Cell Ratio In Peripheral Blood Research Articles

A mechanistic study of radiotherapy on intratumoral NK cell infiltration augmentation by regulating the EZH2/CXCL10 pathway in hepatocellular carcinoma cells

Objective: To investigate the effect and associated mechanism of tumor tissue-infiltrating NK cells after receiving radiotherapy for hepatocellular carcinoma (HCC). Methods: A HCC tumor-bearing mouse model was constructed using human hepatocellular carcinoma cell line (SK-Hep-1) and divided into four groups: control, radiotherapy, NK cell clearance, and NK clearance combined with radiotherapy. Tumor growth condition was simultaneously recorded. The NK cell ratio in peripheral blood and the NK cell intratumoral infiltration condition were detected by flow cytometry and immunohistochemistry. Lentiviral-constructed SK-Hep-1 cells was used to detect the effect of radiotherapy on the regulation of CXCL10 and NK cell chemotaxis following EZH2 overexpression. SK-Hep-1 cells were irradiated in vitro and in vivo. The expression levels of EZH2 and CXCL10 mRNA and protein in the two groups of cell lines and mouse tumor tissues were detected by reverse transcription polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), western blotting (WB), and immunohistochemistry. The chemotaxis and blocking experiments were used to validate the chemotaxis effect of CXCL10 on NK cells. The independent sample t-test was used to compare the groups. P<0.05 was considered statistically significant. Results: The HCC tumor-bearing mouse model experiment showed that HCC tumor growth was most remarkable in the NK clearance combined with the radiotherapy group compared to the radiotherapy group (P<0.05). Compared with the control group, the number of NK cells in the peripheral blood of nude mice in the radiotherapy group was significantly reduced, while the NK cell intratumoral infiltration was significantly increased (P<0.05). Flow cytometry and immunohistochemistry showed in vitro and in vivo expressional alterations. The average expression levels of EZH2 mRNA and protein in hepatocellular carcinoma cell lines and tumor tissues were decreased in the radiotherapy group than the control group and mouse tumor tissues (P<0.05), while the mRNA and protein expression levels of CXCL10 increased (P<0.05). The cell supernatant following radiotherapy enhanced NK cell chemotaxis but inhibited CXCL10 neutralization. EZH2 overexpression validated that radiotherapy up-regulated CXCL10 mRNA and down-regulated protein expression levels in in vitro and in vivo experiments (P<0.05). The chemotactic effect on NK cells was significantly weakened with EZH2 overexpression following radiotherapy. Conclusion: NK cells, as immune effector cells, are directly involved in radiotherapy- activated anti-HCC immunity. Importantly, radiotherapy inhibits EZH2 expression in hepatocellular carcinoma, thereby upregulating CXCL10 expression and enhancing intratumoral NK cell invasion.

Suppression of Inflammation-induced Abdominal Aortic Aneurysm Formation by Induction of Elastin Tolerance

Abdominal aortic aneurysm (AAA) is a vascular disease process whereby the aorta expands to apoint where rupture may occur. This serious condition is diagnosed in approximately 200,000 people in the United States per year and accounts for over 15,000 deaths annually. The only medical intervention proven to reduce the risk of AAA rupture is surgical repair; however, such repair is associated with high risk of death, reduced quality of life, and high expense. AAA is caused by the weakening of the artery wall due to inflammation-induced destruction of its structural components. Our clinical data shows increased levels of circulating elastin degradation products in patients with AAA, especially smokers, compared to risk factor matched controls. This observation led us to hypothesize that an immune reaction to elastin fragments initiates the inflammatory cascade in the aorta that leads to AAA formation. To test this hypothesis, C57BL/6 mice were injected with poly(lactide-co-glycolide) nanoparticle-encapsulated IL-10 to induce immune tolerance or nanoparticle-encapsulated control ovalbumin. Injection of elastin fragments was performed 7 days later to induce an immune response. AAA of the infrarenal aorta was induced by topical application of elastase during laparotomy procedure 14 days after nanoparticle injection. Aorta diameter was measured 16 days post-operatively with Microfil. Immunologic changes were evaluated by cytokine analysis, Tr1/Th17 cell ratio inperipheral blood, and splenic Th17 and Tr1 response to elastin. Based on prior work, we expect that induction of elastin tolerance using poly(lactide-co-glycolide) nanoparticle-encapsulated IL-10 will suppress abdominal aortic aneurysm expansion and promote an anti-inflammatoryenvironment characterized by increased Tr1/Th17 cell ratio, increased levels of anti-inflammatory cytokines, and decreased pro-inflammatory cytokine expression.

