Journal of Clinical Laboratory Analysis最新文献_第5页

Importance of CD71+ Erythrocyte Cell Levels in Prognosis in Patients With β-Thalassemia CD71+红细胞水平对β-地中海贫血患者预后的重要性

IF 2.6 4区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Journal of Clinical Laboratory Analysis

Pub Date : 2024-06-26 DOI: 10.1002/jcla.25084

Gizem Zorlu Görgülügil, Ayşegül Uğur Kurtoğlu, Sevcan Uğur, Erdal Kurtoğlu

Background/Objectives

CD71⁺ erythroid cells (CECs) are immature red blood cells (proerythroblasts, erythroblasts, and reticulocytes). CECs play an important role in the development of sepsis and cancer by causing immunosuppression. We examined the CEC levels in the peripheral blood of beta thalassemia (βThal) patients and investigated the relationship between CECs and the clinical status of the patients, especially splenectomy.

Methods

Sixty-eight patients with βThal (46 splenectomized and 22 nonsplenectomized) and 15 healthy controls were included in this study. The hemogram parameters, ferritin, and CECs (flow cytometry method) were measured.

Results

It was observed that the CEC level in the patient group was significantly higher than the control group (p < 0.05). CEC levels were found to be significantly higher in patients with splenectomy than in patients with nonsplenectomy (p < 0.05). CEC levels were higher in patients with nontransfusion-dependent βT (NTD-βThal) than in patients with transfusion-dependent βT (TD-βThal) (p < 0.05). CEC levels were found to be significantly higher in patients with splenectomy than in patients with nonsplenectomy in both TD-βThal and NTD-βThal groups (p < 0.05). There was a moderate-negative correlation was detected between CECs and Hb levels (r = −0.467; p < 0.05).

Conclusions

High CEC levels in βThal patients develop as a result of ineffective erythropoiesis. We think that keeping CEC levels under control is important for prognosis, especially in patients with splenectomy.

背景/目的：CD71+ 红细胞（CECs）是未成熟红细胞（原红细胞、红细胞和网织红细胞）。CEC 通过引起免疫抑制，在败血症和癌症的发生发展中发挥着重要作用。我们检测了β地中海贫血（βThal）患者外周血中的CEC水平，并研究了CEC与患者临床状况（尤其是脾切除术）之间的关系：本研究共纳入 68 名β地中海贫血患者（46 名脾切除患者和 22 名非脾切除患者）和 15 名健康对照者。研究人员对血液图参数、铁蛋白和 CECs（流式细胞术法）进行了测量：结果显示：患者组的 CEC 水平明显高于对照组（Pβ-Thal患者的高CEC水平是红细胞生成无效的结果。我们认为，控制 CEC 水平对预后非常重要，尤其是对接受脾切除术的患者。

{"title":"Importance of CD71+ Erythrocyte Cell Levels in Prognosis in Patients With β-Thalassemia","authors":"Gizem Zorlu Görgülügil, Ayşegül Uğur Kurtoğlu, Sevcan Uğur, Erdal Kurtoğlu","doi":"10.1002/jcla.25084","DOIUrl":"10.1002/jcla.25084","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background/Objectives</h3>\u0000 \u0000 <p>CD71<sup>+</sup> erythroid cells (CECs) are immature red blood cells (proerythroblasts, erythroblasts, and reticulocytes). CECs play an important role in the development of sepsis and cancer by causing immunosuppression. We examined the CEC levels in the peripheral blood of beta thalassemia (βThal) patients and investigated the relationship between CECs and the clinical status of the patients, especially splenectomy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Sixty-eight patients with βThal (46 splenectomized and 22 nonsplenectomized) and 15 healthy controls were included in this study. The hemogram parameters, ferritin, and CECs (flow cytometry method) were measured.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>It was observed that the CEC level in the patient group was significantly higher than the control group (<i>p</i> < 0.05). CEC levels were found to be significantly higher in patients with splenectomy than in patients with nonsplenectomy (<i>p</i> < 0.05). CEC levels were higher in patients with nontransfusion-dependent βT (NTD-βThal) than in patients with transfusion-dependent βT (TD-βThal) (<i>p</i> < 0.05). CEC levels were found to be significantly higher in patients with splenectomy than in patients with nonsplenectomy in both TD-βThal and NTD-βThal groups (<i>p</i> < 0.05). There was a moderate-negative correlation was detected between CECs and Hb levels (<i>r</i> = −0.467; <i>p</i> < 0.05).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>High CEC levels in βThal patients develop as a result of ineffective erythropoiesis. We think that keeping CEC levels under control is important for prognosis, especially in patients with splenectomy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15509,"journal":{"name":"Journal of Clinical Laboratory Analysis","volume":"38 11-12","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcla.25084","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141457172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Identification of a Novel Deletion Variant (c.2999_3005delTGTGTGT/p.Asn1000SerfsTer4) in NPHP4 Associated With Nephronophthisis-4 鉴定与肾炎-4（Nephronophthisis-4）相关的 NPHP4 中一个新的缺失变异（c.2999_3005delTGTGTGT/p.Asn1000SerfsTer4）。

IF 2.6 4区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Journal of Clinical Laboratory Analysis

Pub Date : 2024-06-19 DOI: 10.1002/jcla.25077

Zahra Miri Karam, Atieh Karimi Gohari, Mohammad Javad Rezazadeh Khabaz, Abolfazl Yari, Seyed Mahdi Emami Meybodi, Rezvan Attari, Maryam Torabi, Farzane Vafaeie, Fateme Moradi Moraddahande, Sara Amiri, Kolsoum Saeidi

Background

Nephronophthisis-4 (NPHP4) is an inherited renal ciliopathy described by renal fibrosis and progressive impairment of kidney function. This study aimed to investigate the genetic basis and clinical manifestations of NPHP4 in two Iranian siblings.

Methods

The proband was a 27-year-old male with features of end-stage renal disease, including anemia, uremia, polyuria, and polydipsia. It is worth mentioning that he has a 22-year-old sister with a similar presentation. Clinical diagnosis procedures, such as renal biopsy, brain imaging, blood and urine tests, cardiac evaluation, ophthalmic inspection, and auditory function assessment, were carried out to evaluate organ involvement and potential comorbidities. Whole-exome sequencing (WES) and segregation analysis were performed to identify and confirm genetic variants associated with the condition. Computational variant analysis was conducted to evaluate the pathogenicity of the candidate variant. Furthermore, the SWISS-MODEL server was utilized for protein modeling.

Results

The brain, cardiac, ocular, and auditory functions were normal. Renal biopsy of the proband showed chronic interstitial inflammation and fibrosis. We found a novel homozygous 7-base pair deletion (c.2999_3005delTGTGTGT/ p.Asn1000SerfsTer4) in exon 21 of NPHP4 by WES. Segregation analysis confirmed homozygosity for the NPHP4 variant in affected individuals and heterozygous carrier status in parents, supporting autosomal recessive inheritance. 3D protein modeling indicated significant structural changes due to the variant.

Conclusion

This study expands the genetic causes and phenotypic spectrum of nephronophthisis-4 and reveals the importance of genetic analysis in diagnosing and managing rare inherited kidney disorders, particularly those involving consanguinity.

