Peripheral Lymphocyte Changes Associate With the Progression of Necrotizing Enterocolitis in Infants.

INTRODUCTION: Immune factors are important antecedents in the pathophysiology of necrotizing enterocolitis (NEC). However, studies on the peripheral blood lymphocyte subsets changes in NEC patients among different Bell stages and in patients requiring surgery are scarce. METHODS: 34 infants with NEC and 33 age-matched controls were included. Peripheral blood was collected within 48 h after NEC diagnosis. Peripheral blood B and T lymphocytes subsets were detected by 12-color flow cytometry. Cell ratios were calculated, and their relationship to disease severity and their roles as indicators for surgery were assessed. RESULTS: NEC patients showed elevated percentages of unSwB cells (CD27+IgD+ unswitched memory/activated B cells)/B cells, SwB cells (CD27+IgD-switched memory B cells)/B cells, CD8+ T (CD3+CD8+ T cells)/T cells, Tem (CD45RA-CCR7-effector memory T cells)/CD4+ T cells, Tem/CD8+ T cells and decreased Bn (CD27-IgD+ naïve B cells)/B cells, CD4+T (CD3+CD4+ T cells)/T cells, CD45RA+ CCR7+ naïve T cells (CD45RA+CCR7+ naïve T cells)/CD8+T cells. Compared to NEC patients at BELL stage I + II, patients at BELL stage III showed increased percentages of SwB cells/B cells, antibody secreting cell (ASC, CD3-CD20-CD27high CD38high ASCs)/B cells and Tem/CD4+ T cells, and decreased percentages of CD45RA+CCR7+ naïve T cells/CD4+ T cells. The Receiver Operating Characteristic Curve analysis showed that the sensitivity of ASC/B cells ratio (0.52%) is 86.67% and the specificity of Tem/CD4+T ratio (5.22%) is 100%, indicating that NEC patients required surgery. CONCLUSIONS: The severity of NEC exhibits codirectional changes with the maturation of B and T lymphocytes, especially CD4+ T cells. The increased ASC/B and Tem/CD4+ T cells could serve as potential indicators for NEC patients requiring surgery.

Differential peripheral memory T cell subsets sensitively indicate the severity of nonalcoholic fatty liver disease.

AIM: Differential patterns of peripheral memory T cell subsets in nonalcoholic fatty liver disease (NAFLD) were assessed using flow cytometry (FCM) to elucidate their association with NAFLD severity and provide a new noninvasive method to sensitively detect the disease severity in addition to existing biomarkers. METHODS: We assessed the differential frequencies of peripheral memory T cell subsets in 103 patients with NAFLD according to the degree of liver fibrosis (FIB) using FCM analysis. We focused on the following populations: CCR7+ CD45RA+ naïve T, CCR7+ CD45RA- central memory T cells (TCM), CCR7- CD45RA- effector memory T, and CCR7- CD45RA+ terminally differentiated effector memory T (TEMRA) cells in CD4+ and CD8+ T, Th1, Th2, and Th17 cells, respectively. To evaluate the pathological progression of the disease, these frequencies were also examined according to the degree of the NAFLD activity score (NAS). RESULTS: Several significant correlations were observed between laboratory parameters and peripheral memory T lymphocyte frequencies according to the degree of liver FIB and NAS in NAFLD. In univariate and multivariate analyses, the frequency of CD8+ TEMRA cells predicted severe FIB, and the predictive power was validated in an independent cohort. Furthermore, the frequencies of several memory T cell subsets sensitively indicated the pathological progression of NAFLD (Th17 TCM: steatosis, CD4+ TCM: lobular inflammation, and CD8+ TEMRA and effector memory T cells: hepatocellular ballooning). CONCLUSIONS: Our results suggest that the analysis of peripheral memory T lymphocyte frequencies can noninvasively predict severe FIB and sensitively indicate the pathological progression of NAFLD.

Development and validation of a clinic machine-learning nomogram for the prediction of risk stratifications of prostate cancer based on functional subsets of peripheral lymphocyte.