The impact of peripheral blood cell ratios in dogs with diffuse B-cellsmall lymphocytic lymphoma treated with CHOP protocol

In this study, pre-chemotherapy hematological values of 14 dogs diagnosed with diffuse B-cell small lymphocytic lymphoma were compared with the hematological data of 26 healthy dogs. Neutrophil/lymphocyte ratio (NLR), lymphocyte/monocyte ratio (LMR), platelet/lymphocyte ratio (PLR), and platelet/neutrophil ratio (PNR) were evaluated between two groups. Anemia and an increased total leukocyte count were observed in dogs with lymphoma compared to healthy ones. The PNR value was found to be significantly lower in dogs with lymphoma. It was concluded that more comprehensive studies are needed to clearly understand the diagnostic and prognostic importance of hematological parameters in B-cell small lymphocytic lymphoma of dogs.

Effect of acupuncture therapy on vaccine-induced immune response in d-galactose-induced aging rats

ObjectiveThis study aimed to explore whether acupuncture and moxibustion can enhance the immune response by increasing the expression of the endogenous adjuvant HSP70 mRNA. MethodForty Wistar rats were divided into four groups: model immune acupuncture group (A), model immune control group (B), normal immune acupuncture group (C), and normal immune control group (D). Model immune groups A and B were induced by injecting d-galactose for 6 weeks. Rats in groups A and C were then treated with low-frequency electroacupuncture (EA) at Zusanli (ST36), Guanyuan (CV4), and Baihui (GV20) and moxibustion for 3 weeks. Subsequently, all rats were observed for 2 more weeks. At the 12th week, diphtheria antitoxin titers were determined using the Vero cell trace neutralization method, CD4+T/CD8+T cell ratios in peripheral blood were examined by flow cytometry, and the relative expression of spleen cell HSP70 mRNA was measured by RT-PCR. ResultsCompared with the normal immune control, the diphtheria antitoxin titer, CD4+T/CD8+T cell ratio, and expression of spleen cell HSP70 mRNA significantly decreased in the model immune control group (P < 0.01). However, the model immune acupuncture group showed a significant increase in antitoxin titer (P < 0.01) and elevated CD4+T/CD8+T cell ratio and HSP70 mRNA expression (P < 0.05) after EA and moxibustion intervention. ConclusionAcupuncture and moxibustion may enhance the humoral immune response (diphtheria antitoxin titer) and cellular immune response (peripheral blood CD4+T/CD8+T cell ratio) by increasing the expression of the endogenous adjuvant HSP70 mRNA, suggesting that acupuncture may serve as a new vaccine adjuvant.

P06.19.A BEYOND T CELL TOXICITY - INTRATHECAL CXCL13 ELEVATION INDICATES B-CELL INVOLVEMENT IN NEUROLOGICAL IMMUNE-RELATED ADVERSE EVENTS FOLLOWING IMMUNE CHECKPOINT INHIBITION: 2 CASE OBSERVATIONS AND COMPREHENSIVE REVIEW

Abstract BACKGROUND Neurological immune-related adverse events (nirAE) can occur following cancer treatment with immune checkpoint inhibitors (ICI). Mainly attributed to autoreactive T-cells, nirAE usually respond to first line therapy with high-dose steroids (GC). Severe or fatal outcomes are rare &amp; most frequently reported in clinically overlapping syndromes with accumulating evidence of B cell autoimmunity. MATERIAL AND METHODS We present 2 patients who developed grade 3-4 nirAE with evidence suggestive for B cell involvement. RESULTS Case 1: A 75y female with metastatic melanoma developed double vision &amp; general weakness 2 weeks after the 1st cycle of ipilimumab &amp; nivolumab. Diagnostic workup showed pleocytosis (27 cells/µl) with elevated CXCL13 (316 pg/ml) in cerebrospinal fluid (CSF). Increases of creatine kinase, troponin T, elevated levels of anti-acetylcholine receptor antibodies &amp; positive anti-titin antibodies led to the diagnosis of myocarditis &amp; myositis/myasthenia gravis overlap syndrome. The patient received pulsed high-dose GC with tapering. CSF flow cytometry revealed intrathecal recruitment of CXCL13-responsive B cell helper T cells of a predominant inflammatory phenotype &amp; a highly increased pathological CD4/CD8 T cell ratio in peripheral blood. Clinically non-responding to GC, the patient received additional therapy with immunoglobulins (IVIG). 2 weeks later she was readmitted due to generalized myopathy with dropped head &amp; received a second cycle of high-dose GC since she refused plasmapheresis. Further escalation with rituximab could not be realized because the patient rapidly deteriorated &amp; deceased. Case 2: A 75y female with metastatic invasive enteric adenocarcinoma of the lung developed gait ataxia &amp; ataxia of the lower limbs 5 months after pembrolizumab therapy. CSF analysis showed a pleocytosis (248 cells/µl) with plasma cells, pronounced CXCL13 elevation (&amp;gt;488 pg/ml) &amp; positive screening for anti-neuronal cerebellar antibodies, suggesting ICI-mediated cerebellitis. The patient received high-dose GC &amp; IVIG for 5 days each, was discharged but readmitted 5 months later due to subacute onset of spastic paraparesis. Magnetic resonance imaging of the spine revealed thoracic myelopathy &amp; CSF showed mild pleocytosis (5 cells/µl), intrathecal immunoglobulin synthesis &amp; mild CXCL13 elevation (33 pg/ml). The patient completed a second cycle of steroids followed by rituximab targeting B-cell involvement &amp; currently 4 months later is clinically stable. CONCLUSION Intrathecal CXCL13 may serve as diagnostic tool of B cell involvement, here supported by intrathecal immunoglobulin synthesis, presence of plasma cells and/or severely altered immune cell compositions. Early treatment escalation with B cell depleting agents such as rituximab may help prevent fatal clinical courses.