背景：肾炎-4（Nephronophthis-4，NPHP4）是一种遗传性肾纤毛病，表现为肾脏纤维化和进行性肾功能损害。本研究旨在调查两个伊朗兄弟姐妹中 NPHP4 的遗传基础和临床表现：原发性肾病患者是一名 27 岁的男性，具有终末期肾病的特征，包括贫血、尿毒症、多尿和多饮。值得一提的是，他有一个 22 岁的妹妹也有类似表现。临床诊断程序包括肾活检、脑成像、血液和尿液检查、心脏评估、眼科检查和听觉功能评估，以评估器官受累情况和潜在的合并症。进行了全外显子组测序（WES）和分离分析，以识别和确认与该疾病相关的基因变异。还进行了计算变异分析，以评估候选变异的致病性。此外，还利用 SWISS-MODEL 服务器进行了蛋白质建模：大脑、心脏、眼睛和听觉功能正常。该患者的肾活检结果显示存在慢性间质性炎症和纤维化。我们通过WES发现NPHP4第21外显子存在一个新的7碱基对同源缺失（c.2999_3005delTGTGTGT/ p.Asn1000SerfsTer4）。分离分析证实，患者为 NPHP4 变体的同基因携带者，其父母为杂合子携带者，支持常染色体隐性遗传。三维蛋白质建模显示，该变异体导致了明显的结构变化：本研究拓展了肾炎-4 的遗传原因和表型谱，揭示了遗传分析在诊断和管理罕见遗传性肾脏疾病，尤其是涉及近亲结婚的疾病中的重要性。

{"title":"Identification of a Novel Deletion Variant (c.2999_3005delTGTGTGT/p.Asn1000SerfsTer4) in NPHP4 Associated With Nephronophthisis-4","authors":"Zahra Miri Karam, Atieh Karimi Gohari, Mohammad Javad Rezazadeh Khabaz, Abolfazl Yari, Seyed Mahdi Emami Meybodi, Rezvan Attari, Maryam Torabi, Farzane Vafaeie, Fateme Moradi Moraddahande, Sara Amiri, Kolsoum Saeidi","doi":"10.1002/jcla.25077","DOIUrl":"10.1002/jcla.25077","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Nephronophthisis-4 (NPHP4) is an inherited renal ciliopathy described by renal fibrosis and progressive impairment of kidney function. This study aimed to investigate the genetic basis and clinical manifestations of NPHP4 in two Iranian siblings.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The proband was a 27-year-old male with features of end-stage renal disease, including anemia, uremia, polyuria, and polydipsia. It is worth mentioning that he has a 22-year-old sister with a similar presentation. Clinical diagnosis procedures, such as renal biopsy, brain imaging, blood and urine tests, cardiac evaluation, ophthalmic inspection, and auditory function assessment, were carried out to evaluate organ involvement and potential comorbidities. Whole-exome sequencing (WES) and segregation analysis were performed to identify and confirm genetic variants associated with the condition. Computational variant analysis was conducted to evaluate the pathogenicity of the candidate variant. Furthermore, the SWISS-MODEL server was utilized for protein modeling.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The brain, cardiac, ocular, and auditory functions were normal. Renal biopsy of the proband showed chronic interstitial inflammation and fibrosis. We found a novel homozygous 7-base pair deletion (c.2999_3005delTGTGTGT/ p.Asn1000SerfsTer4) in exon 21 of <i>NPHP4</i> by WES. Segregation analysis confirmed homozygosity for the NPHP4 variant in affected individuals and heterozygous carrier status in parents, supporting autosomal recessive inheritance. 3D protein modeling indicated significant structural changes due to the variant.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study expands the genetic causes and phenotypic spectrum of nephronophthisis-4 and reveals the importance of genetic analysis in diagnosing and managing rare inherited kidney disorders, particularly those involving consanguinity.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15509,"journal":{"name":"Journal of Clinical Laboratory Analysis","volume":"38 11-12","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcla.25077","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141419363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Rising Tide of Antibiotic Resistance: A Study on Extended-Spectrum Beta-Lactamase and Carbapenem-Resistant Escherichia coli and Klebsiella pneumoniae 抗生素耐药性的浪潮：对广谱β-内酰胺酶和碳青霉烯耐药大肠埃希菌和肺炎克雷伯菌的研究。

IF 2.6 4区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Journal of Clinical Laboratory Analysis

Pub Date : 2024-06-17 DOI: 10.1002/jcla.25081

Hasan Ejaz, Muhammad Usman Qamar, Aisha Farhana, Sonia Younas, Alia Batool, Durreshahwar Lone, Muhammad Atif, Mashael W. Alruways, Muharib Alruwaili, Ismail Hamad, Samy Selim, Bi Bi Zainab Mazhari, Ali Farooq, Kashaf Junaid

Background

The global spread of extended-spectrum beta-lactamase (ESBL)-producing and carbapenem-resistant Enterobacterales (CRE) poses a significant concern. Acquisition of antimicrobial resistance genes leads to resistance against several antibiotics, limiting treatment options. We aimed to study ESBL-producing and CRE transmission in clinical settings.

Methods

From clinical samples, 227 ESBL-producing and CRE isolates were obtained. The isolates were cultured on bacterial media and confirmed by VITEK 2. Antibiograms were tested against several antibiotics using VITEK 2. The acquired resistance genes were identified by PCR.

Results

Of the 227 clinical isolates, 145 (63.8%) were Klebsiella pneumoniae and 82 (36.1%) were Escherichia coli; 76 (33.4%) isolates were detected in urine, 57 (25.1%) in pus swabs, and 53 (23.3%) in blood samples. A total of 58 (70.7%) ESBL-producing E. coli were resistant to beta-lactams, except for carbapenems, and 17.2% were amikacin-resistant; 29.2% of E. coli isolates were resistant to carbapenems. A total of 106 (73.1%) ESBL-producing K. pneumoniae were resistant to all beta-lactams, except for carbapenems, and 66.9% to ciprofloxacin; 38 (26.2%) K. pneumoniae were resistant to carbapenems. Colistin emerged as the most effective antibiotic against both bacterial types. Twelve (20.6%) E. coli isolates were positive for bla_CTX-M, 11 (18.9%) for bla_TEM, and 8 (33.3%) for bla_NDM. Forty-six (52.3%) K. pneumoniae isolates had bla_CTX-M, 27 (18.6%) bla_TEM, and 26 (68.4%) bla_NDM.

Conclusion

This study found a high prevalence of drug-resistant ESBL-producing and CRE, highlighting the need for targeted antibiotic use to combat resistance.

