Basophil Counts Research Articles

İlk Trimesterde Monosit Sayısı ve Monosit Bazlı Kan Hücre İndekslerinin Gebeliğin İntrahepatik Kolestazı Gelişimi, Şiddeti ve Prognozunu Öngörmedeki Rolü

Abstract
 Aim: To evaluate the effect of monocyte count and monocyte-based whole blood cell indices in the prediction of intrahepatic cholestasis of pregnancy (ICP) in the first trimester.
 Materials and Method: The clinical data of patients who presented to the Perinatology Clinic of the Turkish Ministry of Health ----xxxxxxx--- ICP between January 1, 2021, and October 1, 2022, were evaluated retrospectively. Maternal demographic parameters, gestational age at birth, fetal birth weight, first-trimester white blood cell, neutrophil, platelet, monocyte, lymphocyte, and basophil counts, lymphocyte-to-monocyte ratio (LMR), platelet-to-monocyte ratio (PMR), neutrophil-to-monocyte ratio (NMR), and basophil-to-monocyte ratio (BMR) were recorded. These parameters were compared between the ICP and control groups. The relationship between monocyte count, monocyte-based blood cell indices, and fasting bile acid levels was evaluated in the ICP group. The cut-off values of the first-trimester monocyte count and monocyte-based blood cell indices for the prediction of ICP were determined.
 Results: Gestational week at birth and fetal birth weight were significantly lower, and the neonatal intensive care requirement was significantly higher in the ICP group (p

The causal relationship between immune cells and different kidney diseases: A Mendelian randomization study.

Studies have suggested that the progress of most kidney diseases from occurrence to course and subsequent related complications are closely related to inflammatory reaction. Increased common leukocytes count in the family (neutrophils, eosinophils, basophils, lymphocytes, etc.) are also involved in the tissue damage of kidney diseases. However, these studies are only traditional observational studies, which cannot prove whether there is a causal relationship between these four kinds of leukocytes count and kidney diseases. We aim to explore the causal relationship between these four kinds of leukocytes count and kidney diseases by Mendelian randomization (MR). Large sample size of the genome-wide association database of four cell traits (neutrophil, basophil, lymphocyte, and eosinophil cell counts) in the leukocyte family were used as exposure variables. The outcome variables were various renal diseases (including chronic renal failure, acute renal failure, hypertensive heart or/and kidney disease, hypertensive renal disease, disorders resulting from impaired renal tubular function, and type 1 diabetes with renal complications). The covariates used in multivariable MR are also four cell traits related to blood cells (neutrophil, basophil, lymphocyte, and eosinophil cell counts). Instrumental variables and single nucleotide polymorphic loci were identified (P < 5 × 10-8. Linkage disequilibrium R2 < 0.001). The causal relationships were studied by inverse variance weighted (IVW), weighted median, and MR-Egger regression. Sensitivity analysis was also performed. In our study, IVW analysis results showed that increased neutrophil cell count was a risk factor for chronic renal failure (OR = 2.0245861, 95% CI = 1.1231207-3.649606, P = 0.01896524), increased basophil cell count was a risk factor for chronic renal failure (OR = 3.975935, 95% CI = 1.4871198-10.62998, P = 0.005942755). Basophil cell count was not a risk factor for acute renal failure (OR = 1.160434, 95% CI = 0.9455132-1.424207, P = 0.15448828). Increased basophil cell count was a protective factor for hypertensive heart and/or renal disease (OR = 0.7716065, 95% CI = 0.6484979-0.9180856, P = 0.003458707). Increased basophil cell count was a risk factor for disorders resulting from impaired renal tubular function (OR = 1.648131, 95% CI = 1.010116-2.689133, P = 0.04546835). Increased lymphocyte cell count was a risk factor for hypertensive renal disease (OR = 1.372961, 95% CI = 1.0189772-1.849915, P = 0.03719874). Increased eosinophil cell count was a risk factor for type 1 diabetes with renal complications (OR = 1.516454, 95% CI = 1.1826453-1.944482, P = 0.001028964). Macrophage inflammatory protein 1b levels was a protective factor for renal failure (OR = 0.9381862, 95% CI = 0.8860402-0.9934013, P = 0.02874872). After multivariable MR was used to correct covariates (neutrophil, basophil, and lymphocyte cell counts), the correlation effect between increased eosinophil cell counts and type 1 diabetes with renal complications was still statistically significant (P = 0.02201152). After adjusting covariates (neutrophil, basophil, and eosinophil cell counts) with multivariable MR, the correlation effect between increased lymphocyte cell counts and hypertensive renal disease was still statistically significant (P = 0.02050226). This study shows that increased basophils can increase the relative risk of chronic renal failure and renal tubular dysfunction, and reduce the risk of hypertensive heart disease and/or hypertensive nephropathy, while increased basophil cell count will not increase the relative risk of acute renal failure, increased neutrophil cell count can increase the risk of chronic renal failure, increased lymphocyte cell count can increase the relative risk of hypertensive nephropathy, and increased eosinophil cell count can increase the relative risk of type 1 diabetes with renal complications. Macrophage inflammatory protein 1b levels was a protective factor for renal failure.