Mean Platelet Volume-to-Lymphocyte Ratio Is a Biomarker of 1-Year Mortality in Patients With Diabetic Foot Infections.

We aimed to evaluate the value of 2 peripheral blood cell ratios, the mean platelet volume-to-lymphocyte ratio (MPVLR) and the neutrophil-to-lymphocyte ratio (NLR) as prognostic biomarkers of mortality in patients with diabetic foot infections (DFIs). We conducted a prospective observational study consisting of a cohort of 200 patients with moderate to severe DFIs consecutively recruited from our Diabetic Foot Unit, Hospital San Juan de Dios, San José de Costa Rica, Costa Rica from October 15, 2020, to December 15, 2021. We studied the variables associated with one-year all-cause mortality using a multivariate backward Cox's regression model. Nonparametric Spearman Rho was used to study the linear correlation between NLR and MPVLR and other inflammatory markers. The variables associated with all-cause mortality were retinopathy (hazard ratio [HR]: 2.55, 95% confidence interval [CI]: 1.22-5.33, P = .01), estimated glomerular filtration rate (HR: 0.979, 95% CI: 0.969-0.990, P < .001), HbA1c (HR: 0.825, 95% CI: 0.702-0.969, P = .01), and MPVLR (HR: 1.093, 95% CI: 1.020-1.172, P = .01). NLR showed a strong correlation with white blood cell count (r = 0.60 [<0.001]) and c-reactive protein (r = 0.63 [<0.001]), and a weak correlation with erythrocyte sedimentation rate (r = 0.33 [<0.001]), though it was not associated with mortality. In conclusion, apart from other risk factors of mortality, we have for the first time demonstrated that the increasing value of MPVLR is a factor associated with one-year mortality in patients with DFIs.

The Value of Peripheral Blood Cell Ratios in Primary Membranous Nephropathy: A Single Center Retrospective Study.

Primary membranous nephropathy (PMN) is a common cause of nephrotic syndrome in adults. Forty percent of the patients continue to progress and eventually develop into chronic renal failure. Although phospholipase A2 receptor (PLA2R) is the major antigen of PMN, the clinical features do not often parallel with the antibody titers. Therefore, it is significant to find relative credible markers to predict the treatment response. One hundred and eighteen PMN patients were recruited. The response to treatment was defined as ALB≥30g/L at 6 months and complete remission (CR) or not at the end of the follow-up. Renal outcome endpoint was defined as 50% or more Cr increase at the end. The patients with poor treatment effects had numerically higher platelet-lymphocytes ratio (PLR). For patients with CR or not, the difference was near to statistic significant (P=0.095). When analyzing CR or not, the fitting of the binary logistic regression model including both PLA2R Ab titer and PLR (Hosmer-Lemeshow test: χ 2=8.328, P = 0.402; OR (PLA2R Ab titer) = 1.002 (95% CI 1.000-1.004, P = 0.042); OR (PLR) = 1.006 (95% CI 0.999-1.013, P = 0.098)) was markedly better than that with only PLA2R Ab titer (Hosmer-Lemeshow test: χ 2=13.885, P = 0.016). The patients with renal function deterioration showed significantly higher monocyte-lymphocyte ratio (MLR) (0.26 (0.22-0.31) vs 0.18 (0.13-0.22), P = 0.012). PMN patients with poor treatment response tended to have higher PLR at the time of renal biopsy, and a higher MLR was associated with poor renal outcomes. Our findings suggested that PLR and MLR might be used to predict treatment efficacy and prognosis for PMN patients, respectively.

A Biomimetic Metal-Organic Framework Nanosystem Modulates Immunosuppressive Tumor Microenvironment Metabolism to Amplify Immunotherapy.