背景：产广谱β-内酰胺酶（ESBL）和耐碳青霉烯类肠杆菌（CRE）在全球的蔓延引起了人们的极大关注。抗菌药耐药性基因的获得会导致对多种抗生素产生耐药性，从而限制了治疗方案的选择。我们旨在研究 ESBL 产菌和 CRE 在临床环境中的传播情况：方法：从临床样本中获得 227 株产 ESBL 和 CRE 分离物。用 VITEK 2 对几种抗生素进行抗菌谱检测，并通过 PCR 鉴定获得的耐药基因：在 227 例临床分离菌中，145 例（63.8%）为肺炎克雷伯菌，82 例（36.1%）为大肠埃希菌；76 例（33.4%）从尿液中分离，57 例（25.1%）从脓拭子中分离，53 例（23.3%）从血液样本中分离。共有 58 个（70.7%）产生 ESBL 的大肠埃希氏菌对β-内酰胺类药物（碳青霉烯类除外）耐药，17.2% 的大肠埃希氏菌对阿米卡星耐药；29.2% 的大肠埃希氏菌对碳青霉烯类耐药。共有 106 株（73.1%）产生 ESBL 的肺炎双球菌对除碳青霉烯类以外的所有β-内酰胺类药物耐药，66.9%对环丙沙星耐药；38 株（26.2%）肺炎双球菌对碳青霉烯类耐药。可乐定是对这两种细菌类型最有效的抗生素。有 12 个（20.6%）大肠杆菌分离物对 blaCTX-M 呈阳性，11 个（18.9%）对 blaTEM 呈阳性，8 个（33.3%）对 blaNDM 呈阳性。46例（52.3%）肺炎克雷伯菌分离物对 blaCTX-M 呈阳性，27 例（18.6%）对 blaTEM 呈阳性，26 例（68.4%）对 blaNDM 呈阳性：结论：本研究发现耐药性 ESBL 产物和 CRE 的流行率很高，这凸显了有针对性地使用抗生素来对抗耐药性的必要性。

{"title":"The Rising Tide of Antibiotic Resistance: A Study on Extended-Spectrum Beta-Lactamase and Carbapenem-Resistant Escherichia coli and Klebsiella pneumoniae","authors":"Hasan Ejaz, Muhammad Usman Qamar, Aisha Farhana, Sonia Younas, Alia Batool, Durreshahwar Lone, Muhammad Atif, Mashael W. Alruways, Muharib Alruwaili, Ismail Hamad, Samy Selim, Bi Bi Zainab Mazhari, Ali Farooq, Kashaf Junaid","doi":"10.1002/jcla.25081","DOIUrl":"10.1002/jcla.25081","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The global spread of extended-spectrum beta-lactamase (ESBL)-producing and carbapenem-resistant Enterobacterales (CRE) poses a significant concern. Acquisition of antimicrobial resistance genes leads to resistance against several antibiotics, limiting treatment options. We aimed to study ESBL-producing and CRE transmission in clinical settings.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>From clinical samples, 227 ESBL-producing and CRE isolates were obtained. The isolates were cultured on bacterial media and confirmed by VITEK 2. Antibiograms were tested against several antibiotics using VITEK 2. The acquired resistance genes were identified by PCR.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of the 227 clinical isolates, 145 (63.8%) were <i>Klebsiella pneumoniae</i> and 82 (36.1%) were <i>Escherichia coli</i>; 76 (33.4%) isolates were detected in urine, 57 (25.1%) in pus swabs, and 53 (23.3%) in blood samples. A total of 58 (70.7%) ESBL-producing <i>E. coli</i> were resistant to beta-lactams, except for carbapenems, and 17.2% were amikacin-resistant; 29.2% of <i>E. coli</i> isolates were resistant to carbapenems. A total of 106 (73.1%) ESBL-producing <i>K. pneumoniae</i> were resistant to all beta-lactams, except for carbapenems, and 66.9% to ciprofloxacin; 38 (26.2%) <i>K. pneumoniae</i> were resistant to carbapenems. Colistin emerged as the most effective antibiotic against both bacterial types. Twelve (20.6%) <i>E. coli</i> isolates were positive for <i>bla</i><sub>CTX-M</sub>, 11 (18.9%) for <i>bla</i><sub>TEM</sub>, and 8 (33.3%) for <i>bla</i><sub>NDM</sub>. Forty-six (52.3%) <i>K. pneumoniae</i> isolates had <i>bla</i><sub>CTX-M</sub>, 27 (18.6%) <i>bla</i><sub>TEM</sub>, and 26 (68.4%) <i>bla</i><sub>NDM</sub>.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study found a high prevalence of drug-resistant ESBL-producing and CRE, highlighting the need for targeted antibiotic use to combat resistance.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15509,"journal":{"name":"Journal of Clinical Laboratory Analysis","volume":"38 10","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11211664/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141331068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Novel Germline KIT Variants in Families With Severe Piebaldism: Case Series and Literature Review 重度胼胝体畸形家族中的新型基因 KIT 变异：病例系列和文献综述

IF 2.6 4区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Journal of Clinical Laboratory Analysis

Pub Date : 2024-06-17 DOI: 10.1002/jcla.25073

Yuanyuan Zhang, Haiming Gao, Lu Zhang, Yunjing Zhao, Chuang Qiu, Xiaoliang Liu

Introduction

Piebaldism is a rare autosomal dominant disorder characterized by congenital white forelock and depigmented patches, which is most commonly caused by deleterious variants in the KIT gene.

Methods

Four KIT variants were identified in a piebaldism case series by whole-exome sequencing. Functional experiments, including in vitro minigene reporter assay and enzyme-linked immunosorbent assay, were carried out to elucidate the pathogenicity of the variants. The genotype–phenotype correlation was summarized through extensive literature reviewing.

Results

All the four cases had severe piebaldism presented with typical white forelock and diffuse depigmentation on the ventral trunk and limbs. Four germline variants at the tyrosine kinase (TK) domains of the KIT gene were identified: two novel variants c.1990+1G>A (p.Pro627_Gly664delinsArg) and c.2716T>C (p.Cys906Arg), and two known variants c.1879+1G>A (p.Gly592_Pro627delinsAla) and c.1747G>A (p.Glu583Lys). Both splicing variants caused exon skipping and inframe deletions in the TK1 domain. The missense variants resided at the TK1 and TK2 domains respectively impairing PI3K/AKT and MAPK/ERK signaling pathways, the downstream of KIT. All severe cases were associated with variants in the TK domains, eliciting a major dominant-negative mechanism of the disease.

Conclusion

Our data expand the mutation spectrum of KIT, emphasized by a dominant-negative effect of variants in the critical TK domains in severe cases. We also share the experience of prenatal diagnosis and informed reproductive choices for the affected families.

简介骓斑症是一种罕见的常染色体显性遗传疾病，以先天性白前额和色素脱失斑为特征，最常见的病因是 KIT 基因中的有害变体：方法：通过全外显子组测序，在派秃症病例系列中发现了四个 KIT 变异基因。方法：通过全外显子组测序在一个胼胝体畸形病例系列中发现了四个 KIT 变异基因，并进行了功能实验，包括体外微型基因报告实验和酶联免疫吸附实验，以阐明这些变异基因的致病性。通过查阅大量文献，总结了基因型与表型的相关性：结果：四例病例均患有严重的骓症，表现为典型的白色前锁，躯干和四肢腹侧有弥漫性色素沉着。研究发现了 KIT 基因酪氨酸激酶（TK）结构域的四个种系变异：两个新变异 c.1990+1G>A（p.Pro627_Gly664delinsArg）和 c.2716T>C（p.Cys906Arg），以及两个已知变异 c.1879+1G>A（p.Gly592_Pro627delinsAla）和 c.1747G>A（p.Glu583Lys）。这两种剪接变异都会导致外显子跳过和 TK1 结构域的内切缺失。错义变体分别位于TK1和TK2结构域，损害了KIT下游的PI3K/AKT和MAPK/ERK信号通路。所有重症病例都与TK结构域的变异有关，从而引发了一种主要的显性阴性疾病机制：我们的数据扩大了 KIT 的突变谱，强调了严重病例中关键 TK 结构域变异的显性负效应。我们还分享了产前诊断的经验以及受影响家庭的知情生育选择。