BACKGROUND: Non-invasive risk stratification contributes to the precise treatment of prostate cancer (PCa). In previous studies, lymphocyte subsets were used to differentiate between low-/intermediate-risk and high-risk PCa, with limited clinical value and poor interpretability. Based on functional subsets of peripheral lymphocyte with the largest sample size to date, this study aims to construct an easy-to-use and robust nomogram to guide the tripartite risk stratifications for PCa. METHODS: We retrospectively collected data from 2039 PCa and benign prostate disease (BPD) patients with 42 clinical characteristics on functional subsets of peripheral lymphocyte. After quality control and feature selection, clinical data with the optimal feature subset were utilized for the 10-fold cross-validation of five Machine Learning (ML) models for the task of predicting low-, intermediate- and high-risk stratification of PCa. Then, a novel clinic-ML nomogram was constructed using probabilistic predictions of the trained ML models via the combination of a multivariable Ordinal Logistic Regression analysis and the proposed feature mapping algorithm. RESULTS: 197 PCa patients, including 56 BPD, were enrolled in the study. An optimal subset with nine clinical features was selected. Compared with the best ML model and the clinic nomogram, the clinic-ML nomogram achieved the superior performance with a sensitivity of 0.713 (95% CI 0.573-0.853), specificity of 0.869 (95% CI 0.764-0.974), F1 of 0.699 (95% CI 0.557-0.841), and AUC of 0.864 (95% CI 0.794-0.935). The calibration curve and Decision Curve Analysis (DCA) indicated the predictive capacity and net benefits of the clinic-ML nomogram were improved. CONCLUSION: Combining the interpretability and simplicity of a nomogram with the efficacy and robustness of ML models, the proposed clinic-ML nomogram can serve as an insight tool for preoperative assessment of PCa risk stratifications, and could provide essential information for the individual diagnosis and treatment in PCa patients.

Peripheral blood lymphocytes influence human papillomavirus infection and clearance: a retrospective cohort study.

BACKGROUND: There is a close correlation between HPV infection and systemic immune status. The purpose of this study was to determine which lymphocytes in peripheral blood influence human papillomavirus (HPV) infection and to identify whether peripheral blood lymphocyte (PBL) subsets could be used as biomarkers to predict HPV clearance in the short term. METHODS: This study involved 716 women undergoing colposcopy from 2019 to 2021. Logistic and Cox regression were used to analyze the association of PBLs with HPV infection and clearance. Using Cox regression, bidirectional stepwise regression and the Akaike information criterion (AIC), lymphocyte prediction models were developed, with the C-index assessing performance. ROC analysis determined optimal cutoff values, and their accuracy for HPV clearance risk stratification was evaluated via Kaplan‒Meier and time-dependent ROC. Bootstrap resampling validated the model and cutoff values. RESULTS: Lower CD4 + T cells were associated with a higher risk of HPV, high-risk HPV, HPV18 and HPV52 infections, with corresponding ORs (95% CI) of 1.58 (1.16-2.15), 1.71 (1.23-2.36), 2.37 (1.12-5.02), and 3.67 (1.78-7.54), respectively. PBL subsets mainly affect the natural clearance of HPV, but their impact on postoperative HPV outcomes is not significant (P > 0.05). Lower T-cell and CD8 + T-cell counts, as well as a higher NK cell count, are unfavorable factors for natural HPV clearance (P < 0.05). The optimal cutoff values determined by the PBL prognostic model (T-cell percentage: 67.39%, NK cell percentage: 22.65%, CD8 + T-cell model risk score: 0.95) can effectively divide the population into high-risk and low-risk groups, accurately predicting the natural clearance of HPV. After internal validation with bootstrap resampling, the above conclusions still hold. CONCLUSIONS: CD4 + T cells were important determinants of HPV infection. T cells, NK cells, and CD8 + T cells can serve as potential biomarkers for predicting natural HPV clearance, which can aid in patient risk stratification, individualized treatment, and follow-up management.

Characteristics of peripheral lymphocyte subsets in patients with different stages of schistosomiasis japonica.