In the immunosuppressive tumor microenvironment (iTME), lactate secretion by cancer cells facilitates cell escape via M1 to M2 macrophage polarization, and T cell exhaustion. Therefore, lactate is a promising tumor immunotherapy target. In this study, we constructed a biomimetic nanosystem to modulate iTME metabolism to amplify immunogenic cell death (ICD)-induced immunotherapy. Metal-organic frameworks were coated with platelet membranes (PM) for tumor site-specific delivery and rationally designed to carry lactate oxidase (Lox) which catalytically consumed lactate, while oxaliplatin (Oxa) induced ICD. Due to PM-mediated targeting, the biomimetic nanosystem selectively accumulated in tumors and inhibited tumor growth. Encouragingly, due to effective iTME modulation, enhanced cytotoxic T cell infiltration in tumors was observed. Also, tumor-associated macrophage (TAM) phenotypes were polarized from M2 to M1 types, and regulatory T cell (Treg) levels decreased in vivo. Increased CD8+ T to CD4+ T cell ratios in peripheral blood and spleen were also observed. Thus, our biomimetic nanosystem effectively modulated the iTME and inhibited tumor growth by consuming lactate and amplifying ICD-induced immunotherapy. We provide new avenues into cancer immunotherapy, with a specific emphasis on iTME modulation, which lays the foundation for translational biomimetic nanosystems in clinical settings.

The clinical significance of peripheral blood cell ratios in patients with intracranial aneurysm.

Inflammation is an important factor in the development of aneurysm, and has been identified as a key characteristic predictive of rupture of intracranial aneurysm (IA). However, the role of inflammatory peripheral blood cell ratios in patients with IA has not been well delineated. A total of 1,209 patients, including 1,001 with unruptured IA and 208 with ruptured IA, were enrolled in this study. Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), platelet-to-neutrophil ratio (PNR), and platelet-to-white-blood-cell ratio (PWR) were compared between ruptured and unruptured IA. Compared with the ruptured IA group, the unruptured IA group had higher PNR {median, 65.96 [interquartile range (IQR) 48.95-85.05] vs. 37.78 (IQR, 23.17-54.05); p < 0.001} and PWR [median, 36.89 (IQR 29.38-44.56) vs. 22.39 (IQR, 16.72-29.29); p < 0.001]. In multivariate analysis, PNR and PWR were independently associated with ruptured IA (p = 0.001 and p < 0.001, respectively). Unruptured IA subgroup analyses according to the PHASES scores showed that a higher PHASES score was associated with significantly higher NLR and erythrocyte sedimentation rate (p < 0.001 and p = 0.025) and lower PNR and PWR (p < 0.001 and p = 0.007). We demonstrated that lower PNR and PWR levels are associated with ruptured IA and a higher PHASES score. Unlike many other inflammatory markers and bioassays, peripheral blood cell ratios are inexpensive and readily available biomarkers that may be useful for risk stratification in patients with cerebral aneurysm. However, a long-term prospective study is needed to clarify this matter.

Peripheral Blood Cell Ratios as Prognostic Indicators in a Neoadjuvant Chemotherapy-Treated Breast Cancer Cohort.

Breast cancer represents a heterogeneous condition in which the interaction between host immune response and primary oncogenic events can impact disease progression. Ratios of systemic blood-based immunocytes have emerged as clinically-relevant prognostic biomarkers in cancer patients. The NLR (neutrophil-to-lymphocyte ratio) has been shown to be prognostic in a variety of cancers, including breast cancer. However, evaluation of the prognostic value for overall survival (OS) and disease-free survival (DFS) of other key immunocyte ratios—neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), neutrophil-to-white cell count ratio (NWR), lymphocyte-to-white cell count ratio (LWR), monocyte-to-white cell count ratio (MWR), platelet-to-lymphocyte (PLR)—by breast cancer subtypes in a neoadjuvant chemotherapy (NAC) cohort remains to be fully explored. An NAC-treated breast cancer cohort, comprised of Luminal A, Luminal B, HER2-positive, and triple negative/basal breast cancers, treated at a tertiary referral center (minimum 3-year follow-up), was used to calculate immunocyte ratios and immunocyte cut-off values, calculated with >80% specificity (using decision tree modeling). The association with subtype-specific OS, DFS, and tumor grade was analyzed using cut offs calculated using both receiver operating characteristic curves and decision tree modelling. Decision tree calculated ratios showed that LMR (5.29) and MWR (0.06) were significantly associated with Luminal A OS (p = 0.004 and p = 0.022) and DFS (p = 0.004 and p = 0.022), and Luminal B OS (p = 0.027 and p = 0.008) and DFS (p = 0.005 and p = 0.007). NLR (1.79) and LWR (0.30) were significantly associated with HER2-positive OS (p = 0.013 and p = 0.043). NLR (1.79) and NWR (0.62) were significantly associated with DFS (p = 0.035 and p = 0.021). No significant association we observed between any immunocyte ratio in the triple negative cohort. Our results demonstrate the subtype-specific prognostic value of immunocyte ratios in NAC-treated breast cancer patients. Further validation of immunocyte ratios will provide clinicians with a new prognostic aid for disease management and monitoring.

Elevated serum IL-13 level is associated with increased Treg cells in tumor microenvironment and disease progression of diffuse large B-cell lymphoma.