Full Blood Count Parameters in COVID-19 Patients With Disease Severity, Patient Outcome and Vaccination Status

Introduction: A link between full blood count (FBC) parameters with the severity and prognosis of individuals with coronavirus disease 2019 (COVID-19) infection is shown. We aim to identify changes in FBC parameters depending on patients’ characteristics, the severity of the disease and vaccination status. Methods: A cross-sectional retrospective laboratory study is done on 208 respondents who were selected from February 2021 to December 2022 in the Pathology Department of the Tuanku Ja’afar Hospital in Negeri Sembilan. All patients are confirmed COVID-19 positive by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) of pharyngeal and nasal swab specimens. Patients are further classified based on their COVID clinical stages, severity, vaccination status and outcome. The statistical data are analysed using IBM SPSS version 27. Results: Severe patients have significantly lower absolute lymphocyte count (ALC), absolute monocyte count (AMC), absolute eosinophil count (AEC) and absolute basophil count (ABC) but higher mean platelet volume (MPV), absolute neutrophil count (ANC), neutrophil to lymphocyte ratio (NLR) and immature granulocytes (IG) compared to non-severe patients (p &lt; 0.05). Similar findings are seen among non-survivors (p &lt; 0.05). Fully vaccinated patients have significantly lower NLR and MPV but higher ALC, AMC, AEC and ABC than unvaccinated or partially vaccinated patients (p &lt; 0.05). Conclusion: Selected FBC parameters of COVID-19 patients (platelets, ANC, NLR, MPV, ALC, AMC, AEC, and ABC) are significantly different depending on patients’ severity, outcome and vaccination status. These results might give a clear insight for clinicians to anticipate the severity and outcome of patients based on the patient’s FBC parameters.

Characterization of SARS-CoV-2-specific humoral immunity and associated factors in the healthy population post-vaccination

ObjectivesTo investigate factors that may influence humoral immunity post-vaccination with a COVID-19-inactivated vaccine (SC2IV). MethodsA total of 1596 healthy individuals from the Seventh Affiliated Hospital, Sun Yat-sen University (1217) and Shenzhen Baotian Hospital (379) were enrolled in this study among which 694 and 218 participants were vaccinated with two-dose SC2IV, respectively. Physical examination indices were recorded. The levels of neutralizing antibody (NA), Spike IgG, receptor-binding domain (RBD) IgG, RBD IgG + IgM + IgA, and nucleocapsid IgG of SARS-CoV-2 were measured by a non-virus ELISA kit. Multiple statistical analyses were carried out to identify factors that influence humoral immunity post-vaccination. ResultsThe two-dosage vaccination could induce NA in more than 90 % of recipients. The NA has the strongest correlation with anti-RBD IgG. Age is the most important independent index that affects the NA level, while basophil count, creatine kinase-MB, mean corpuscular hemoglobin, the ratio of albumin to urine creatinine, and thyroglobulin antibody have relatively minor contributions. Indices that affect the NA level were different between males and females. Antibodies targeting other epitopes of SARS-CoV-2 were detected in recipients without anti-RBD. ConclusionsThe factors identified in association with the NA level post-vaccination may help to evaluate the protective effect, risk of re-infection, the severity of symptoms, and prognosis for vaccine recipients in clinical.

Role of inflammation in determining the severity of COVID-19 infection in patients with diabetes: A comparative study.

There is a need to consider the geographical origins when studying the association between COVID-19 and the comorbid conditions. To examine the role of inflammation in determining the severity of COVID-19 among hospitalized patients with diabetes and compare these roles with those who does not have diabetes. A cross sectional comparative design was used with a convenience sample of 352 patients. Samples were collected from hospitalized patients with COVID-19 who were divided into 2 groups (diabetes and non-diabetes). Data regarding results of selected inflammatory markers and sociodemographic were collected. The severity of COVID-19 differed significantly between the diabetes and non-diabetes groups (Chi square = 25.58 P < .05). There was significant difference in the mean scores of neutrophil counts, monocyte count, Basophil count, erythrocyte sedimentation rate, partial thromboplastin time, C-creative protein, platelets, white blood cells, and mean cellular hemoglobin center between those with and those without diabetes. The diabetes were shown more increased in the predictors and severity of the COVID-19 disease. However, neutrophil to lymphocyte ratio, neutrophil count, and age were the significant predictors of the severity level of COVID-19 among patients with diabetes. In conclusion, our study addressed the influence of having diabetes among hospitalized patients with moderate and severe COVID-19 infection. The results showed that severity of COVID-19 infection was affected by diabetes where those with diabetes had more tendency to suffer from the severe form of the disease rather that the moderate level.