Immune cells are important for the development of schistosomiasis japonica and are also critical for the treatment of schistosomiasis. The immune cells in the peripheral blood help assess the immune state. The peripheral lymphocytes in schistosomiasis mansoni were well studied; however, immune cells in patients with different stages of schistosomiasis japonica are not well analysed. Here, we performed a preliminary study to explore characteristics of peripheral lymphocyte subsets in patients with different stages of schistosomiasis japonica. 135 patients with Schistosoma japonicum infection and 25 healthy volunteers were included in this study, including 84 patients with chronic S. japonicum infection and 51 patients with advanced S. japonicum infection. Flow cytometry analysis was performed to evaluate peripheral lymphocytes including T cells, B cells, and natural killer (NK) cells. Blood routine and liver function test data were analysed. Ultrasound examination was used to access liver fibrosis according to the World Health Organization standard about ultrasound in schistosomiasis. Demographic data analysis suggested there was no difference in age and gender in patients with S. japonicum infection and health control group. Liver function tests showed that patients with advanced schistosomiasis had a higher incidence of liver function abnormality and blood lipid than those with chronic schistosomiasis. Blood routine results reflected that haemoglobin, red blood cells, platelets, as well as lymphocytes in the advanced group were significantly less than that in the chronic group. Furthermore, flow cytometry analysis indicated that the percentage of CD4+ T cells was lower in the advanced group, but the percentage of CD19+ B cells was higher in the advanced group. In addition, the number of CD3+ T cells, CD3+ CD4+ T cells, CD3+ CD8+ T cells, and NK cells was less in the advanced group when compared with those in the chronic group. In addition, there was a correlation between the decrease in CD4+ T cells and more severe fibrosis on ultrasound images. Our results indicated that the immune state in the peripheral is different in different stages of S. japonicum infection. Lymphocyte subset analysis has potential to facilitate differential diagnosis of different stages of schistosomiasis japonica and even to be a prognostic factor.

Dynamic Changes of Peripheral NK Cells Predict Outcome in Patients with PD-L1 Positive Non-small-cell Lung Cancer Undergoing Immune Checkpoint Inhibitors as Second-line Therapy.

We evaluated immune cell frequencies in peripheral blood samples of 41 NSCLC patients before and after second-line therapy with anti-PD-1/PD-L1 agents. Changes in lymphocyte subsets and their correlation with clinical response, progression-free survival (PFS), and overall survival (OS) were analyzed. We observed an increase in median values of all lymphocyte subsets, being significant only for NK cells. A correlation was retrieved between higher post-treatment NK cell level and clinical benefit. On multivariate analysis, PD-L1 tumor proportion score ≥1% and higher post-treatment NK cell counts were predictive of longer PFS and OS. Co-presence of these factors was characterized by longer survival.

Effect on the expression of drd2 and drd3 after neonatal lesion in the lymphocytes, nucleus accumbens, hippocampus and prefrontal cortex: comparative analysis between juvenile and adult Wistar rats.

BACKGROUND: Neonatal lesion in the ventral hippocampus (NLVH) is a validated animal model to study schizophrenia from a neurodevelopmental perspective. This animal model is also used to investigate how neonatal lesions may alter the genetic expression of dopaminergic receptors. The present study compares mRNA expression levels of dopamine receptors (drd2 and drd3) in lymphocytes and brain of NLVH animals at two different age stages: young and adult. METHODS: The NLVH procedure was performed on 20 male Wistar rats at postnatal days 5-7. The mRNA expression levels of drd2 and drd3 genes in lymphocytes, nucleus accumbens, hippocampus and prefrontal cortex were measured and analyzed at postnatal days 45 and 90. The results were compared and contrasted with respective sham groups. RESULTS: In lymphocytes, only in NLVH-adult group we observed drd2 mRNA expression, while drd2 mRNA expression was not observed in the NLVH-juvenile rats; on the other hand, the drd3 mRNA expression did not show significant statistical differences. In hippocampus no differences were observed between drd2 mRNA or drd3 mRNA expression when comparing juvenile/adult shams with NLVH groups. In the prefrontal area, a decrease in drd2 mRNA expression levels were observed in the NLVH-adult group (F(1,3) = 52.83, p = 0,005) in comparison to the sham-adult group. Finally, in the nucleus accumbens, a strong decrease of drd3 mRNA expression was observed in the NLVH-adult group in comparison to the sham-adult group (F(1,3) = 123,2, p < 0.001). CONCLUSIONS: Our results show that differences in drd2 and drd3 mRNA levels in NLVH-adults are patent when compared to the sham-adult group or with the NLVH-juvenile group. These findings suggest that the expression levels may be regulated during adulthood, leading to behavioral and neurochemical changes related to schizophrenia. Therefore, more studies are necessary to determine the role of dopamine receptors as possible molecular markers for neurodevelopmental changes associated with schizophrenia.

Abnormal distribution of peripheral lymphocyte subsets induced by PDAC modulates overall survival.