Diffuse large B cell lymphoma (DLBCL) is the most common aggressive lymphoid malignancy, with an immunosuppressive microenvironment affecting clinical outcome. Interleukin (IL)-13 overexpression is observed in multiple solid tumors and contributes to tumor progression. This study aims to investigate pretreatment serum IL-13 levels and their relationship with the prognosis of DLBCL patients. One hundred and sixty-six patients with newly diagnosed DLBCL from June 2015 to July 2017 were included. Patients with elevated pretreatment serum IL-13 levels (IL-13≥1.63pg/ml) were classified into the high IL-13 group and they had significantly lower complete remission rate (60% vs. 74%, p=0.0059), higher progression rate (43% vs. 23%, p=0.0051), and poor progression-free survival (2-year PFS, 63% vs. 78%, p=0.0078) and overall survival (2-year OS, 75% vs. 92%, p=0.0027), when compared to those in the low IL-13 group (IL-13<1.63pg/ml). Meanwhile, increased Treg cell ratio in peripheral blood (p=0.0147) and elevated serum IL-2 levels (p=0.0272) were observed in the high IL-13 group. Moreover, RNA sequencing data showed that patients in the high IL-13 group had significantly elevated expression of chemokines and chemokine receptors (CCR4, CCL19, CCL21, CXCL2) related to Treg activation and recruitment. Consistent with the chemokine profile, tumor immunophenotyping analysis revealed that higher Treg cells recruitment in the high IL-13 group than the low IL-13 group (p=0.0116). In vitro, when lymphoma cells co-cultured with peripheral blood monocytes of healthy controls, metformin down-regulated both IL-13 level and Treg cell ratio, in consistent with the decreased serum IL-13 levels of patients after 6months of metformin maintenance therapy in the high IL-13 group. Taken together, pretreatment serum IL-13 level is related to the immunosuppressive microenvironment and poor clinical outcome of DLBCL patients and could be targeted by metformin, thus providing a new therapeutic strategy in treating DLBCL with high serum IL-13 levels.

Predictive and Prognostic Role of Peripheral Blood T-Cell Subsets in Triple-Negative Breast Cancer.

BackgroundTriple-negative breast cancer (TNBC), as a highly aggressive and metastatic tumor, can still not contain the medical needs. It has become an urgent problem to develop prognostic markers further and realize precision medicine. The predictive and prognostic significance of peripheral blood lymphocytes, as well as the clinicopathological factors affecting them, were explored in the present study.MethodsThe clinicopathological data of 278 patients with TNBC were collected and analyzed retrospectively. Peripheral blood lymphocytes (pBL) and blood routine indexes before treatment were quantified by flow cytometry analysis. Progression-free survival (PFS) and overall survival (OS) were analyzed by the Kaplan-Meier curve and Cox hazard proportion regression model. The associations between hematologic parameters and treatment response and clinicopathological characteristics were estimated by the Mann-Whitney test and Spearman test.ResultsCompared with all blood routine indexes, only a significant correlation between better treatment efficacy and higher peripheral CD4 +/CD8 + ratio of TNBC patients was observed (P=0.059), particularly those treated with chemotherapy combined with immune checkpoint inhibitors (P=0.048). Among the pBL subsets, CD4 + T lymphocyte was the only independent factor that could predict the prognosis of metastatic TNBC. Patients presenting higher values of peripheral CD4 + T lymphocytes showed longer PFS (median PFS 9 months vs. 5 months; HR =0.65, 95%CI: 0.440-0.973, P = 0.032) and OS (median OS 31 months vs. 16 months; HR=0 .63, 95%CI: 0.417-0.940, P< 0.01). Especially CD4+ was found predictive for prognosis in TNBC patients who received chemotherapy (P<0.05). Finally, the older age, higher clinical stage, and more advanced treatment lines were related to the lower level of CD4 +. The older age and having received neoadjuvant therapy were related to the lower CD4 +/CD8 + ratio (P<0.05).ConclusionThe baseline CD4+/CD8+ cell ratio in peripheral blood is associated with therapeutic response, especially for chemotherapy combined with immunotherapy. Peripheral CD4+ cells can steadily predict all clinical outcomes for patients with mTNBC, and this clinical prognosis prediction is significantly related to chemotherapy. Peripheral CD4+ and CD4+/CD8+ are both closely associated with clinicopathological parameters.

Peripheral Blood Cell Ratios as Prognostic Predictors of Mortality in Patients with Hepatitis B Virus-Related Decompensated Cirrhosis.

