首页 > 最新文献

Blood Cells Molecules and Diseases最新文献

英文 中文
Immunological profile in a pediatric population of patients with spherocytosis. A single-center experience 球形细胞增多症患儿的免疫学特征。单中心体验
IF 2.3 4区 医学 Q3 HEMATOLOGY Pub Date : 2023-01-01 DOI: 10.1016/j.bcmd.2022.102700
Silvio Marchesani , Letizia Sabatini , Valentina Bertaina , Olivia Marini , Michela Ambrosi , Margherita Di Mauro , Matilde Cossutta , Livia Schettini , Mariachiara Lodi , Gioacchino Andrea Rotulo , Paolo Palma , Giuseppe Palumbo , Giulia Ceglie

Spherocytosis is a hereditary disease caused by the deficiencies of different membrane proteins of red blood cells. Currently, splenectomy is the main therapeutic strategy available, although it is accompanied by an increased risk of sepsis. Several evidences have supported the hypothesis of spleen dysfunction in patients with spherocytosis that haven't yet undergone splenectomy. The aim of this study is to furtherly characterize this aspect, by describing the immune subpopulations in peripheral blood samples obtained from 41 pediatric patients with hereditary spherocytosis by flow cytometry, in order to evaluate changes in the composition of the immune populations compared to 16 healthy donors. Patients were divided in two groups: splenectomized and non-splenectomized. In the splenectomized population, data showed neutrophilic leukocytosis, thrombocytosis, increase in NK and reduction in CD4+ lymphocytes. However, we observed that most of the results obtained in the splenectomized group were found in the non-splenectomized patients as well (increase in neutrophils, in NK, reduction of CD19+, CD4+ lymphocytes and CD4+ and CD8+ naïve cells). The alterations of the immune system may be mainly due to the disease itself, regardless of splenectomy. Therefore, immunological criteria could be included in clinical phenotype assessment in order to better optimize the timing for splenectomy.

球细胞增多症是由红细胞不同膜蛋白缺乏引起的遗传性疾病。目前,脾切除术是可用的主要治疗策略,尽管它会增加败血症的风险。一些证据支持尚未接受脾切除的球形细胞增多症患者脾脏功能障碍的假设。本研究的目的是通过流式细胞术描述41名遗传性球细胞增多症儿童患者外周血样本中的免疫亚群,进一步描述这一方面,以评估与16名健康供体相比免疫群体组成的变化。患者分为两组:脾切除组和非脾切除组。在脾切除人群中,数据显示中性白细胞增多、血小板增多、NK细胞增加和CD4+淋巴细胞减少。然而,我们观察到,在脾切除组中获得的大多数结果也在非脾切除患者中发现(中性粒细胞、NK细胞增加,CD19+、CD4+淋巴细胞以及CD4+和CD8+幼稚细胞减少)。免疫系统的改变可能主要是由于疾病本身,而与脾切除无关。因此,免疫学标准可以纳入临床表型评估,以更好地优化脾切除术的时机。
{"title":"Immunological profile in a pediatric population of patients with spherocytosis. A single-center experience","authors":"Silvio Marchesani ,&nbsp;Letizia Sabatini ,&nbsp;Valentina Bertaina ,&nbsp;Olivia Marini ,&nbsp;Michela Ambrosi ,&nbsp;Margherita Di Mauro ,&nbsp;Matilde Cossutta ,&nbsp;Livia Schettini ,&nbsp;Mariachiara Lodi ,&nbsp;Gioacchino Andrea Rotulo ,&nbsp;Paolo Palma ,&nbsp;Giuseppe Palumbo ,&nbsp;Giulia Ceglie","doi":"10.1016/j.bcmd.2022.102700","DOIUrl":"10.1016/j.bcmd.2022.102700","url":null,"abstract":"<div><p><span><span><span>Spherocytosis is a hereditary disease caused by the deficiencies of different </span>membrane proteins of </span>red blood cells<span>. Currently, splenectomy is the main therapeutic strategy available, although it is accompanied by an increased risk of sepsis. Several evidences have supported the hypothesis of spleen dysfunction </span></span>in patients<span><span> with spherocytosis that haven't yet undergone splenectomy. The aim of this study is to furtherly characterize this aspect, by describing the immune subpopulations in peripheral blood samples obtained from 41 pediatric patients with hereditary spherocytosis by flow cytometry, in order to evaluate changes in the composition of the immune populations compared to 16 healthy donors. Patients were divided in two groups: splenectomized and non-splenectomized. In the splenectomized population, data showed neutrophilic leukocytosis, </span>thrombocytosis<span>, increase in NK and reduction in CD4+ lymphocytes. However, we observed that most of the results obtained in the splenectomized group were found in the non-splenectomized patients as well (increase in neutrophils, in NK, reduction of CD19+, CD4+ lymphocytes and CD4+ and CD8+ naïve cells). The alterations of the immune system may be mainly due to the disease itself, regardless of splenectomy. Therefore, immunological criteria could be included in clinical phenotype assessment in order to better optimize the timing for splenectomy.</span></span></p></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"98 ","pages":"Article 102700"},"PeriodicalIF":2.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40344747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Long-term bone outcomes in Italian patients with Gaucher disease type 1 or type 3 treated with imiglucerase: A sub-study from the International Collaborative Gaucher Group (ICGG) Gaucher Registry 意大利高谢病1型或3型患者接受imiglucerase治疗的长期骨预后:来自国际合作高谢组(ICGG)高谢注册中心的一项亚研究
IF 2.3 4区 医学 Q3 HEMATOLOGY Pub Date : 2023-01-01 DOI: 10.1016/j.bcmd.2022.102705
Maria Domenica Cappellini , Francesca Carubbi , Maja Di Rocco , Fiorina Giona , Gaetano Giuffrida

Background

Gaucher disease (GD) is a lysosomal storage disorder. We evaluated the “real-world” effectiveness of first-line imiglucerase on long-term bone outcomes in Italian patients in the International Collaborative Gaucher Group (ICGG) Gaucher Registry.