BACKGROUND/OBJECTIVES: The impairment of the immune system is prevalent in patients with malignancies, including pancreatic ductal adenocarcinoma (PDAC). The present study aimed to evaluate alternations of peripheral lymphocyte subsets in patients with PDAC, and also to assess the prognostic value of observed changes. METHODS: We recruited 160 consecutive PDAC patients who had undergone radical surgical resection between 2010 and 2013. To investigate the prognostic factors, we detected the peripheral lymphocyte subsets in PDAC by flow cytometry, including T cells (CD3(+), CD3(+)CD4(+), CD3(+)CD8(+), CD8(+)CD28(+)), regulatory T cells (Tregs, CD4(+)CD25(+)CD127(-)), natural killer cells (NK cells, CD3(-)CD56(+)) and B cells (CD19(+)). We also evaluated the clinical and pathological features of these patients. Survival analysis was performed by univariate and multivariate analyses. RESULTS: Our results indicated the profile of peripheral lymphocyte subsets undergone profound changes in PDAC patients. Univariate and multivariate analysis indicated the levels of peripheral lymphocyte subsets (CD19(+) B cells, Tregs and CD8(+)CD28(+) T cells) were independent predictors for overall survival. The results also suggested that the systemic impairment of immune system in patients with PDAC, was reversed when primary tumor was removed. CONCLUSIONS: The present study provided some evidences that the impairment of host immunity induced by PDAC may play a role in the survival of patients.

Dynamic change of lymphocytes associated with short-term prognosis in anti-MDA5-positive dermatomyositis with interstitial lung disease: a multicenter retrospective study.

Lymphopenia is a unique manifestation of anti-MDA5 positive dermatomyositis with interstitial lung disease (MDA5 + DM-ILD). This study aimed to investigate the relationship between dynamic changes in peripheral lymphocytes and short-term prognosis in patients of MDA5 + DM-ILD. Two hundred sixty-three MDA5 + DM-ILD patients were divided into different groups according to lymphocyte count and death or survival within 1 month, then the differences in clinical features and outcomes were compared. Associations between lymphocytes and risk of death within 1 month were also investigated in different lymphocyte groups using Cox proportional hazard models. A generalized additive mixed model (GAMM) was established to analyze the dynamic changes of lymphocytes in the death 1-month group. Lymphocytes of the patients who died within 1 month were significantly lower than survivors by different lymphocyte grouping methods, and the total lymphocytes showed a gradually decreasing trend in non-survivors. And the difference between survivors and non-survivors was more obvious over time. The lowest tertile of baseline lymphocytes as a reference, the hazard ratios for death within 1 month in the highest tertile were 0.497 (95% CI 0.26-0.949, P for trend = 0.033) after adjustment for potential confounders. GAMM analysis found a mean daily decrease of lymphocytes (0.034 × 10^9/L) after admission in death 1-month patients. Low baseline lymphocytes and gradually declined lymphocytes are both associated with a high risk of death within 1 month. However dynamic changes in lymphocytes can better reflect the disease status and better predict the short-term prognosis than baseline lymphocytes in MDA5 + DM-ILD patients. Key points •Low baseline lymphocytes and gradually decreased trend along time correlated with poor short-term prognosis in MDA5 + DM-ILD patients. •Dynamic changes of lymphocytes can better reflect the disease status and better predict the 1-month prognosis than baseline lymphocytes in MDA5 + DM-ILD patients. •Generalized additive mixed model (GAMM) analysis found that in 1-month non-survivors, peripheral blood lymphocytes decreased by 0.034 × 10^9/L per day, while the lymphocytes in survivors gradually increased.

Comparison of Postoperative Results With Prognostic Nutritional Index for Lumbar Disc Herniation.

INTRODUCTION: The prognostic nutritional index (PNI) is an immune-nutritional index simply provided by a blood test. We retrospectively compared the postoperative outcomes of patients with lumbar disc herniation divided into two groups according to the PNI. MATERIALS AND METHODS: Seventy-three patients who underwent surgery at our hospital were included in the study. All patients had herniation between one of the L3/4, L4/5, or L5/S intervertebral discs and underwent one posterior lumbar interbody fusion. These patients were divided into two groups: patients with a PNI of <50 (poorly nourished (PN) group) and patients with a PNI of ≥50 (well-nourished (WN) group). Evaluation items included patient background characteristics, operative time, blood loss, postoperative complications, and length of hospital stay. RESULTS: The results showed that the body mass index was significantly higher in the WN group than in the PN group (p=0.0221). The rates of collagen disease, steroid use, and postoperative complications were significantly higher (p=0.0475, p=0.0073, and p=0.0211, respectively) and the length of hospital stay was significantly longer (p=0.021) in the PN group than in the WN group. CONCLUSION: In conclusion, this study indicates that postoperative complications and the length of hospital stay are significantly worse in PN patients than in WN patients.