We sought to determine the correlations between peripheral blood cell ratios (neutrophil-to-lymphocyte ratio (NLR), mean platelet volume-to-lymphocyte ratio (MPVLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-neutrophil ratio (PNR), and platelet-to-white blood cell ratio (PWR)) and short-term prognosis in patients with hepatitis B virus (HBV)-associated decompensated cirrhosis (HBV-DeCi). A total of 144 HBV-DeCi patients were enrolled. Demographic characteristics and laboratory data for the patients were acquired from their medical records. Multivariate regression analysis was applied to determine risk factors for unfavorable outcomes. The predictive performance of different ratios was examined by receiver operating characteristic curve analysis. Liver function was assessed by the Model for End-Stage Liver Disease (MELD) score. Twenty-one HBV-DeCi patients (14.6%) had died at 30 days. Survival was associated with lower NLR, MLR, MPVLR, and MELD score and higher PWR and PNR than non-survival. Multivariate analyses identified NLR and MELD score as independent prognostic predictors. The ability of NLR to predict mortality was higher than that of MLR, PNR, MPVLR, and PWR, but slightly lower than that of MELD score. The present results suggest that peripheral blood cell ratios can be useful for predicting mortality in HBV-DeCi patients. These ratios should be considered together with other measures for evaluation of prognosis in HBV-DeCi patients and are conducive to clinical practice.

Peripheral blood cell ratios as prognostic factors in canine diffuse large B-cell lymphoma treated with CHOP protocol.

Diffuse large B-cell lymphoma (DLBCL) is the most common haematopoietic tumour in dogs and recognized as clinical model for its human counterpart. Recently, neutrophil-to-lymphocyte (NLR) and lymphocyte-to-monocyte (LMR) ratios have been shown to predict time-to-progression (TTP) and lymphoma-specific survival (LSS) in dogs with DLBCL treated with CHOP-based chemotherapy. We retrospectively evaluated in 59 dogs diagnosed with DLBCL the prognostic value of haematological parameters and derived ratios: NLR, LMR, platelet-to-lymphocyte (PLR) and platelet-to-neutrophil (PNR) ratios for TTP, LSS and associated secondary end-points (time-to-progression-rate [TTPR] and lymphoma-specific survival-rate [LSSR]) as rates at 180 and 365 days. PNR is an independent prognostic marker (p ≤ .001) for TTPR/180 and 365 days, dogs with a PNR above 0.032 were more likely to progress before 180 days (sensitivity 46.5%, specificity 87.5%, p=.004). On univariate analysis, NLR showed a prognostic significance for LSSR/180 (p=.006) and LSSR/365 (p=.009). A baseline NLR value below 7.45 was positively associated with survival at 180 days (sensitivity 52%, specificity 85.3%, p=.025). The presence of substage b, was associated with early progression and decreased survival at 180 days (p=.031). Anaemia significantly reduced LSSR at 365 days (p=.028). This is the first study evaluating PLR and PNR in canine DLBCL and demonstrates that PNR could be a predictor of early lymphoma progression. Since peripheral blood cell composition can be affected by several non-oncological causes, the development of larger multicenter studies with homogeneous inclusion criteria could help to better determine the true predictive values of blood cell ratios in dogs' DLBCL treated with CHOP chemotherapy.

The correlation between novel peripheral blood cell ratios and 90-day mortality in patients with acute ischemic stroke.

BackgroundWe aimed to investigate the correlation between the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), platelet-to-neutrophil ratio (PNR), platelet-to-white blood cell ratio (PWR) and 90-day mortality in patients with acute ischemic stroke (AIS).MethodsWe retrospectively included 633 patients with AIS from January 2017 to May 2018. The correlation between each indicator and the degree of neurologic deficit was assessed. Kaplan-Meier survival curves based on blood cell ratios were used to analyze the 90-day survival rate of patients with AIS.ResultsA total of 663 patients with AIS were enrolled, of which 24 (3.6%) experienced recurrence and 13 (2.0%) died. NLR>3.23 (odds ratio; OR = 2.236; 95% confidence interval [CI], 1.472–3.397; P<0.001), PNR<31.14 (OR = 0.471; 95% CI, 0.297–0.749; P = 0.001), and PWR<20.62 (OR = 0.498; 95% CI, 0.309–0.800; P = 0.004) were associated with an unfavorable 90-day prognosis. NLR>3.23, PWR<20.62, and PNR<31.14 were associated with an increased risk of 90-day mortality.ConclusionPNR, PWR, and NLR were associated with the 90-day mortality of patients with AIS. Patients with high NLRs or low PWRs and PNRs may have a greater risk of mortality than other patients. These clinical indicators may help clinicians judge unfavorable prognosis early and implement the appropriate interventions.

Differential approach to peripheral blood cell ratios in patients with systemic lupus erythematosus and various manifestations