User verification of Abbott Alinity HQ hematology analyzer

Abstract Objectives This study aims to evaluate the performance characteristics of the Alinity HQ hematology analyzer in a routine laboratory setting. Methods In the study, precision (short-term and long-term precision), accuracy (method comparison with Abbott Cell Dyn Ruby and estimation of bias), confirmation of a background (Limit of Blank, LoB), and carry-over were used to evaluate the performance of Alinity HQ as recommended by ICSH, CLSI guidelines EP15-A3, EP09, EP17A2, and H26-A2. Acceptance criteria were based on manufacturer technical specifications and the EFLM Biological Variation Database. Results According to the short-term precision results, except for mean corpuscular volume (MCV) and mean corpuscular hemoglobin concentration (MCHC), all measurements exhibited coefficient variations (CV) lower than their verification limits. Basophil, eosinophil, and monocyte counts, as well as mean corpuscular hemoglobin (MCH), MCHC, and red cell distribution width standard deviation (RDW-SD), did not meet the allowable imprecision criteria for the long-term precision study. The estimated bias for all analytes was within verification limits. However, the method comparison study showed concentration-dependent variations for MCHC, MCH, and mean platelet volume (MPV) parameters. Furthermore, the correlation of parameters between Alinity HQ and Cell Dyn Ruby ranged from 0.46 to 1.00. The LoB and carry-over studies demonstrated satisfactory performance for the Alinity HQ analyzer. Conclusions Although some parameters had higher CVs than expected and concentration-dependent bias, the overall analytical performance of Alinity HQ was found to be satisfactory. Alinity HQ is an accurate, highly precise analyzer with good analytical performance, suitable for high-volume laboratories.

#211 : The Causal Effects of Circulating Biomarkers of Immunity and Inflammation on Endometriosis: A Bidirectional Mendelian Randomization Analysis

Background and Aims: Endometriosis is a chronic gynecological disease with a high prevalence among reproductive-aged women. Several studies have investigated the causal effect of different serum biomarkers of immunity and inflammation on the occurrence and progression of endometriosis. However, the results of these studies remained inconclusive and even controversial. Herein, this study aims to analyze the causal associations of genetically predicted levels of different circulating biomarkers of immunity and inflammation with the risk of endometriosis using a bidirectional two-sample Mendelian randomization (MR) approach. Methods: The single-nucleotide polymorphisms (SNPs) of exposures which indicate the genetic variants were used as instrumental variables (IVs) and were all obtained from the genome-wide association study (GWAS) of European ancestry from the IEU GWAS database. Besides, we performed bidirectional MR analysis to test the associations. The causal effects were estimated through the inverse-variance weighted method (IVW). The sensitivity examinations of each result after the MR analysis were performed to detect if any heterogeneity and pleiotropy existed. Results: Our results demonstrated that higher interleukin-9 (IL-9) level was associated with the occurrence of endometriosis, while macrophage colony stimulating factor (MCSF) level, TNF-related apoptosis inducing ligand (TRAIL), sE-Selectin and basophil count showed the opposite. Genetically predicted endometriosis was related to higher immunoglobulin E (IgE) level and platelet count. No evidence of bidirectional association was detected on the other serum inflammatory biomarkers with endometriosis. Neither pleiotropy nor heterogeneity was found in our study. Conclusion: Our results suggested that some dysregulated circulating biomarkers of immunity and inflammation is causally associated with the occurrence of endometriosis, and at the same time endometriosis may lead to the abnormality of some of these factors. Our findings provided genetic insights on potential novel strategies in the primary prevention, diagnosis and treatment of endometriosis.

Unbalanced Aryl Hydrocarbon Receptor Expression in Peripheral and Lesional T Cell Subsets of Atopic Dermatitis.

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor, which is involved in the pathogenesis of a variety of skin diseases such as atopic dermatitis (AD). In this study, we aimed to study the AhR-expressing cells in T helper 17 (Th17), T helper 22 (Th22), regulatory T cells (Treg) and B cells in peripheral blood and in AD skin lesions. Twenty AD patients defined according to the Chinese criteria of atopic dermatitis and eighteen healthy subjects were included in our study. The AhR-expressing Th17, Th22, Treg and total B cells in peripheral blood were measured by flow cytometry. The AhR+ Th17 cells and AhR+ Th22 cells in AD skin lesions were measured by immunofluorescence. The mRNA of AhR, interleukin (IL)-22, IL-17A, IL-10, Foxp3, RORγT and TGF-β in peripheral blood mononuclear cells (PBMCs) was measured by real-time quantitative polymerase chain reaction. The expression of AhR in peripheral CD4+ T cells, Th22 cells, Treg cells and total B cells was significantly increased in AD. AhR+IL-17A+ and AhR+IL-22+ lymphocytes were also increased in AD skin lesions. The mRNA levels of AhR, IL-22 and IL-17A in PBMCs in AD patients were significantly higher. AhR mRNA levels in PBMCs positively correlated with peripheral basophil count, peripheral eosinophil count and mRNA levels of IL-22. AhR was highly expressed in subpopulations of CD4+ T cells in peripheral blood and skin lesions of AD, suggesting that AhR might contribute to the pathogenesis of AD.

