2.23 × 109/l) decreased by ∼39% (95% confidence interval: –41.1 to –37.2) by month 6 and 44% (95% confidence interval: –46.6 to –42.1) by month 12. CD4+ and CD8+ T-cell subsets strongly correlated with absolute lymphocyte count, with greater decreases from baseline to 6 months vs 6–12 months, and in CD8+ vs CD4+ T cells. Prior natalizumab was not a risk factor for lymphopenia.ConclusionDimethyl fumarate-associated decline in absolute lymphocyte count in the first 12 months correlated with decline in CD4+ and CD8+ T cells and was independent of prior natalizumab. Absolute lymphocyte count monitoring continues to be an effective strategy to identify patients at risk of prolonged lymphopenia.

The COVID-19 pandemic and the use of MS disease-modifying therapies

The COVID-19 pandemic and the use of MS disease-modifying therapies

Characteristics and prognostic value of peripheral blood T lymphocyte subsets in patients with severe influenza

Objective: To investigate the characteristics and prognostic value of peripheral blood T lymphocyte subsets in patients with severe influenza. Methods: This was a single-center cross-sectional study in influenza patients admitted to Peking Union Medical College Hospital from August 2017 to April 2018. Peripheral blood lymphocyte subsets were detected by flow cytometry in both patients and 108 healthy controls. Influenza patients were divided into mild group and severe group. Severe patients were further classified into alive and fatal subgroups. Results: A total of 42 influenza patients were recruited in this study, including 24 severe cases (6 deaths). The remaining 18 cases were mild. The peripheral blood lymphocyte counts and lymphocyte subset counts (B, NK, CD4(+)T, CD8(+)T) in either mild patients[795 (571,1 007), 43 (23,144), 70 (47,135), 330 (256,457), 226 (148,366) cells/μl respectively] or severe patients[661 (474,1 151),92 (52,139), 54 (34,134), 373 (235,555), 180 (105,310) cells/μl respectively] were both significantly lower than those of healthy controls [1 963 (1 603,2 394),179 (119,239), 356 (231,496), 663 (531,824), 481 (341,693) cells/μl respectively]. Meanwhile, the T cells and CD8(+)T counts in fatal patients [370 (260,537) cells/μl and 87 (74,105) cells/μl] were significantly lower than those in severe and alive patients [722 (390,990) cells/μl and 222 (154,404) cells/μl]. CD8(+)HLA-DR/CD8(+)and CD8(+)CD38(+)/CD8(+)T cell activating subgroups in mild cases[(53.7±19.2)% and 74.8% (64.1%,83.7%) respectively] were significantly higher than those in severe cases[(38.5±21.7)% and 53.3% (45.3%,67.2%) respectively].Moreover,CD8(+)HLA-DR/CD8(+)count in severe and alive group was higher than that in fatal group [(46.1±19.1)% vs. (18.2±14.6)%, P<0.01]. Logistic regression analysis showed that CD8(+)T cell count (OR=0.952, 95%CI 0.910-0.997, P=0.035) and CD8(+)HLA-DR/CD8(+)T (OR=0.916, 95%CI 0.850-0.987, P=0.022) were both negatively correlated with mortality.Peripheral blood lymphocyte counts in mild cases rapidly decreased within 1 day after diagnosis, and returned to the basic level one week later. Conclusions: All peripheral blood lymphocyte subsets (T,B,NK) in patients with influenza are significantly reduced. These findings are consistent with the immunological characteristics of respiratory viral infections, in which peripheral lymphocytes (especially T cells) migrate to respiratory tract in the early stage and circulate to the peripheral blood after recovery. The activated CD8(+)T cell counts in peripheral blood are negatively correlated with the severity of disease, which could be considered as a prognostic indicator of severe influenza.

Association Between Response to Nivolumab Treatment and Peripheral Blood Lymphocyte Subsets in Patients With Non-small Cell Lung Cancer.

Immune checkpoint blockade represents a major breakthrough in advanced non-small cell lung cancer (NSCLC) therapy. However, success is limited to a subset of patients and there is a critical need to identify robust biomarkers associated with clinical response. In this study, we assessed whether pre-existing immunological characteristics, as well as immune parameters measured during treatment, might provide such clinical guidance. We studied blood samples collected at baseline and during treatment in a cohort of advanced NSCLC patients (n = 74) treated with nivolumab. Several lymphocyte subsets and biomarkers were then correlated with overall survival (OS) as well as clinical response, assessed using RECIST criteria. We found that patients characterized by longer OS had higher levels of CD3+, CD4+, and CD8+ T cells but lower levels of NK cells at baseline. Moreover, that they displayed a statistically significant lower expression of PD-1 on both CD3+ and CD8+ T cells (p = 0.013 and p = 0.033, respectively). The pre-treatment level of exhausted T cells (CD8+PD1+Eomes+) was significantly lower in patients with controlled disease (CD), defined as partial response (PR), and stable disease (SD), compared to those with progressive disease (PD) (p = 0.046). In CD patients, the frequency of exhausted CD8+ T cells further decreased during treatment cycles (p = <0.0001, p = 0.0032, and p = 0.0239, respectively). In conclusion, our results suggest that the distribution of lymphocyte subsets and expression of PD-1 on T cells before treatment may help predict the outcome of anti-PD-1 treatment in NSCLC patients. In addition, assessing the initial levels of exhausted T cells as well as their decrease upon treatment may also predict response and clinical outcome.

The Relationship Between Thyroid Function and T Lymphocyte Subsets in Patients with Hashimoto&amp;apos;s Thyroiditis

<i>Objective</i>: To assess the relationship between thyroid function and T lymphocyte subsets in Patients with Hashimoto's Thyroiditis. <i>Method</i>: To select 131 diagnosed HT patients as the research object, which is divided into HT hyperthyroidism group (Group A) with 18 cases, normal HT thyroid function group (Group B) with 35 cases, HT subclinical hypothyroidism group (Group C) with 42 cases, and HT hypothyroidism group (Group D) with 36 cases in accordance with thyroid function. Besides, 40 cases of healthy check-up people are selected as the control group. ECLIA is adopted to test the thyroid function index of each group, and FCM is adopted to test T lymphocyte subsets. <i>Result</i>: Compare CD3⁺T lymphocytes of each group, Group D is obviously higher than Group A, Group B, and the control group, and the difference has statistic significance (P<0.05); Compare CD3⁺CD4⁺T lymphocyte and CD4⁺/CD8⁺ of each group, Group D is obviously higher than other groups, Group C is obviously higher than Group A, Group B, and the control group, Group A and Group B are obviously higher than the control group, and the differences have statistic significance (P<0.05); Compare CD3⁺CD8⁺T lymphocytes of each group, Group D is obviously lower than other groups, Group C is obviously lower than Group A, Group B, and the control group, the difference has statistic significance (P<0.05). The correlation analysis shows that TSH is in positive correlation with CD4⁺/CD8⁺, FT3 is in positive correlation with CD3⁺CD8⁺T, and FT4 is in positive correlation with CD3⁺CD8⁺T and in negative correlation with CD4⁺/CD8⁺. <i>Conclusion</i>: HT patients have the imbalance of T lymphocyte subsets, and the T lymphocyte subsets ratio of HT patients of different thyroid function has obvious differences, which may have close relationship with the occurrence and development of HT.