New markers of systemic lupus erythematosus (SLE) activity are under investigation. In recent years, the researchers have been focusing increased attention on the role of haematological indicators in assessing the disease activity. Specifically, neutrophil-, basophil-, eosinophil-, monocyte- and platelet-to-lymphocyte ratios (NLR, BLR, ELR, MLR and PLR) have been considered. The specific objective of this study was to determine the suitability of the haematological markers for the assessment of SLE activity and SLE-related organ damage. This study is a retrospective analysis of 136 patients with SLE (124 women and 12 men) who received chloroquine/hydroxychloroquine (HQ/HCQ) monotherapy or HQ/HCQ therapy combined with low/medium doses of glucocorticoid. All patients were assessed for disease activity using the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) scale. In addition, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) inflammatory parameters were determined in each patient. NLR, BLR, ELR, MLR and PLR were evaluated and correlated with the SLE activity parameters and inflammatory markers. The mean values of the haematological indicators were compared in particular manifestations of SLE-induced organ damage. For numerical variables, descriptive statistics were calculated: median, standard deviation, minimum and maximum values. The Mann–Whitney U test was used for the comparison of continuous variables in the two groups. The Spearman rank correlation test was used to search for any relationships between variables. A p value < 0.05 was considered to be statistically significant. We have found a positive correlation between ELR, MLR and the SLEDAI scale (r = 0.22 and r = 0.27, respectively). NLR, MLR and PLR ratios were significantly correlated with ESR and CRP. Considerably higher NLR values were found in patients with cutaneous and/or mucosal symptoms and with kidney involvement compared to patients without such involvement (4.26 ± 4.2 vs 3.27 ± 2.7; p = 0.05 and 5.45 ± 5.6 vs 3.05 ± 2.0; p < 0.001 respectively). BLR and MLR were significantly higher in patients manifesting symptoms of vasculitis (0.09 ± 0.1 vs 0.02 ± 0.01; p < 0.001 and 3.1 ± 4.2 vs 0.3 ± 0.1; p < 0.001 respectively), arthritis and/or myositis (0.04 ± 0.09 vs 0.02 ± 0.01; p = 0.01 and 1.02 ± 2.6 vs 0.35 ± 0.4; p = 0.01 respectively), whereas elevated ELR ratios were observed in patients with vasculitis (0.4 ± 0.5 vs 0.08 ± 0.06; p < 0.001) compared to patients without such organ involvement. The PLR marker was substantially higher in patients exhibiting haematological disorders in the course of SLE (276.6 ± 226.4 vs 192.6 ± 133.5; p = 0.01). The results indicate that ELR and MLR are effective markers of SLE activity. The haematological indicators may predict SLE-dependent organ damage, particularly cutaneous, mucosal, arthritic, myositic, haematological and kidney involvement.

Long-term effects of omalizumab on peripheral blood cells and C-reactive protein levels in patients with chronic spontaneous urticaria.

Omalizumab's mechanism of action is not well-understood yet despite its strong therapeutic efficacy in chronic spontaneous urticaria (CSU). To determine the overall effect of omalizumab on peripheral blood cell counts and serum C-reactive protein levels (sCRP) during a 1-year follow-up in patients with CSU. Data of 74 patients (male/female: 20/54) were reviewed from medical charts. Leucocyte counts, percentages of peripheral blood cells(lymphocyte, monocyte, neutrophil [PPBN], eosinophil, basophil [PPBB]) and sCRP were recorded at baseline, 3rd, 6th, 12th months of omalizumab treatment. Although a dramatic increase in the mean PPBB (±SD) was observed at the 3rd month, PPBB (%) gradually decreased after the 3rd month (PPBB: 0.38 ± 0.21 [baseline] vs. 0.59 ± 0.3 [3rd month], p = .002). However, 12th month PPBB remained higher than baseline (PPBB:0.38 ± 0.21 [baseline] vs. 0.46 ± 0.27 [12th month], p = .03). A dramatic decrease in the mean PPBN (%) was noticed within the first 3 months (PPBN:62.85 ± 8.97 [baseline] vs. 58.37 ± 9.07 [3rd month], p = .04), and 12th month PPBN remained lower than baseline values (PPBN: 62.85 ± 8.97 [baseline] vs. 60.31 ± 8.02 [12th month], p = .045).Mean sCRP (mg/dL) decreased rapidly within the first 3 months (sCRP: 1.09 ± 1.53 [baseline] vs. 0.56 ± 0.45 [3rd month], p = .17) and 12th month sCRP still remained lower than baseline levels (sCRP: 1.09 ± 1.53 [baseline] vs. 0.83 ± 1.06 [12th month], p = .01). Omalizumab substantially increases PPBB,and reduces PPBN accompanied by a reduction in sCRP especially in the first 3 months; however, these effects may continue in the long-term. The alterations in peripheral blood cell ratios and sCRP may contribute to the therapeutic effect of omalizumab in CSU.