Expression characteristics of peripheral lymphocyte programmed death 1 and FoxP3+ Tregs in gastric cancer during surgery and chemotherapy.

BACKGROUND: Programmed death 1 (PD-1) and CD4+CD25+FoxP3+ expression in peripheral blood T-cells has been previously reported in various types of cancer. However, the specific variation tendency during surgery and chemotherapy, as well as their relationship in gastric cancer patients, still remain unclear. Understanding this aspect may provide some novel insights for future studies on tumor recurrence and tumor immune escape, and also serve as a reference for determining the optimal timing and dose of clinical anti-PD-1 antibodies. AIM: To observe and analyze the expression characteristics of peripheral lymphocyte PD-1 and FoxP3+ regulatory T cells (FoxP3+ Tregs) before and after surgery or chemotherapy in gastric cancer patients. METHODS: Twenty-nine stomach cancer patients undergoing chemotherapy after a D2 gastrectomy provided 10 mL peripheral blood samples at each phase of the perioperative period and during chemotherapy. This study also included 29 age-matched healthy donors as a control group. PD-1 expression was detected on lymphocytes, including CD4+CD8+CD45RO+, CD4+CD45RO+, and CD8+CD45RO+ lymphocytes as well as regulatory T cells. RESULTS: We observed a significant increase of PD-1 expression on immune subsets and a larger number of FoxP3+ Tregs in gastric cancer patients (P < 0.05). Following D2 gastrectomy, peripheral lymphocytes PD-1 expression and the number of FoxP3+ Tregs notably decrease (P < 0.05). However, during postoperative chemotherapy, we only observed a decrease in PD-1 expression on lymphocytes in the CD8+CD45RO+ and CD8+CD45RO+ populations. Additionally, linear correlation analysis indicated a positive correlation between PD-1 expression and the number of CD4+CD45RO+FoxP3high activated Tregs (aTregs) on the total peripheral lymphocytes (r = 0.5622, P < 0.0001). CONCLUSION: The observed alterations in PD-1 expression and the activation of regulatory T cells during gastric cancer treatment may offer novel insights for future investigations into tumor immune evasion and the clinical application of anti-PD-1 antibodies in gastric cancer.

CD19 (+) B Cell Combined with Prognostic Nutritional Index Predicts the Clinical Outcomes of Patients with Gastric Cancer Who Underwent Surgery.

(1) Background: The aim of this study was to explore the predictive ability of lymphocyte subsets for the prognosis of gastric cancer patients who underwent surgery and the prognostic value of CD19 (+) B cell combined with the Prognostic Nutritional Index (PNI). (2) Methods: This study involved 291 patients with gastric cancer who underwent surgery at our institution between January 2016 and December 2017. All patients had complete clinical data and peripheral lymphocyte subsets. Differences in clinical and pathological characteristics were examined using the Chi-square test or independent sample t-tests. The difference in survival was evaluated using Kaplan-Meier survival curves and the Log-rank test. Cox's regression analysis was performed to identify independent prognostic indicators, and nomograms were used to predict survival probabilities. (3) Results: Patients were categorized into three groups based on their CD19 (+) B cell and PNI levels, with 56 cases in group one, 190 cases in group two, and 45 cases in group three. Patients in group one had a shorter progression-free survival (PFS) (HR = 0.444, p < 0.001) and overall survival (OS) (HR = 0.435, p < 0.001). CD19 (+) B cell-PNI had the highest area under the curve (AUC) compared with other indicators, and it was also identified as an independent prognostic factor. Moreover, CD3 (+) T cell, CD3 (+) CD8 (+) T cell, and CD3 (+) CD16 (+) CD56 (+) NK T cell were all negatively correlated with the prognosis, while CD19 (+) B cell was positively associated with the prognosis. The C-index and 95% confidence interval (CI) of nomograms for PFS and OS were 0.772 (0.752-0.833) and 0.773 (0.752-0.835), respectively. (4) Conclusions: Lymphocyte subsets including CD3 (+) T cell, CD3 (+) CD8 (+) T cell, CD3 (+) CD16 (+) CD56 (+) NK T cell, and CD19 (+) B cell were related to the clinical outcomes of patients with gastric cancer who underwent surgery. Additionally, PNI combined with CD19 (+) B cell had higher prognostic value and could be used to identify patients with a high risk of metastasis and recurrence after surgery.

Short-term prognostic role of peripheral lymphocyte subsets in patients with gastric cancer.