{"title":"Novel Germline KIT Variants in Families With Severe Piebaldism: Case Series and Literature Review","authors":"Yuanyuan Zhang, Haiming Gao, Lu Zhang, Yunjing Zhao, Chuang Qiu, Xiaoliang Liu","doi":"10.1002/jcla.25073","DOIUrl":"10.1002/jcla.25073","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Piebaldism is a rare autosomal dominant disorder characterized by congenital white forelock and depigmented patches, which is most commonly caused by deleterious variants in the <i>KIT</i> gene.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Four <i>KIT</i> variants were identified in a piebaldism case series by whole-exome sequencing. Functional experiments, including in vitro minigene reporter assay and enzyme-linked immunosorbent assay, were carried out to elucidate the pathogenicity of the variants. The genotype–phenotype correlation was summarized through extensive literature reviewing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>All the four cases had severe piebaldism presented with typical white forelock and diffuse depigmentation on the ventral trunk and limbs. Four germline variants at the tyrosine kinase (TK) domains of the <i>KIT</i> gene were identified: two novel variants c.1990+1G>A (p.Pro627_Gly664delinsArg) and c.2716T>C (p.Cys906Arg), and two known variants c.1879+1G>A (p.Gly592_Pro627delinsAla) and c.1747G>A (p.Glu583Lys). Both splicing variants caused exon skipping and inframe deletions in the TK1 domain. The missense variants resided at the TK1 and TK2 domains respectively impairing PI3K/AKT and MAPK/ERK signaling pathways, the downstream of KIT. All severe cases were associated with variants in the TK domains, eliciting a major dominant-negative mechanism of the disease.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our data expand the mutation spectrum of <i>KIT</i>, emphasized by a dominant-negative effect of variants in the critical TK domains in severe cases. We also share the experience of prenatal diagnosis and informed reproductive choices for the affected families.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15509,"journal":{"name":"Journal of Clinical Laboratory Analysis","volume":"38 11-12","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcla.25073","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141419319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Antibody–Antibiotic Conjugates: A Comprehensive Review on Their Therapeutic Potentials Against BacterialInfections 抗体-抗生素共轭物：抗体-抗生素共轭物：抗细菌感染治疗潜力综述》（Antibody-Antibotic Conjugates: A Comprehensive Review on Their Treatment Potentials Against BacterialInfections.

IF 2.6 4区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Journal of Clinical Laboratory Analysis

Pub Date : 2024-06-13 DOI: 10.1002/jcla.25071

Atieh Darbandi, Milad Abdi, Shirin Dashtbin, Sajad Yaghoubi, Mohammad Sholeh, Ebrahim Kouhsari, Talieh Darbandi, Roya Ghanavati, Behrouz Taheri

Introduction

Antibodies are significant agents in the immune system and have proven to be effective in treating bacterial infections. With the advancement of antibody engineering in recent decades, antibody therapy has evolved widely.

Aim

This review aimed to investigate a new method as a therapeutic platform for the treatment of bacterial infections and explore the novel features of this method in conferring pathogen specificity to broad-spectrum antibiotics.

Material and Methods

A literature review was conducted addressing the following topics about antibody–antibiotic conjugates (AACs): (1) structure and mechanism of action; (2) clinical effectiveness; (3) advantages and disadvantages.

Result

Antibody conjugates are designed to build upon the progress made in the development of monoclonal antibodies for the treatment of diseases. Despite the growing emergence of antibiotic resistance among pathogenic bacteria worldwide, novel antimicrobials have not been sufficiently expanded to combat the global crisis of antibiotic resistance. A recently developed strategy for the treatment of infectious diseases is the use of AACs, which are specifically activated only in host cells.

Conclusion

A novel therapeutic AAC employs an antibody to deliver the antibiotic to the bacteria. The AACs can release potent antibacterial components that unconjugated forms may not exhibit with an appropriate therapeutic index. This review highlights how this science has guided the design principles of an impressive AAC and discusses how the AAC model promises to enhance the antibiotic effect against bacterial infections.

引言抗体是免疫系统中的重要物质，已被证明能有效治疗细菌感染。目的：本综述旨在研究一种作为细菌感染治疗平台的新方法，并探讨该方法在赋予广谱抗生素病原体特异性方面的新特点：对抗体-抗生素共轭物（AACs）的以下内容进行了文献综述：(1) 结构和作用机制；(2) 临床效果；(3) 优缺点：抗体共轭物是在单克隆抗体治疗疾病的发展基础上设计的。尽管全球病原菌对抗生素的耐药性日益突出，但新型抗菌药物尚未得到充分推广，以应对全球抗生素耐药性危机。最近开发的一种治疗传染病的策略是使用 AAC，这种抗体只在宿主细胞中被特异性激活：结论：一种新型治疗性 AAC 利用抗体将抗生素传递给细菌。AACs 可以释放出有效的抗菌成分，而非结合型的 AACs 可能无法显示出适当的治疗指数。本综述重点介绍了这一科学如何指导令人印象深刻的 AAC 的设计原则，并讨论了 AAC 模型如何有望增强抗生素对细菌感染的效果。

{"title":"Antibody–Antibiotic Conjugates: A Comprehensive Review on Their Therapeutic Potentials Against BacterialInfections","authors":"Atieh Darbandi, Milad Abdi, Shirin Dashtbin, Sajad Yaghoubi, Mohammad Sholeh, Ebrahim Kouhsari, Talieh Darbandi, Roya Ghanavati, Behrouz Taheri","doi":"10.1002/jcla.25071","DOIUrl":"10.1002/jcla.25071","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Antibodies are significant agents in the immune system and have proven to be effective in treating bacterial infections. With the advancement of antibody engineering in recent decades, antibody therapy has evolved widely.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>This review aimed to investigate a new method as a therapeutic platform for the treatment of bacterial infections and explore the novel features of this method in conferring pathogen specificity to broad-spectrum antibiotics.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Material and Methods</h3>\u0000 \u0000 <p>A literature review was conducted addressing the following topics about antibody–antibiotic conjugates (AACs): (1) structure and mechanism of action; (2) clinical effectiveness; (3) advantages and disadvantages.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Result</h3>\u0000 \u0000 <p>Antibody conjugates are designed to build upon the progress made in the development of monoclonal antibodies for the treatment of diseases. Despite the growing emergence of antibiotic resistance among pathogenic bacteria worldwide, novel antimicrobials have not been sufficiently expanded to combat the global crisis of antibiotic resistance. A recently developed strategy for the treatment of infectious diseases is the use of AACs, which are specifically activated only in host cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>A novel therapeutic AAC employs an antibody to deliver the antibiotic to the bacteria. The AACs can release potent antibacterial components that unconjugated forms may not exhibit with an appropriate therapeutic index. This review highlights how this science has guided the design principles of an impressive AAC and discusses how the AAC model promises to enhance the antibiotic effect against bacterial infections.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15509,"journal":{"name":"Journal of Clinical Laboratory Analysis","volume":"38 10","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11211676/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141310821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Soluble Fibrinogen–Like Protein 2 Downregulation and Th17/Treg Imbalance in a Taurocholate-Induced Murine Experimental Model of Severe Acute Pancreatitis 陶罗胆酸诱导的小鼠重症急性胰腺炎实验模型中可溶性纤维蛋白原样蛋白 2 的下调与 Th17/Treg 失衡

IF 2.6 4区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Journal of Clinical Laboratory Analysis

Pub Date : 2024-06-09 DOI: 10.1002/jcla.25076

Yibing Hu, Jin Ding, Yanping Chen, Qunying Wang, Xiaoyun Yang, Hongjun Hua, Xiaohua Ye

Background

Severe acute pancreatitis (SAP) is associated with tremendous systemic inflammation, T-helper 17 (Th17) cells, and regulatory T (Treg) cells play an essential role in the inflammatory responses. Meanwhile, soluble fibrinogen–like protein 2 (Sfgl2) is a critical immunosuppressive effector cytokine of Treg cells and modulates immune responses. However, the impact of SAP induction on Sfgl2 expression and the role of Sfgl2 in immunomodulation under SAP conditions are largely unknown.