Role of Th17 Cells, Interleukin-17 and Matrix Metalloproteinase-13 in Pathogenesis of Henoch-Schonlein Purpura

To explore the immunopathogenesis of Henoch-Schonlein purpara (HSP) by detecting the levels of Th17 cells, IL-17 and matrix metallo proteinase-13 (MMP-13) in peripheral blood and the expression of IL-17 in skin lesions at acate phase of HSP. Th17 cell ratio in peripheral blood of HSP group and healthy control group was defected by flow cytometry, the plasma levels of IL-17 and MMP-13 in HSP group and healthy control group were defected by ELISA, and expression level of IL-17 in skin lesion of HSP group and skin tissue of healthy control group was deternined by: immunohistochemistry method. the ratio of Th17 cells in periphral blood of HSP group (1.21±0.59%) was very signif cantly higher than that in peripheral blood of control group (0.71±0.26%) ( t=4.907, P<0.01). The plasma levels of IL-17 and MMP-13 at acute phase of HSP were very significantly higher than those in control group (64.58±36.21) pg/ml vs (26.16±14.90) pg/ml and (17.57±5.40) pg/ml vs (11.53±4.40) pg/ml respectively (t=6.183, P<0.01 and t=5.022, P<0.01). The integrool optical density of IL-17 in skin lesin tissue of HSP group (7.26±2.34) was higher than that in control group (4.61±1.82) ( t=2.877, P<0.01). Th17 cells, IL-17 and MMP-13 may be involved in the immunological pathogenesis of HSP.

Increased Circulating Follicular Treg Cells Are Associated With Lower Levels of Autoantibodies in Patients With Rheumatoid Arthritis in Stable Remission.

To examine the expression and changes in function of circulating CD4+CXCR5+FoxP3+ follicular Treg (Tfr) cells in patients with active rheumatoid arthritis (RA) and in patients with RA in stable remission, and to clarify the role of Tfr cells in the pathogenesis of RA. Levels of Tfr cells and follicular helper T (Tfh) cells in the peripheral blood of 39 patients with active RA, 39 patients with RA in stable remission, and 33 healthy controls were detected by flow cytometry. The function of Tfr cells was measured by coculturing them with Tfh cells and B cells. Activated CD45RA-FoxP3high Tfr cells were also analyzed. Clinical indicators, including serum Ig and autoantibody levels, were tested, and correlations with Tfr cells were systematically analyzed. The Disease Activity Score in 28 joints (DAS28) was calculated, and correlation analysis with Tfr cells was conducted. The level of CD4+CXCR5+FoxP3+ Tfr cells and the Tfr cell:Tfh cell ratio in peripheral blood from patients with RA in stable remission were significantly increased compared with the same measures in patients with active RA and in healthy controls. The function of Tfr cells was enhanced, and the activated CD45RA-FoxP3high Tfr cell subset was increased in patients with RA in stable remission compared with healthy controls. Furthermore, the number of Tfr cells in RA patients was inversely correlated with IgG, rheumatoid factor, and anti-cyclic citrullinated peptide as well as with the DAS28. Circulating Tfr cells are increased as patients with RA achieve stable remission of disease, and increased Tfr cells can suppress autoimmunity in RA patients to stabilize their condition. Our results provide novel insight into RA pathogenesis.

Dynamic change in Th17/regulatory T cell ratio in peripheral blood of patients with acute hepatitis B and its significance

Objective: To investigate the dynamic changes in the frequencies of Th17 (CD3+CD8-IL-17+) and regulatory T cells (Treg, CD4+CD25+CD127low) and Th17/Treg ratio in the peripheral blood in patients with acute hepatitis B (AHB), as well as their association with the outcome of AHB. Methods: A total of 10 AHB patients were enrolled as observation group, and according to the outcome of AHB, these patients were further divided into acute stage group, early recovery group, and full recovery group. Another 10 healthy subjects who underwent physical examination were enrolled as control group. Flow cytometry was used to measure the frequencies of Th17 and Treg in peripheral blood, and the Th17/Treg ratio was calculated. An automatic biochemical analyzer was used to measure liver function parameters, and RT-PCR was used to measure HBV DNA. An one-way analysis of variance was used for comparison between groups, and the t-test was used for comparison between any two groups. Results: Compared with the control group, the acute stage group showed significant increases in the frequencies of Th17 and Treg (18.22%±4.13%/6.46%±2.46% vs 0.68%±0.29%/1.62%±0.18%,P< 0.01) and the Th17/Treg ratio (3.37±1.73 vs 0.42±0.20,P< 0.01). Compared with the acute stage group, the early recovery group showed a significant reduction in the frequency of Th17 (3.14%±1.90%,P< 0.01), a significant increase in the frequency of Treg (11.73%±1.76%,P< 0.01), and a significant reduction in the Th17/Treg ratio (0.27±0.19,P< 0.01). Compared with the early recovery group, the full recovery group showed a slight increase in the frequency of Th17 (3.31±0.95,P= 0.888), a significant reduction in the frequency of Treg (6.83%±1.85%,P< 0.01), but which was significantly higher than that in the control group (P< 0.01), and a slight increase in the Th17/Treg ratio (0.52±0.21,P< 0.05), which showed no significant difference between this group and the control group (P= 0.286). In the acute stage of AHB, HBsAg and HBeAg levels were positively correlated with Th17/Treg ratio (r= 0.639,P< 0.05;r= 0.633,P< 0.05). Conclusion: The dynamic changes in the frequencies of Th17 and Treg and the Th17/Treg ratio may be associated with the outcome of AHB.