Title: Machine Learning Models for Basophil Enumeration and Its Potential Application for Chronic Myeloid Leukemias in Flow Cytometric Analysis

Background: In marrow, basophil counts are low but may increase in reactive or neoplastic conditions including chronic myeloid leukemia (CML). The current basophil enumeration by the gating approach is operator dependent with variable accuracy. Objective: To enumerate basophils and to compare basophil and granulocyte counts between potential CML cases (pCMLs) and controls using machine learning (ML) models. Research Methods: pCMLs and controls (117 and 883 marrow samples, respectively) were selected using key-word search from flow-cytometry (FC) reports. In general, pCMLs had both granulocytosis and basophilia pending tests for t(9;22). The datasets were from an antibody panel - FS_SS_HLA-DR_CD33_CD34_CD117_CD45. Three preliminary models, the basophil enumeration model (BEM), granulocyte enumeration model (GEM), and granulocyte-basophil model (GBM) were used (data not published). GBM incorporates basophil and granulocyte counts from BEM and GEM, and separates the cases into two groups, GB-1 with high granulocyte and basophil counts and GB-2 with low basophil and/or granulocyte counts. Results: BEM revealed higher basophil counts in pCMLs than those in the controls (median: 734 vs. 54). However, 35 (5%) of the controls had &amp;gt;390 basophils (≥25 percentile in pCMLs) (Figure-1). GBM classified 96 (90%) pCMLs as GB-1 and 11 as GB-2. Conversely, GBM classified 74 (10%) controls as GB-1 and the remaining 672 as GB-2 (Figure-2). Multiple scatter plots in figure 1-a illustrate two-dimensional distributions of a basophil cluster in a pCML case (green: CD117-positive basophils [often increased in pCML]; red: CD117-negative basophils). Conclusion: In experimental setting, BEM is an efficient high-throughput alternative for basophil enumeration with high consistency and is opterator-independent. GBM could separate pCMLs from most controls automatically. Future ML models will use confirmed CML-cases and additional antibody markers in a multicolor FC platform.

Machine Learning for Identification of High-Risk Clonal Haematopoiesis Using Blood Count Data

Introduction: Clonal haematopoiesis (CH) is a common, age-related phenomenon associated with an increased risk of myeloid malignancies (MM), raising the prospect of screening to identify individuals at high risk of progression from CH to MM. The nature of the driver mutation(s) is the major determinant of the risk of progression to MM. Presently, the identification of these mutations relies on next generation sequencing (NGS) of blood DNA, making it impractical to identify those at risk at scale. We previously reported that the presence of CH is associated with changes in complete blood count (CBC) parameters such as the red cell distribution width (RDW), mean corpuscular volume (MCV) and others. However, individual parameters have limited discriminative power to distinguish those with CH versus those without. Here, we present a machine learning (ML) pipeline applied to a combined CBC dataset, which can be harnessed to improve our ability to identify individuals with high likelihood of carrying CH, who can subsequently be prioritised for genetic testing. Methods: Whole exome sequencing (WES) data from 454,052 UK Biobank (UKB) participants were analysed using Mutect2 to detect CH-driver mutations across the exons of 43 CH-associated genes. Germline variants were filtered using a panel of ormal and a one-sided exact binomial test. A final set of driver mutations was derived by filtering variants based on a pre-defined list of recurrent CH mutations or recurrence of &amp;gt;= 7 times in haematological cancers in the catalogue of somatic mutations in cancer. Fields pertaining to blood count variables were extracted and filtered to remove individuals with missing data, extreme outliers, highly correlated parameters and variables with near zero-variance resulting in 434,057 participants with complete datasets. Individuals were annotated as “CH” or “no-CH”; a Random Forest (RF) binary classifier was optimised on age, sex and 13 blood count variables as features. To quantify the robustness and stability of the model, the RF optimisation was iterated ten times, on a customised cross validation approach by using a different random sample from the majority (control) class each time. All ML models were constructed using the Caret package (R version 3.6.3). Results: We first found that RF classifiers to identify the presence of CH overall performed poorly (median AUC: 0.640/0.671 for any/large clone VAF &amp;gt;=10% CH respectively). However, gene-specific models showed that the presence of CH associated with mutations in certain high risk genes ( SF3B1, SRSF2, JAK2, CALR) could be predicted from blood counts more confidently (median AUC 0.776, 0.834, 0.933, 0.849 respectively). By contrast, mutations in the more common CH driver genes ( DNMT3A and TET2) could not be accurately predicted from blood count data (median AUC 0.618 and 0.666 respectively) (Figure 1). In light of these findings, we proceeded to build a single RF model to predict the presence of high-risk CH associated with mutations in any of SF3B1, SRSF2, JAK2 or CALR. This performed well, with median AUC of 0.816/0.888 for any/large clone high-risk CH respectively (Figure 2). Our RF models were also able to give insights into novel blood count association with specific types of CH; in particular we found that the basophil count was an important predictor of the presence of CH driven by mutation in codon K57 of the GNB1 gene. To investigate this further, we analysed basophil counts in the UKB and confirmed that basophilia (basophils &amp;gt;0.2 x 10 9/L) was more common amongst carriers of GNB1-K57 mutations (14/234 = 5.9%) than controls (2597/433,863 = 0.5%). Conclusions: Data-driven ML models applied to blood count data can identify individuals with high-risk CH driven by genes associated with progression to myelodysplastic syndrome and myeloproliferative neoplasms, who should be prioritised for genetic testing for somatic mutations. The future integration of raw blood analyser and longitudinal blood count data into predictive models would be an important next step towards improving our ability to identify individuals that may harbour CH and help facilitate the introduction of large-scale screening for the phenomenon.