Methods

A taurocholate-induced mouse SAP model was established. The ratios of CD4⁺CD25⁺Foxp3⁺ Treg cells or CD4⁺IL-17⁺ Th17 cells in blood and pancreatic tissues as well as surface expression of CD80, CD86, and major histocompatibility complex class II (MHC-II) were determined by flow cytometry. Gene mRNA expression was determined by qPCR. Serum amylase and soluble factors were quantitated by commercial kits. Bone marrow–derived dendritic cells (DCs) were generated, and NF-κB/p65 translocation was measured by immunofluorescence staining.

Results

SAP induction in mice decreased the Th17/Treg ratio in the pancreatic tissue and increased the Th17/Treg ratio in the peripheral blood. In addition, SAP was associated with a reduced level of Sfgl2 in the pancreatic tissue and blood: higher levels of serum IL-17, IL-2, IFN-α, and TNF-α, and lower levels of serum IL-4 and IL-10. Furthermore, the SAP-induced reduction in Sfgl2 expression was accompanied by dysregulated maturation of bone marrow–derived DCs.

Conclusions

SAP causes reduced Sfgl2 expression and Th17/Treg imbalance, thus providing critical insights for the development of Sfgl2- and Th17/Treg balance-targeted immunotherapies for patients with SAP.

背景：重症急性胰腺炎（SAP）与巨大的全身性炎症有关，T-helper 17（Th17）细胞和调节性T（Treg）细胞在炎症反应中起着至关重要的作用。同时，可溶性纤维蛋白原样蛋白 2（Sfgl2）是 Treg 细胞的一种重要的免疫抑制效应细胞因子，可调节免疫反应。然而，SAP诱导对Sfgl2表达的影响以及Sfgl2在SAP条件下免疫调节中的作用目前尚不清楚：方法：建立了牛磺胆酸盐诱导的小鼠SAP模型。方法：通过流式细胞术测定血液和胰腺组织中 CD4+CD25+Foxp3+ Treg 细胞或 CD4+IL-17+ Th17 细胞的比例，以及 CD80、CD86 和主要组织相容性复合体 II 类（MHC-II）的表面表达。基因 mRNA 表达通过 qPCR 进行测定。血清淀粉酶和可溶性因子用商业试剂盒定量。生成骨髓树突状细胞（DCs），并通过免疫荧光染色测定NF-κB/p65的转位：结果：SAP诱导小鼠降低了胰腺组织中Th17/Treg的比例，增加了外周血中Th17/Treg的比例。此外，SAP与胰腺组织和血液中Sfgl2水平降低有关：血清IL-17、IL-2、IFN-α和TNF-α水平升高，血清IL-4和IL-10水平降低。此外，SAP诱导的Sfgl2表达量减少还伴随着骨髓源性DC的成熟失调：结论：SAP会导致Sfgl2表达减少和Th17/Treg失衡，从而为开发针对SAP患者的Sfgl2-和Th17/Treg平衡的免疫疗法提供重要启示。

{"title":"Soluble Fibrinogen–Like Protein 2 Downregulation and Th17/Treg Imbalance in a Taurocholate-Induced Murine Experimental Model of Severe Acute Pancreatitis","authors":"Yibing Hu, Jin Ding, Yanping Chen, Qunying Wang, Xiaoyun Yang, Hongjun Hua, Xiaohua Ye","doi":"10.1002/jcla.25076","DOIUrl":"10.1002/jcla.25076","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Severe acute pancreatitis (SAP) is associated with tremendous systemic inflammation, T-helper 17 (Th17) cells, and regulatory T (Treg) cells play an essential role in the inflammatory responses. Meanwhile, soluble fibrinogen–like protein 2 (Sfgl2) is a critical immunosuppressive effector cytokine of Treg cells and modulates immune responses. However, the impact of SAP induction on Sfgl2 expression and the role of Sfgl2 in immunomodulation under SAP conditions are largely unknown.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A taurocholate-induced mouse SAP model was established. The ratios of CD4<sup>+</sup>CD25<sup>+</sup>Foxp3<sup>+</sup> Treg cells or CD4<sup>+</sup>IL-17<sup>+</sup> Th17 cells in blood and pancreatic tissues as well as surface expression of CD80, CD86, and major histocompatibility complex class II (MHC-II) were determined by flow cytometry. Gene mRNA expression was determined by qPCR. Serum amylase and soluble factors were quantitated by commercial kits. Bone marrow–derived dendritic cells (DCs) were generated, and NF-κB/p65 translocation was measured by immunofluorescence staining.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>SAP induction in mice decreased the Th17/Treg ratio in the pancreatic tissue and increased the Th17/Treg ratio in the peripheral blood. In addition, SAP was associated with a reduced level of Sfgl2 in the pancreatic tissue and blood: higher levels of serum IL-17, IL-2, IFN-α, and TNF-α, and lower levels of serum IL-4 and IL-10. Furthermore, the SAP-induced reduction in Sfgl2 expression was accompanied by dysregulated maturation of bone marrow–derived DCs.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>SAP causes reduced Sfgl2 expression and Th17/Treg imbalance, thus providing critical insights for the development of Sfgl2- and Th17/Treg balance-targeted immunotherapies for patients with SAP.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15509,"journal":{"name":"Journal of Clinical Laboratory Analysis","volume":"38 10","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11211668/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141296149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Establishment of Reference Range for Serum Concentration of Vitamin A and Vitamin E in Southern Sichuan Area of China 中国四川南部地区血清中维生素 A 和维生素 E 浓度参考范围的确定。

IF 2.6 4区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Journal of Clinical Laboratory Analysis

Pub Date : 2024-06-07 DOI: 10.1002/jcla.25074

Qiang Ye, Qiang Zhong, Guoping Huang, Wen Zhang

Objective

To establish the reference range of serum concentration of vitamin A (VA) and vitamin E (VE) in Southern Sichuan area of China.

Methods

From August 1, 2021, to May 31, 2023, 9482 blood tablets were received for the screening of VA and VE. The information was divided into four different age groups: ≤1 year old, 1< to ≤6 years, 6< to ≤17 years, and 17< to ≤59 years. In each age group, the four seasons were further subdivided into spring, summer, autumn, and winter, as well as male and female genders. The serum concentration of VA and VE was detected by liquid chromatography—tandem mass spectrometry (HPLC-MS), and the reference range was established for verification.