BACKGROUND: Immune function is associated with clinical outcomes in patients with gastric cancer. This study aimed to explore the prognostic role of peripheral lymphocyte subsets in patients with gastric cancer after curative surgery. METHODS: This retrospective study was conducted at a single tertiary referral hospital. We included patients diagnosed with gastric cancer who had undergone surgery and met the inclusion criteria. Clinicopathological characteristics and preoperative peripheral lymphocyte subset data were collected for the analysis. Recurrence-free survival (RFS) and overall survival were analyzed using the Kaplan-Meier curve and Cox hazard regression model. We used the Whitney test and Spearman test to analyze the correlation between lymphocyte subsets and clinicopathological characteristics. RESULTS: This study included 171 patients with gastric cancer who underwent curative surgery. Multivariate analysis revealed that carcinoembryonic antigen (p < 0.01), carbohydrate antigen 19-9 (p < 0.001), lymph node metastases (p < 0.001), total T-cell count (p = 0.02), B-cell count (p < 0.01), and regulatory T-cell percentage (p < 0.01) were independent predictive factors associated with RFS. CONCLUSIONS: Impaired immune function may lead to early recurrence following curative surgery. Our study showed that the characteristics of peripheral lymphocyte subsets (T, B, and Treg cells) were independent predictive factors for recurrence in patients with gastric cancer after surgery.

Tofacitinib for new-onset adult patients with anti-melanoma differentiation-associated 5 gene antibody positive dermatomyositis.

OBJECTIVE: We aimed to investigate the efficacy and safety of tofacitinib in adult anti-melanoma differentiation-associated 5 gene (Anti-MDA5) antibody-positive dermatomyositis (DM) patients and evaluate the effects of tofacitinib on peripheral lymphocyte subsets. METHODS: An open-label study was conducted of 15 new-onset, untreated adult patients with anti-MDA5-positive DM for tofacitinib with a dose of 5mg twice per day. The primary outcome was defined by the total improvement score after treatment for 6 months, classified according to the 2016 American College of Rheumatology/ European League Against Rheumatism (ACR/EULAR) response criteria for adult DM and polymyositis. Secondary outcomes after 6 months treatment comprised the change in predicted forced vital capacity, the percentage of predicted carbon monoxide diffusion capacity, ferritin level and peripheral blood lymphocyte subsets measured by flow cytometry. RESULTS: Disease responses occurred in 10 patients (71.4%) after 6 months. The median total improvement score was 43.75 (41.875-59.375). Two patients achieved major improvement, seven achieved moderate and one minimal. The serum ferritin level (p = 0.008), DLCO% (p = 0.009) was improved and a marked increase in total lymphocyte cells (p = 0.045) and CD8+ T cells (p = 0.006) was measured after 6 months treatment compared to baseline. CONCLUSION: Tofacitinib demonstrates efficacy for new-onset, untreated adult patients with anti-MDA5-positive DM and stimulates proliferation of peripheral lymphocyte subsets (especially total lymphocyte cells and CD8+ T cells) after 6 months treatment. Further studies are warranted to validate the current findings. Key Points • Treatment of anti-melanoma differentiation-associated 5 gene antibody positive dermatomyositis is always challenging. • This prospective, open-label clinical trial demonstrates tofacitinib is an effective and safe agent for new-onset adult patients with anti-MDA5-positive DM. • Tofacitinib treatment results in an increase in peripheral lymphocyte numbers, especially CD8+ T cells at 6 months compared with pre-treatment levels.

Predictive value of peripheral lymphocyte subsets for the disease progression in patients with sepsis.

OBJECTIVE: To investigate the predictive value of peripheral lymphocyte subsets for sepsis progression. METHODS: Patients with sepsis were divided into the improved group (n = 46) and severe group (n = 39) according to disease progression. Flow cytometric analysis was performed to enumerate absolute counts of peripheral lymphocyte subsets. Logistic regression analyses were conducted to identify clinical factors linked to sepsis progression. RESULTS: The absolute counts of peripheral lymphocyte subsets were markedly decreased in septic patients compared with healthy controls. After treatment, the absolute counts of lymphocytes, CD3+ T cells, and CD8+ T cells were restored in the improved group, and reduced in the severe group. Logistic regression analysis indicated that a low CD8+ T cells count was a risk factor for sepsis progression. Receiver operating characteristic curve analysis revealed that CD8+ T cells count had the greatest ability to predict sepsis progression. CONCLUSIONS: The absolute counts of CD3+ T cells, CD4+ T cells, CD8+ T cells, B cells, and natural killer cells were significantly higher in the improved group than the severe group. CD8+ T cells count was predictive of sepsis progression. Lymphopenia and CD8+ T cells depletion were associated with the clinical outcomes of sepsis, suggesting that CD8+ T cells have potential as a predictive biomarker and therapeutic target for patients with sepsis.