Genetic evidence for causal effects of leukocyte counts on risk for rheumatoid arthritis

Rheumatoid arthritis (RA) is an autoimmune disease characterized by the accumulation of leukocytes and inflammatory mediators within the synovial tissue. Leukocyte counts are proposed to play a role in the pathogenesis of RA. However, the causality remains unclear. To investigate the causal relationship between various leukocytes and RA by implementing two-sample univariable Mendelian Randomization (MR) and multivariable MR. MR analysis was performed using respective genome-wide association study (GWAS) summary statistics for the exposure traits (eosinophil counts, neutrophil counts, lymphocyte counts, monocyte counts, basophil counts, and white blood cell counts) and outcome trait (RA). Summary statistics for leukocytes were extracted from the Blood Cell Consortium meta-analysis and INTERVAL studies. Public GWAS information for RA included 14,361 cases and 43,923 controls. Inverse variance weighted, weighted median, MR-Egger regression, MR pleiotropy residual sum and outlier, and multivariable MR analyses were performed in MR analysis. Univariable MR found elevated eosinophil counts (OR 1.580, 95% CI 1.389–2.681, p = 1.30 × 10–7) significantly increased the risk of RA. Multivariable MR further confirmed that eosinophil counts were a risk factor for RA. Increased eosinophils were associated with higher risk of RA. Further elucidations of the causality and mechanisms underlying are likely to identify feasible interventions to promote RA prevention.

Effects of Dietary Mannan Oligosaccharides on Growth, Nonspecific Immunity and Tolerance to Salinity Stress and Streptococcus iniae Challenge in Golden Pompano, Trachinotus ovatus

The effects of dietary supplementation with mannan oligosaccharide (MOS) on growth performance, haematological parameters, abundance of intestinal Vibrio spp., immune response, and tolerance to low salinity stress and Streptococcus iniae challenge were evaluated in pompano (Trachinotus ovatus). Pompano (3.24 ± 0.45 g) were fed six diets including a basal diet as control, and the basal diets supplemented with 0.1%, 0.2%, 0.4%, 0.6%, or 0.8% MOSs for 8 weeks. The results showed that pompano fed 0.1%–0.4% MOS had significantly improved specific growth rates ( P ≤ 0.039 ). Dietary MOS did not affect the survival rate of pompano ( P = 0.192 ). WBC count was significantly higher in fish fed diets containing 0.1%–0.6% MOS. Dietary MOS increased lymphocytes count ( P ≤ 0.042 ) and reduced monocytes and basophils counts ( P ≤ 0.019 ); however, no effects were found on neutrophils and eosinophil numbers ( P ≥ 0.064 ). Intestinal Vibrio spp. counts reduced in fish fed diets containing 0.1%–0.4% MOS ( P ≤ 0.035 ). The phagocytic ratio significantly increased in pompano fed diets containing 0.1%–0.6% MOS ( P ≤ 0.015 ), while the phagocytic index and serum lysozyme activity in fish fed 0.1%–0.4% MOS were significantly higher than the control ( P ≤ 0.035 ). There were significant positive correlations between MOS levels and fish growth on days 14, 28, 42, and 56 ( P ≤ 0.049 ). In addition, dietary MOS levels were highly correlated with blood parameters, abundance of intestinal Vibrio spp., and immune responses. Optimal dietary MOS requirements for maximal growth were estimated to be 0.440% on day 21 (R2 = 0.861), 0.385% on day 28 (R2 = 0.877), 0.371% on day 42 (R2 = 0.891), and 0.365% on day 56 (R2 = 0.750), showing decreasing tendency in MOS requirement as fish size increased. Furthermore, the optimal MOS concentration for maximal immunity based on lysozyme activity was estimated to be 0.431% (R2 = 0.817) on day 56. In addition, fish fed 0.1%–0.4% MOS showed better resistance to low salinity stress and Streptococcus iniae challenges ( P ≤ 0.014 ). In conclusion, MOS supplementation effectively reduced the prevalence of intestinal Vibrio spp. and enhanced the growth, immune responses, and tolerance to low salinity stress and Streptococcus iniae in juvenile pompano.

Transfluthrin is Associated with High Susceptibility to Asthma in Children with Promoter Variants ofBeta Chain of High-Affinity Receptor IgE and Tumour Necrosis Factors-α Genes.