Results

The concentration of VA and VE in 9482 cases showed skewed distribution. When comparing between different age groups, the serum concentration of VA and VE was statistically significant (p < 0.05). While comparing different seasons, the serum VA levels in different seasons were significantly different (p < 0.05) except in summer and autumn. There was statistical significance in VE level in different seasons (p < 0.05). And while comparing different genders, there was no statistical significance in VA concentration levels (p > 0.05). The VE concentration levels were statistically significant (p < 0.05). The established reference range was established and verified, and the results were in accordance with the standard.

Conclusion

The reference range of VA and VE should be set according to different ages, different seasons, and different genders.

目的方法：从 2021 年 8 月 1 日至 2023 年 5 月 31 日，在四川南部地区开展血清维生素 A（VA）和维生素 E（VE）浓度的参考范围测定：方法：自 2021 年 8 月 1 日至 2023 年 5 月 31 日，共采集 9482 份血片用于维生素 A 和维生素 E 的筛查。资料分为四个不同年龄组：≤1 岁、1＜～≤6 岁、6＜～≤17 岁、17＜～≤59 岁。每个年龄组又细分为春、夏、秋、冬四个季节和男女性别。采用液相色谱-串联质谱法（HPLC-MS）检测血清中VA和VE的浓度，并建立参考范围进行验证：结果：9482 个病例的 VA 和 VE 浓度呈偏态分布。不同年龄组血清中 VA 和 VE 浓度比较，差异有统计学意义（P 0.05）。VE 浓度水平也有统计学意义（P 结论：VA 和 VE 的参考值范围为 0.05%：应根据不同年龄、不同季节和不同性别设定 VA 和 VE 的参考范围。

{"title":"Establishment of Reference Range for Serum Concentration of Vitamin A and Vitamin E in Southern Sichuan Area of China","authors":"Qiang Ye, Qiang Zhong, Guoping Huang, Wen Zhang","doi":"10.1002/jcla.25074","DOIUrl":"10.1002/jcla.25074","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To establish the reference range of serum concentration of vitamin A (VA) and vitamin E (VE) in Southern Sichuan area of China.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>From August 1, 2021, to May 31, 2023, 9482 blood tablets were received for the screening of VA and VE. The information was divided into four different age groups: ≤1 year old, 1< to ≤6 years, 6< to ≤17 years, and 17< to ≤59 years. In each age group, the four seasons were further subdivided into spring, summer, autumn, and winter, as well as male and female genders. The serum concentration of VA and VE was detected by liquid chromatography—tandem mass spectrometry (HPLC-MS), and the reference range was established for verification.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The concentration of VA and VE in 9482 cases showed skewed distribution. When comparing between different age groups, the serum concentration of VA and VE was statistically significant (<i>p</i> < 0.05). While comparing different seasons, the serum VA levels in different seasons were significantly different (<i>p</i> < 0.05) except in summer and autumn. There was statistical significance in VE level in different seasons (<i>p</i> < 0.05). And while comparing different genders, there was no statistical significance in VA concentration levels (<i>p</i> > 0.05). The VE concentration levels were statistically significant (<i>p</i> < 0.05). The established reference range was established and verified, and the results were in accordance with the standard.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The reference range of VA and VE should be set according to different ages, different seasons, and different genders.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15509,"journal":{"name":"Journal of Clinical Laboratory Analysis","volume":"38 10","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11211669/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141283867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Analytical Interference in Chemiluminescence Assay–Measured Angiotensin I, Angiotensin II, Aldosterone, and Renin 化学发光测定法测量的血管紧张素 I、血管紧张素 II、醛固酮和肾素的分析干扰。

IF 2.6 4区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Journal of Clinical Laboratory Analysis

Pub Date : 2024-06-01 DOI: 10.1002/jcla.25045

Xiaohua Xu, Yongzhi Xu, Shengqiang Liang

Background

The interference can be a significant source of laboratory errors with the potential to cause immunoassay results to drift. Therefore, we evaluated the interference in various endogenous and exogenous substances on immunoassay for angiotensin I (Ang I), angiotensin II (Ang II), aldosterone, and renin in vitro.

Methods

Ten endogenous and eight exogenous substances were evaluated at supraphysiologic or supratherapeutic plasma levels using the screening study to identify potential interfering substances. Subsequently, potential interfering substances were further tested within maximum pathological or therapeutic plasma concentration ranges using the dose–response study to determine whether the interference has a significant bias. According to preset acceptance criteria, the interference in potential interfering substances for Ang I, Ang II, and renin and aldosterone assays was determined.

Results

Six potential interfering substances for Ang I immunoassays were identified, namely valsartan, nifedipine, spironolactone, cholesterol, hemoglobin, and triglyceride. Meanwhile, ethanol, nifedipine, spironolactone, heparin sodium, warfarin, hemoglobin, uric acid, cholesterol, and triglyceride appeared to have potential interference in the Ang II assay. Three identified as possible interferents for aldosterone immunoassays were glucose, valsartan, and spironolactone. Moreover, warfarin, valsartan, spironolactone, uric acid, cholesterol, bilirubin unconjugated, triglyceride, and hemoglobin were potential interfering substances for renin immunoassays. However, only spironolactone of these potential interfering substances exceeded preset mean bias limits (less than ±10.0%) in aldosterone immunoassays.

Conclusion

Exogenous spironolactone caused clinically significant interference in aldosterone immunoassays. Moreover, the interference in other substances was acceptable in Ang I, Ang II, and renin and aldosterone immunoassays.

背景：干扰是实验室误差的一个重要来源，有可能导致免疫测定结果漂移。因此，我们评估了各种内源性和外源性物质对体外血管紧张素 I（Ang I）、血管紧张素 II（Ang II）、醛固酮和肾素免疫测定的干扰：采用筛选研究法评估了超生理或超治疗血浆水平的 10 种内源性物质和 8 种外源性物质，以确定潜在的干扰物质。随后，利用剂量反应研究在最大病理或治疗血浆浓度范围内对潜在干扰物质进行进一步测试，以确定干扰是否会产生显著偏差。根据预设的接受标准，确定潜在干扰物质对 Ang I、Ang II、肾素和醛固酮测定的干扰：结果：确定了六种潜在干扰物质对 Ang I 免疫测定的干扰，分别是缬沙坦、硝苯地平、螺内酯、胆固醇、血红蛋白和甘油三酯。同时，乙醇、硝苯地平、螺内酯、肝素钠、华法林、血红蛋白、尿酸、胆固醇和甘油三酯似乎对 Ang II 检测有潜在干扰。葡萄糖、缬沙坦和螺内酯可能对醛固酮免疫测定产生干扰。此外，华法林、缬沙坦、螺内酯、尿酸、胆固醇、未结合胆红素、甘油三酯和血红蛋白也是肾素免疫测定的潜在干扰物质。然而，在醛固酮免疫测定中，这些潜在干扰物质中只有螺内酯超过了预设的平均偏差限（小于±10.0%）：结论：外源性螺内酯会对醛固酮免疫测定产生明显的临床干扰。结论：外源性螺内酯会对醛固酮免疫测定产生明显的临床干扰，而其他物质对血管紧张素Ⅰ、血管紧张素Ⅱ、肾素和醛固酮免疫测定的干扰是可以接受的。