Noninvasive approach to indicate risk factors of nonalcoholic steatohepatitis overlapping autoimmune hepatitis based on peripheral lymphocyte pattern.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) clinically includes autoimmunity as indicated by antinuclear antibody (ANA) positivity and overlap of autoimmune hepatitis (AIH). Discriminating AIH-overlap NASH from NAFLD/NASH is required for proper treatment, and typically involves pathological diagnosis by invasive liver biopsy. Differential patterns of peripheral lymphocytes in NAFLD and AIH were assessed to noninvasively indicate risk factors of AIH-overlap NASH by flow cytometry (FCM). METHODS: We assessed the differential frequencies of peripheral lymphocytes in 115 patients: 70 NASH (ANA negative:positive:AIH-overlap = 36:20:14), 18 NAFL, and 27 AIH (acute:chronic = 12:15) patients diagnosed by FCM. We focused on the following populations of lymphocytes: T cells, B cells, natural killer (NK) cells, NKT cells, helper T cell (Th) subsets (Th1, Th2, and Th17), and regulatory T cells; we also examined programmed cell death (PD) 1 and cytotoxic T-lymphocyte antigen levels. RESULTS: Several significant differences in laboratory parameters and peripheral lymphocyte frequencies were found among the NAFLD and AIH subgroups. In univariate and multivariate analyses, hyaluronic acid level, liver stiffness, and the frequencies of Th17 and CD8+ PD1+ T cells were independent risk factors of NASH in NAFLD. Regarding overlap of AIH, only the frequency of CD8+ PD1+ T cells (odds ratio, 0.01; 95% CI 0.00-38.9, p = 0.004) was an independent risk factor in NASH and significantly decreased in AIH. CONCLUSIONS: The decreased frequency of peripheral CD8+ PD1+ T cells is an independent risk factor of NASH overlapping with AIH in the present cohort. Our findings will facilitate development of a new noninvasive FCM method for indicating risk factors of NASH, including autoimmunity.

Evaluation of peripheral lymphocyte subsets in acne vulgaris patients before and after systemic isotretinoin treatment.

OBJECTIVES: Isotretinoin (ISO) is a retinoic acid-derived molecule which is very efficient in the treatment of acne vulgaris (AV). Little is known regarding alterating affects of systemic ISO on immune system. AND METHODS: Thirty-two patients with moderate and severe AV with indications for systemic ISO treatment were recruited. The evaluation of peripheral blood lymphocyte subsets was made on treatment initiation and at the end of the therapy by flow cytometry. RESULTS: CD16/56+ natural killer (NK) cell levels were higher in patients with severe acne compared to moderate acne (P = 0.009). CD45RA+ (naive) cell levels decreased significantly after systemic ISO treatment; the mean percentage was 66.9 ± 6.5 which decreased to 63.9 ± 7.5 after treatment (P = 0.013). CD19+ cell levels were also significantly increased; mean percentage (%) and absolute cell counts were 8.0 ± 3.1 and 161.3 ± 7.36 cells/µl which increased to 10 ± 2.7 and 227.7 ± 108.7 cells/µl, at the end of treatment, respectively (P = 0.007, P = 0.011). CONCLUSIONS: NK cell count may be a parameter related to acne severity. Systemic ISO may have an inhibitory effect on naïve T cells. Finally, systemic ISO seems to stimulate mature B-cell proliferation.

Pre-operative neutrophil-to-lymphocyte ratio is an independent prognostic factor in patients with gastric cancer.