This study investigates the genetic variations in FcεR1β-109 C/T (rs512555) and TNF-α-308 G/A (rs1800629) genes and examines whether the mosquito repellent transfluthrin (TFT) modifies the risk for asthmatic children. A case-control study was conducted involving 130 asthmatic children and 123 age-sexmatched controls. Differential leukocyte counts, IgE, and hs-CRP levels were estimated using a five-part haematology analyzer and Beckman Coulter (AU480), respectively. Genetic variations in FcεR1β-109 and TNF-α-308 were analysed using restriction fragment length polymorphism. Serum TFT levels were measured using gas chromatography-tandem mass spectrometry. Asthmatic children had significantly increased total leukocyte,neutrophil, lymphocyte, eosinophil, and basophil counts (p < 0.0001), while their monocyte counts were lower compared to controls (p < 0.0001). TFT levels were higher in asthmatic children (1.38 ± 0.91 vs. control 0.69 ± 0.41µg/L, p < 0.0001), which predominantly induced wheezing. Elevated TFT levels were associated with an increased risk of childhood asthma (OR: 3.08, p < 0.0001). Children with the FcεRIβ TT (OR: 2.39, p < 0.017) and TNF-α GG genotypes (OR: 7.17, p < 0.0001) were more susceptible to asthma. TFT synergistically enhanced the risk of asthma in both FcεRIβ-109 TT (OR: 5.3, p = 0.001) and TNF-α-308 GG (OR: 17.18, p < 0.0001) genotypes. TFT levels were correlated with IgE (r = 0.363; p = 0.006), hs-CRP (r = 0.324; p = 0.049) and eosinophil (r = 0.300; p = 0.038), respectively. IgE and eosinophils were correlated (r = 0.599, p = 0.001) in the FcεRIβ TT genotype-carrying asthmatic children. Similarly, neutrophils and hs-CRP were correlated (r = 0.768, p < 0.0001) in asthmatic children with TNF-α GG genotype. The risk of asthma is inherently higher in children with FcεRIβ TT and TNF-α GG variants. TFT exposure amplifies the risk of asthma in children among all the subgenotypes of both genes. TFT influences IgE and eosinophil in FcεRIβ TT genotype while it influences neutrophils and hs-CRP in TNF-α GG genotypes.

BIOM-42. LONGITUDINAL IMMUNE PROFILES OF LOWER GRADE ADULT GLIOMA PATIENTS

Abstract Immune dysregulation is a known characteristic of glioma, however there is little known about the peripheral immune status of lower-grade (LrGG) glioma patients across the course of disease. Using immunomethylomic (deconvoluted blood DNA methylation) data from the UCSF Immune Profiles Study, we explore changes in patient peripheral blood immune cell profiles in newly diagnosed and recurrent LrGG patients. For patients receiving radiation (RT) and temozolomide (TMZ) (n = 75), blood is collected pre-RT/TMZ, post-RT/TMZ, before, during, and after adjuvant TMZ (if applicable). For patients followed only by MRI (n = 53) and those with other treatment plans (n = 67), blood is collected at MRIs, and if applicable, before radiation. For all patients, blood is also collected before new treatment intervention. For patients (LrGG IDH mutated) with paired pre- and post-surgery samples (n = 139), we observed a significant post-surgery increase in the count of memory B-cells (p = 1.7e-5), neutrophils (p = 0.0001), basophils (p = 8.7e-5), monocytes (p = 0.0001), and T-regulatory cells (p = 0.0001) along with a significant decrease in natural killer cells (p = 0.0003). Treatment was also associated with altered patient immune profiles. The use of dexamethasone was associated with an increased count of B-memory (p = 0.0001) and B-naïve cells (p = 0.0001), monocytes (p = 2.1e-5), and neutrophils (p = 3.7e-6) post-surgery. Patients receiving chemoradiation (n = 12) exhibited significant and temporally sustained decreases in B-memory (p &amp;lt; 0.0001), B-naïve (p = 0.005), CD4 naïve cells (p = 0.002), and in neutrophils (p = 0.001). Patient follow-up, data collection, and further analyses are ongoing. These results shed light on the dynamic and variable immune changes in LrGG patients and provide a guide for future prognostic and therapeutic studies.

Potential blood markers as screening tools for subjects with low back pain: an age- and gender-matched cross-sectional analysis

Background Mechanical and inflammatory factors were suggested as the causes of spine degeneration and low back pain (LBP). Previous studies partly reported the association of LBP with inflammation. However, none of them compared patients with LBP and asymptomatic subjects in terms of complete blood count and inflammatory markers in detail. We aimed to analyze the association of serum white blood cell (WBC) count, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) with chronic LBP by comparing the patients with chronic LBP and age- and gender-matched asymptomatic subjects. Methods Lumbar intervertebral disc degeneration and vertebral end-plates were evaluated using Pfirrmann grading and Modic classification on lumbar spine magnetic resonance images, respectively. Serum WBC counts, CRP levels, and ESRs were recorded from chart reviews. Results We included 147 patients with chronic LBP and 101 asymptomatic subjects. Patients with chronic LBP had significantly higher serum neutrophil, monocyte, and basophil counts, higher neutrophil-to-lymphocyte ratio, higher ESR, and lower serum CRP levels compared to the asymptomatic subjects. Serum monocyte and basophil cell counts and ESR were the most remarkable predictive factors for chronic LBP, severe IVDD, and Modic changes. Higher serum monocyte and basophil cell counts and higher serum ESR above cut-off values of 0.42 × 103/μL, 0.025 × 103/μL, and 3.5 mm/hour could be used as screening tools for subjects with persistent LBP in primary care. Discussion Higher serum monocyte and basophil counts and serum ESR above new cut-off values should highlight the need to obtain early spinal imaging to prevent chronicity in patients with LBP.