{"title":"Analytical Interference in Chemiluminescence Assay–Measured Angiotensin I, Angiotensin II, Aldosterone, and Renin","authors":"Xiaohua Xu, Yongzhi Xu, Shengqiang Liang","doi":"10.1002/jcla.25045","DOIUrl":"10.1002/jcla.25045","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The interference can be a significant source of laboratory errors with the potential to cause immunoassay results to drift. Therefore, we evaluated the interference in various endogenous and exogenous substances on immunoassay for angiotensin I (Ang I), angiotensin II (Ang II), aldosterone, and renin in vitro.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Ten endogenous and eight exogenous substances were evaluated at supraphysiologic or supratherapeutic plasma levels using the screening study to identify potential interfering substances. Subsequently, potential interfering substances were further tested within maximum pathological or therapeutic plasma concentration ranges using the dose–response study to determine whether the interference has a significant bias. According to preset acceptance criteria, the interference in potential interfering substances for Ang I, Ang II, and renin and aldosterone assays was determined.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Six potential interfering substances for Ang I immunoassays were identified, namely valsartan, nifedipine, spironolactone, cholesterol, hemoglobin, and triglyceride. Meanwhile, ethanol, nifedipine, spironolactone, heparin sodium, warfarin, hemoglobin, uric acid, cholesterol, and triglyceride appeared to have potential interference in the Ang II assay. Three identified as possible interferents for aldosterone immunoassays were glucose, valsartan, and spironolactone. Moreover, warfarin, valsartan, spironolactone, uric acid, cholesterol, bilirubin unconjugated, triglyceride, and hemoglobin were potential interfering substances for renin immunoassays. However, only spironolactone of these potential interfering substances exceeded preset mean bias limits (less than ±10.0%) in aldosterone immunoassays.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Exogenous spironolactone caused clinically significant interference in aldosterone immunoassays. Moreover, the interference in other substances was acceptable in Ang I, Ang II, and renin and aldosterone immunoassays.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15509,"journal":{"name":"Journal of Clinical Laboratory Analysis","volume":"38 10","pages":""},"PeriodicalIF":2.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11211672/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141186672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Effects of Splenectomy on Natural Killer Cell Levels in β-Thalassemia Major Patients 脾切除术对重型β地中海贫血患者自然杀伤细胞水平的影响

IF 2.7 4区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Journal of Clinical Laboratory Analysis

Pub Date : 2024-05-30 DOI: 10.1002/jcla.25046

Ayşegül Uğur Kurtoğlu, Sevcan Uğur, Mesut Göçer, Erdal Kurtoğlu

Aim

In this study, we investigated how splenectomy affects natural killer (NK) cell levels in patients with β-thalassemia major (β-TM).

Materials and Methods

Seventy patients with β-TM (38 splenectomized and 32 nonsplenectomized) and 25 healthy controls were included in this study. The hemogram parameters, ferritin, T lymphocyte, T-helper cell, T-suppressor cell, and NK cell numbers, were measured.

Results

The T lymphocyte (CD3⁺) level was found to be significantly higher in the patient group (p < 0.05). CD3⁺/CD4⁺ T lymphocytes were detected to be significantly higher in the patient group (p < 0.05). Although the CD3⁺/CD4⁺ T lymphocyte level was significantly higher in the nonsplenectomy group (p < 0.05), this was not the case in the splenectomy group. When the patient and control groups were compared, no significant difference was detected regarding CD3⁺/CD8⁺ T lymphocyte levels. CD3⁻/CD16⁺CD56⁺ NK cell level was found to be significantly lower only in the splenectomy group than in the control group (p < 0.05). We found that there was a significant negative correlation between serum ferritin levels and both total lymphocyte (r = −0.617) and CD3⁺ lymphocyte (r = −0.718) levels in the control group (p < 0.05). A significant negative correlation was detected between serum ferritin levels and CD3⁻/CD16⁺CD56⁺ NK cell levels in the patient group (r = −0.410) (p < 0.05).

Conclusion

Splenectomy reduces NK cell levels in patients with β-TM. The negative relationship between ferritin levels and NK cells indicates that ferritin levels should be kept under control in patients with β-TM.

目的：本研究探讨了脾切除术如何影响重型β地中海贫血（β-TM）患者的自然杀伤（NK）细胞水平：研究对象包括 70 名重型地中海贫血患者（38 名脾切除患者和 32 名非脾切除患者）和 25 名健康对照者。研究人员测量了血象参数、铁蛋白、T淋巴细胞、T辅助细胞、T抑制细胞和NK细胞的数量：发现患者组的 T 淋巴细胞（CD3+）水平明显高于非脾切除组（p +/CD4+ T 淋巴细胞水平明显高于非脾切除组（p +/CD8+ T 淋巴细胞水平。发现只有脾切除组的 CD3-/CD16+CD56+ NK 细胞水平明显低于对照组（对照组的 p + 淋巴细胞水平（r = -0.718），患者组的 p -/CD16+CD56+ NK 细胞水平（r = -0.410）（p 结论：脾切除会降低 NK 细胞水平：脾切除可降低β-TM患者的NK细胞水平。铁蛋白水平与 NK 细胞之间的负相关表明，β-TM 患者应控制铁蛋白水平。

{"title":"Effects of Splenectomy on Natural Killer Cell Levels in β-Thalassemia Major Patients","authors":"Ayşegül Uğur Kurtoğlu, Sevcan Uğur, Mesut Göçer, Erdal Kurtoğlu","doi":"10.1002/jcla.25046","DOIUrl":"10.1002/jcla.25046","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>In this study, we investigated how splenectomy affects natural killer (NK) cell levels in patients with β-thalassemia major (β-TM).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>Seventy patients with β-TM (38 splenectomized and 32 nonsplenectomized) and 25 healthy controls were included in this study. The hemogram parameters, ferritin, T lymphocyte, T-helper cell, T-suppressor cell, and NK cell numbers, were measured.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The T lymphocyte (CD3<sup>+</sup>) level was found to be significantly higher in the patient group (<i>p</i> < 0.05). CD3<sup>+</sup>/CD4<sup>+</sup> T lymphocytes were detected to be significantly higher in the patient group (<i>p</i> < 0.05). Although the CD3<sup>+</sup>/CD4<sup>+</sup> T lymphocyte level was significantly higher in the nonsplenectomy group (<i>p</i> < 0.05), this was not the case in the splenectomy group. When the patient and control groups were compared, no significant difference was detected regarding CD3<sup>+</sup>/CD8<sup>+</sup> T lymphocyte levels. CD3<sup>−</sup>/CD16<sup>+</sup>CD56<sup>+</sup> NK cell level was found to be significantly lower only in the splenectomy group than in the control group (<i>p</i> < 0.05). We found that there was a significant negative correlation between serum ferritin levels and both total lymphocyte (<i>r</i> = −0.617) and CD3<sup>+</sup> lymphocyte (<i>r</i> = −0.718) levels in the control group (<i>p</i> < 0.05). A significant negative correlation was detected between serum ferritin levels and CD3<sup>−</sup>/CD16<sup>+</sup>CD56<sup>+</sup> NK cell levels in the patient group (<i>r</i> = −0.410) (<i>p</i> < 0.05).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Splenectomy reduces NK cell levels in patients with β-TM. The negative relationship between ferritin levels and NK cells indicates that ferritin levels should be kept under control in patients with β-TM.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15509,"journal":{"name":"Journal of Clinical Laboratory Analysis","volume":"38 9","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11137841/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141174210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Evaluation of the QMAC-dRAST System Version 2.5 for Rapid Antimicrobial Susceptibility Testing of Gram-Negative Bacteria From Positive Blood Culture Broth and Subcultured Colony Isolates 评估 QMAC-dRAST 系统 2.5 版对阳性血培养肉汤和菌落分离培养物中革兰氏阴性菌的快速抗菌药敏感性测试。