OBJECTIVE: To evaluate the prognostic significance of peripheral lymphocyte count and its derived inflammatory markers, such as neutrophil-to-lymphocyte ratio (NLR), in a cohort of patients with gastric cancer (GC). METHODS: In this retrospective study, the clinical characteristics and follow-up information, both pre- and post-operative within one week of laboratory findings, of 338 patients with GC who underwent radical gastrectomy were retrieved, and their prognostic significance was evaluated. RESULTS: Both lower pre- and post-operative lymphocyte counts and higher NLR and SSI were significantly related to advanced tumour (pT) and disease stages (American Joint Committee on Cancer [AJCC]) in patients with GC. Log-rank survival analysis showed that, in addition to traditional pT, pN, pM, and AJCC stages, both lower pre- (p = 0.041) and post-operative (p = 0.002) lymphocyte counts and higher NLR (ppre < 0.001 and ppost = 0.008) and SSI (ppre = 0.014 and ppost = 0.145) were associated with worse survival. Cox proportional hazards analysis revealed that pre-operative NLR (p = 0.018; hazard ratio = 1.778) was an independent predictor of prognosis in patients with GC. Moreover, when the pre-operative NLR was divided into NLRlow and NLRhigh, NLRhigh showed stratified prognostic value for patient sex (male, p = 0.001; female, p = 0.044), age (younger, p = 0.005; older, p = 0.005), and AJCC stage III (p = 0.007). CONCLUSION: Pre-operative NLR is an independent prognostic factor for patients with GC and has stratified prognostic value for patients with AJCC stage III GC.

Peripheral Lymphocyte Counts and Lymphocyte-Related Inflammation Indicators During Radiotherapy for Pelvic Malignancies: Temporal Characterization and Dosimetric Predictors.

Purpose: To identify the dosimetric predictors of lymphocytopenia and retrospectively analyze the changing trend of peripheral lymphocyte counts and lymphocyte-related inflammatory indicators in patients with simple pelvic radiotherapy. Methods and Materials: We retrospectively reviewed the clinical data of 188 patients with pelvic malignancies undergoing pelvic radiotherapy. The absolute count of neutrophils, lymphocytes, monocytes, and platelets at each time point was collected, and lymphocyte-related inflammation indicators were obtained, including neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), and the systemic immune-inflammation index (SII). The total pelvic bone (TPB) and the body within the 5 Gy coverage were retrospectively delineated for each patient. Dose-volume histograms corresponding to the delivered volumetric arc therapy plan were used to assess the dose volumes received by the TPB and body. A paired-samples t-test or Wilcoxon signed-rank test for matched pairs was applied for pairwise comparisons. We also established a stepwise multiple linear regression model for the peripheral lymphocyte count (PLC) value at the end of radiotherapy. Results: The PLC and lymphocyte-related inflammatory indicators changed significantly after the start of radiotherapy and persisted for 3-6 months after radiotherapy. The nadirs of PLC occurred at RT-End, and the PLC was still significantly lower than the baseline value at RT-3 months and RT-6 months. NLR, PLR, and SII at RT-End are about 3.5 times the value at RT-Baseline, while LMR is one-fourth of the basal value. In a further multiple stepwise linear regression analysis, the basal PLC (ß = 0.156, p ≤ .001), gender (ß = 0.096, p = .005), and TPB-V5 (ß = -0.016, p ≤ .001) turned out to be the predictor of the absolute value of lymphocytes at the end of radiotherapy. Conclusions: The impact of pelvic radiotherapy on PLC and lymphocyte-related inflammatory indicators is considerable and long-lasting. Minimizing pelvic bone radiation exposure dose (5 Gy) may help to avoid severe cases of lymphocytopenia.

Radioprotective Effect of Rosmarinus officinalis L (Rosemary) Essential Oil on Apoptosis, Necrosis and Mitotic Death of Human Peripheral Lymphocytes (PBMCs).

Background: Rosemary plant, with phenolic compounds, is known as an antioxidant herb and able to scavenge free radical agents in the biological environment; therefore, it is expected that the rosemary essential oil (R-EO) shows the radioprotective effect to protect individuals who are physically in contact with ionizing radiation. Objective: This study aimed to assess the radioprotective effect of R-EO on human peripheral blood mononuclear cells (PBMCs). Material and Methods: In this experimental study, the toxicity of the rosemary essential oil on PBMCs was assessed by the 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide (MTT) assay. The cells were irradiated at 0. 25 and 200 cGy using a 6 MV X-ray linear accelerator. The survival, apoptosis, necrosis, and survival enhancement factors of cells were analyzed by MTT and flow cytometry analyses with a non-toxic concentration of the rosemary essential oil (IC10). Results: Irradiation of cells in the presence of R-EO caused a significant increase in cell survival compared with the control in both 25 and 200 cGy radiation doses. Also, the percentages of apoptosis and necrosis of cells showed a significant decrease compared with the control. Conclusion: Rosemary essential oil as a natural and non-toxic compound could show favorable radioprotective effects in such a way that significantly increases the survival rate and decreases the percentage of apoptosis and necrosis of PBMCs.