Abstract 19053: Peripheral Eosinophil Count is Associated With Left Ventricular Systolic Dysfunction During Spontaneous Coronary Artery Dissection

Background: Spontaneous coronary artery dissection (SCAD) is an underdiagnosed condition disproportionally affecting young women, particularly during the peripartum period and/or in the presence of systemic inflammatory and autoimmune diseases. Tissue-level studies have demonstrated inflammatory infiltrates with adventitial or peri-adventitial eosinophilia at the site of SCAD lesions. Less is known regarding how systemic markers of immune activation associate with cardiac dysfunction in SCAD. Hypotheses: Higher eosinophil count and Neutrophil-to-Lymphocyte Ratio (NLR) associate with LV systolic dysfunction in SCAD patients. Methods: In individuals diagnosed with SCAD who underwent CBC with differential and echocardiography within the same presenting hospital encounter, we performed age- and sex-adjusted logistic regressions with eosinophil count (% of differential) and NLR (% of differential) as primary exposures and LVEF&lt;55% as the dichotomous endpoint. A p&lt;0.05 was considered statistically significant. We explored associations of neutrophil, lymphocyte, monocyte, and basophil counts with LVEF in secondary analyses. Results: In SCAD patients with complete CBC and LVEF data (N=36; mean age 49.9 years at diagnosis, 28 female), peripheral eosinophil count was associated with significantly higher odds of systolic dysfunction [OR of LVEF&lt;55% per every 1% higher eosinophil count = 1.87; 95% CI 1.04, 3.36; p=0.04]. NLR ratio was not associated with LV systolic dysfunction (OR 1.05; 95% CI 0.94, 1.18; p=0.35) nor were other circulating leukocyte fractions. Conclusion: Peripheral eosinophil count, but not other circulating leukocyte counts, was associated with LV systolic dysfunction as measured by LVEF &lt;55%. These findings provide complementary support to pathology-based evidence of eosinophilia observed in SCAD lesions and require confirmation in future longitudinal studies of changes in LV function following SCAD events.

IMPACT OF BLOOD PARAMETERS ON BCR/ABL1 P210 TESTING IN PATIENTS WITH CHRONIC MYELOID LEUKEMIA IN TURKIYE

Objective: Chronic myeloid leukemia (CML) is one of the most common hematological malignancies derived from the BCR/ABL1 fusion gene. Patients with CML generally manifest leukocytosis with basophilia and neutrophilia. The verification of CML is often based on the detection of BCR/ABL1 fusion. We aimed to investigate the impact of peripheral blood (PB) differential and complete blood count (CBC) on BCR/ABL1 p210 test ordering in patients with suspected CML. &#x0D; Methods: We performed a retrospective assessment of patients tested for the first time for BCR/ABL1 p210 fusion. We obtained clinical and laboratory findings of 235 patients from the database of our clinic. BCR/ABL1 p210 fusion was detected by quantitative real-time polymerase chain reaction (RT-qPCR). We implemented t-tests or Mann–Whitney U tests for the comparison of continuous data. We plotted the receiver operating characteristic (ROC curves) and calculated the area under the ROC curve (AUC) for each parameter. &#x0D; Results: Among 235 patients, 25 (%10.6) received a new diagnosis of CML. CML patients had significantly increased white blood cell count (WBC) with differential. Absolute basophil count showed the highest area under the ROC curve (AUC) value of 0.829, which had a cut-off value of 0.3 × 103/ µL. 76.00% of CML cases had an absolute basophil count of ≥0.3 × 103/µL, while 95.24% of the non-CML cases had an absolute basophil count of

Roles of Inflammatory Biomarkers in Exhaled Breath Condensates in Respiratory Clinical Fields.

Exhaled condensates contain inflammatory biomarkers; however, their roles in the clinical field have been under-investigated. We prospectively enrolled subjects admitted to pulmonology clinics. We collected exhaled breath condensates (EBC) and analysed the levels of six and 12 biomarkers using conventional and multiplex enzyme-linked immunosorbent assay, respectively. Among the 123 subjects, healthy controls constituted the largest group (81 participants; 65.9%), followed by the preserved ratio impaired spirometry group (21 patients; 17.1%) and the chronic obstructive pulmonary disease (COPD) group (21 patients; 17.1%). In COPD patients, platelet derived growth factor-AA exhibited strong positive correlations with COPD assessment test (ρ=0.5926, p=0.0423) and COPD-specific version of St. George's Respiratory Questionnaire (SGRQ-C) score (total, ρ=0.6725, p=0.0166; activity, ρ=0.7176, p=0.0086; and impacts, ρ=0.6151, p=0.0333). Granzyme B showed strong positive correlations with SGRQ-C score (symptoms, ρ=0.6078, p=0.0360; and impacts, ρ=0.6007, p=0.0389). Interleukin 6 exhibited a strong positive correlation with SGRQ-C score (activity, ρ=0.4671, p=0.0378). The absolute serum eosinophil and basophil counts showed positive correlations with pro-collagen I alpha 1 (ρ=0.6735, p=0.0164 and ρ=0.6295, p=0.0283, respectively). In healthy subjects, forced expiratory volume in 1 second (FEV1)/forced vital capacity demonstrated significant correlation with CC chemokine ligand 3 (CCL3)/macrophage inflammatory protein 1 alpha (ρ=0.3897 and p=0.0068). FEV1 exhibited significant correlation with CCL11/eotaxin (ρ=0.4445 and p=0.0017). Inflammatory biomarkers in EBC might be useful to predict quality of life concerning respiratory symptoms and serologic markers. Further studies are needed.