IF 2.7 4区医学 Q2 MEDICAL LABORATORY TECHNOLOGY

Journal of Clinical Laboratory Analysis

Pub Date : 2024-05-28 DOI: 10.1002/jcla.25043

Tae Yeul Kim, Minhee Kang, Hyang Jin Shim, On-Kyun Kang, Hee Jae Huh, Nam Yong Lee

Background

Rapid antimicrobial susceptibility testing (AST) for bloodstream infections (BSIs) facilitates the optimization of antimicrobial therapy, preventing antimicrobial resistance and improving patient outcomes. QMAC-dRAST (QuantaMatrix Inc., Korea) is a rapid AST platform based on microfluidic chip technology that performs AST directly using positive blood culture broth (PBCB). This study evaluated the performance of QMAC-dRAST for Gram-negative bacteria using PBCB and subcultured colony isolates, comparing it with that of VITEK 2 (bioMérieux, France) using broth microdilution (BMD) as the reference method.

Methods

We included 141 Gram-negative blood culture isolates from patients with BSI and 12 carbapenemase-producing clinical isolates of Enterobacterales spiked into blood culture bottles. QMAC-dRAST performance was evaluated using PBCB and colony isolates, whereas VITEK 2 and BMD were tested only on colony isolates.

Results

For PBCB, QMAC-dRAST achieved 92.1% categorical agreement (CA), 95.3% essential agreement (EA), with 1.8% very major errors (VMEs), 3.5% major errors (MEs), and 5.2% minor errors (mEs). With colony isolates, it exhibited 92.5% CA and 95.1% EA, with 2.0% VMEs, 3.2% MEs, and 4.8% mEs. VITEK 2 showed 94.1% CA and 96.0% EA, with 4.3% VMEs, 0.4% MEs, and 4.3% mEs. QMAC-dRAST yielded elevated error rates for specific antimicrobial agents, with high VMEs for carbapenems and aminoglycosides. The median time to result for QMAC-dRAST was 5.9 h for PBCB samples and 6.1 h for subcultured colony isolates.

Conclusions

The QMAC-dRAST system demonstrated considerable strengths and comparable performance to the VITEK 2 system; however, challenges were discerned with specific antimicrobial agents, underlining a necessity for improvement.

背景：针对血流感染（BSI）的快速抗菌药物药敏试验（AST）有助于优化抗菌药物治疗、预防抗菌药物耐药性并改善患者预后。QMAC-dRAST（韩国 QuantaMatrix 公司）是一种基于微流控芯片技术的快速 AST 平台，可直接使用阳性血培养肉汤（PBCB）进行 AST 检测。本研究评估了 QMAC-dRAST 使用 PBCB 和亚培养菌落分离物检测革兰氏阴性菌的性能，并将其与使用肉汤微稀释（BMD）作为参考方法的 VITEK 2（法国生物梅里埃公司）进行了比较：我们从 BSI 患者中采集了 141 份革兰氏阴性血培养分离物，并在血培养瓶中添加了 12 份产碳青霉烯酶的肠杆菌临床分离物。使用 PBCB 和菌落分离物对 QMAC-dRAST 的性能进行了评估，而 VITEK 2 和 BMD 仅对菌落分离物进行了测试：对于 PBCB，QMAC-dRAST 实现了 92.1% 的分类一致 (CA)、95.3% 的基本一致 (EA)、1.8% 的非常大误差 (VME)、3.5% 的大误差 (ME) 和 5.2% 的小误差 (mE)。对于菌落分离物，它显示出 92.5% 的 CA 和 95.1% 的 EA，其中 VME 占 2.0%，ME 占 3.2%，mE 占 4.8%。VITEK 2 的 CA 和 EA 分别为 94.1%和 96.0%，VMEs 为 4.3%，MEs 为 0.4%，mEs 为 4.3%。QMAC-dRAST 对特定抗菌药的错误率较高，碳青霉烯类和氨基糖苷类的 VME 较高。QMAC-dRAST检测PBCB样本的中位结果时间为5.9小时，亚培养菌落分离物的中位结果时间为6.1小时：结论：QMAC-dRAST 系统显示出相当大的优势，其性能可与 VITEK 2 系统媲美；但是，在特定抗菌剂方面存在挑战，因此有必要加以改进。

{"title":"Evaluation of the QMAC-dRAST System Version 2.5 for Rapid Antimicrobial Susceptibility Testing of Gram-Negative Bacteria From Positive Blood Culture Broth and Subcultured Colony Isolates","authors":"Tae Yeul Kim, Minhee Kang, Hyang Jin Shim, On-Kyun Kang, Hee Jae Huh, Nam Yong Lee","doi":"10.1002/jcla.25043","DOIUrl":"10.1002/jcla.25043","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Rapid antimicrobial susceptibility testing (AST) for bloodstream infections (BSIs) facilitates the optimization of antimicrobial therapy, preventing antimicrobial resistance and improving patient outcomes. QMAC-dRAST (QuantaMatrix Inc., Korea) is a rapid AST platform based on microfluidic chip technology that performs AST directly using positive blood culture broth (PBCB). This study evaluated the performance of QMAC-dRAST for Gram-negative bacteria using PBCB and subcultured colony isolates, comparing it with that of VITEK 2 (bioMérieux, France) using broth microdilution (BMD) as the reference method.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We included 141 Gram-negative blood culture isolates from patients with BSI and 12 carbapenemase-producing clinical isolates of Enterobacterales spiked into blood culture bottles. QMAC-dRAST performance was evaluated using PBCB and colony isolates, whereas VITEK 2 and BMD were tested only on colony isolates.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>For PBCB, QMAC-dRAST achieved 92.1% categorical agreement (CA), 95.3% essential agreement (EA), with 1.8% very major errors (VMEs), 3.5% major errors (MEs), and 5.2% minor errors (mEs). With colony isolates, it exhibited 92.5% CA and 95.1% EA, with 2.0% VMEs, 3.2% MEs, and 4.8% mEs. VITEK 2 showed 94.1% CA and 96.0% EA, with 4.3% VMEs, 0.4% MEs, and 4.3% mEs. QMAC-dRAST yielded elevated error rates for specific antimicrobial agents, with high VMEs for carbapenems and aminoglycosides. The median time to result for QMAC-dRAST was 5.9 h for PBCB samples and 6.1 h for subcultured colony isolates.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The QMAC-dRAST system demonstrated considerable strengths and comparable performance to the VITEK 2 system; however, challenges were discerned with specific antimicrobial agents, underlining a necessity for improvement.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15509,"journal":{"name":"Journal of Clinical Laboratory Analysis","volume":"38 9","pages":""},"PeriodicalIF":2.7,"publicationDate":"2024-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11137843/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141158335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0