THU031 White Blood Cells (WBC) As Biological Markers Of Cortisol Status In Patients With Cushing's Disease (CD)

Abstract Disclosure: B.M. Mascarenhas-Nakano: None. P.F. Santos-Neto: None. L.C. Portari: None. S.R. Correa-Silva: None. J. Abucham: None. CD is a rare disease caused by ACTH-secreting pituitary adenomas and responsible for ∼80% of cases of endogenous hypercortisolism. Hypercortisolism affects all tissues, leading to several nonspecific and few specific anatomical and functional changes which are not always easy to recognize and quantify. Clinical suspicion is the first step in the diagnosis but is rather impressionistic. The influence of endogenous cortisol on WBC, recognized a long time ago, has been widely forgotten/ignored in clinical practice. In this study, we aimed to assess the potential of WBC as biological markers of cortisol status in patients with CD. Patients and Methods: We retrospectively compared Leukocyte (Le), Neutrophil (Ne), Lymphocyte (Ly), Monocyte (Mo), Eosinophil (Eo), and Basophil (Ba) counts at diagnosis in patients with proven CD (CDdx, n=64), at remission after treatment (pituitary surgery, adrenalectomy, or radiotherapy) (CDrem=36), and in a control group of patients with hypercortisolism suspected and ruled out using ES guidelines (CT, n=63). In addition, we retro-prospectively evaluated WBC in a subgroup of 33 patients before and after treatment [25 in remission (RE) and 8 in non-remission (NRE)]. Comparisons &amp;gt;2 groups: ANOVA followed by multiple comparison tests (MCT). Before vs after comparisons: paired tests. Variations (Δ= after-before) between different groups: unpaired tests. Associations: Fisher´s exact test. ROC curves were generated cut off values chosen by Youden index. Significance was set at 0.05. Results: At Diagnosis. Le, Ne, Ly, and Mo were increased and Ly decreased: CDdx vs CT (0.0075&amp;lt;P&amp;lt;0.0001), CDdx vs CDre (0.0015&amp;lt;P&amp;lt;0.0001), CDre vs CT (0.34&amp;lt;P&amp;lt;0.99). Eo and Ba showed no differences in CDdx vs CT (0.20&amp;lt;P&amp;lt;0.67). Diagnostic ROC curves were significant (0.047&amp;lt;P&amp;lt;0.0001) for all cells and various indexes (ratios and differences). AUC (0.8705), Youden index (0.696)(cut off 3,047), sensitivity (87.3%), specificity (82.26%), PPV (0.83) and NPV (0.86) were all highest for the difference Ne-Ly with overlapping confidence intervals with other indexes. At Remission. In paired analysis, most cells showed significant changes after remission. However, comparisons of Δs between RE and NRE groups were only significant for ΔLy and ΔNe% [nearly significant (P=0.06) for ΔNe%-Ly% and ΔLy%]. Remission was associated with ΔLy&amp;gt;-3 (P=0.0049) and ΔNe%&amp;lt;-12.5% (P=0.0463). Combining both parameters (ΔLy&amp;gt;-3 and/or ΔNe%&amp;lt;-12.5%), a stronger association (P= 0.0001) was found. Evaluation of cortisol status after treatment using the combined criterion was able to identify 21/25 (84%) patients in remission and 8/8(100%) innon-remission. Conclusions: Our results show that WBC, mainly Ne and Ly, are reliable biological markers of cortisol status and potentially useful in different steps of the diagnosis of endogenous hypercortisolism as well as in the follow up of patients with CD after treatment. Presentation: Thursday, June 15, 2023

Immune cell kinetics and antibody response in COVID-19 patients with low-count monoclonal B-cell lymphocytosis.

Low-count monoclonal B-cell lymphocytosis (MBLlo ) has been associated with an underlying immunodeficiency and has recently emerged as a new risk factor for severe COVID-19. Here, we investigated the kinetics of immune cell and antibody responses in blood during COVID-19 of MBLlo versus non-MBL patients. For this study, we analyzed the kinetics of immune cells in blood of 336 COVID-19 patients (74 MBLlo and 262 non-MBL), who had not been vaccinated against SARS-CoV-2, over a period of 43 weeks since the onset of infection, using high-sensitivity flow cytometry. Plasma levels of anti-SARS-CoV-2 antibodies were measured in parallel by ELISA. Overall, early after the onset of symptoms, MBLlo COVID-19 patients showed increased neutrophil, monocyte, and particularly, plasma cell (PC) counts, whereas eosinophil, dendritic cell, basophil, and lymphocyte counts were markedly decreased in blood of a variable percentage of samples, and with a tendency toward normal levels from week +5 of infection onward. Compared with non-MBL patients, MBLlo COVID-19 patients presented higher neutrophil counts, together with decreased pre-GC B-cell, dendritic cell, and innate-like T-cell counts. Higher PC levels, together with a delayed PC peak and greater plasma levels of anti-SARS-CoV-2-specific antibodies (at week +2 to week +4) were also observed in MBLlo patients. In summary, MBLlo COVID-19 patients share immune profiles previously described for patients with severe SARS-CoV-2 infection, associated with a delayed but more pronounced PC and antibody humoral response once compared with non-MBL patients.