Methods

Patients treated with imiglucerase for ≥2 years and with bone assessments at baseline and during follow-up were selected. Data on bone pain, bone crises, marrow infiltration, avascular necrosis, infarction, lytic lesions, Erlenmeyer flask deformity, bone fractures, mineral density, and imiglucerase dosage were evaluated.

Results

Data on bone manifestations were available for 73 of 229 patients (31.9 %). Bone crises frequency decreased significantly from baseline to the most recent follow-up (p < 0.001), with some improvement observed in bone pain prevalence. Bone pain and bone crises prevalence decreased significantly from baseline at 2 to <4 and 4 to <6 years (all p < 0.05). A low median (25th, 75th percentile) baseline imiglucerase dosage was identified in patients reporting bone pain or bone crises (15.0 [13.7, 30.0] and 22.8 [17.5, 36.0] U/kg once every 2 weeks, respectively).

Conclusion

Our study suggests that the management of GD in Italy, with regards to imiglucerase dosage, is suboptimal and confirms the need for clinicians to monitor and correctly treat bone disease according to best practice guidelines.

背景戈谢病(GD)是一种溶酶体储存障碍。我们在国际合作戈谢集团(ICGG)戈谢注册中心评估了一线吡喃葡萄糖酶对意大利患者长期骨疗效的“真实世界”有效性。方法选择接受吡喃葡萄糖治疗≥2年并在基线和随访期间进行骨评估的患者。评估了骨痛、骨危象、骨髓浸润、缺血性坏死、梗死、溶解性病变、锥形烧瓶畸形、骨折、矿物密度和亚氨基葡萄糖酶剂量的数据。结果229例患者中有73例(31.9%)有骨表现数据。从基线到最近的随访,骨危象发生率显著降低(p<0.001),骨痛发生率有所改善。骨痛和骨危象发生率从基线2显著降低到<;4和4到<;6年(均p<0.05)。在报告骨痛或骨危象的患者中,发现了较低的中位(第25,75百分位)基线吡喃激酶剂量(分别为15.0[13.7,3.0]和22.8[17.5,36.0]U/kg,每2周一次),是次优的,并证实临床医生需要根据最佳实践指南监测和正确治疗骨病。
{"title":"Long-term bone outcomes in Italian patients with Gaucher disease type 1 or type 3 treated with imiglucerase: A sub-study from the International Collaborative Gaucher Group (ICGG) Gaucher Registry","authors":"Maria Domenica Cappellini ,&nbsp;Francesca Carubbi ,&nbsp;Maja Di Rocco ,&nbsp;Fiorina Giona ,&nbsp;Gaetano Giuffrida","doi":"10.1016/j.bcmd.2022.102705","DOIUrl":"10.1016/j.bcmd.2022.102705","url":null,"abstract":"<div><h3>Background</h3><p>Gaucher disease (GD) is a lysosomal storage disorder. We evaluated the “real-world” effectiveness of first-line imiglucerase on long-term bone outcomes in Italian patients in the International Collaborative Gaucher Group (ICGG) Gaucher Registry.</p></div><div><h3>Methods</h3><p>Patients treated with imiglucerase for ≥2 years and with bone assessments at baseline and during follow-up were selected. Data on bone pain, bone crises, marrow infiltration, avascular necrosis, infarction, lytic lesions, Erlenmeyer flask deformity, bone fractures, mineral density, and imiglucerase dosage were evaluated.</p></div><div><h3>Results</h3><p>Data on bone manifestations were available for 73 of 229 patients (31.9 %). Bone crises frequency decreased significantly from baseline to the most recent follow-up (p &lt; 0.001), with some improvement observed in bone pain prevalence. Bone pain and bone crises prevalence decreased significantly from baseline at 2 to &lt;4 and 4 to &lt;6 years (all p &lt; 0.05). A low median (25th, 75th percentile) baseline imiglucerase dosage was identified in patients reporting bone pain or bone crises (15.0 [13.7, 30.0] and 22.8 [17.5, 36.0] U/kg once every 2 weeks, respectively).</p></div><div><h3>Conclusion</h3><p>Our study suggests that the management of GD in Italy, with regards to imiglucerase dosage, is suboptimal and confirms the need for clinicians to monitor and correctly treat bone disease according to best practice guidelines.</p></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"98 ","pages":"Article 102705"},"PeriodicalIF":2.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40442260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Characterization of peripheral T helper 17 (Th17) cells phenotype in postmenopausal women with estrogen insufficiency 绝经后雌激素不足妇女外周血T辅助17 (Th17)细胞表型的表征
IF 2.3 4区 医学 Q3 HEMATOLOGY Pub Date : 2023-01-01 DOI: 10.1016/j.bcmd.2022.102702
Hetal Bhadricha , Vainav Patel , Anushree Patil , Suchitra Surve , Meena Desai

Over the past few years, Th17 cells is considered a key player in osteoporosis pathogenesis. Although extensively studied in murine models, comprehensive Th17 cell characterization in osteoporotic women is elusive. We thus aimed to examine peripheral Th17 cells frequency and phenotypes in healthy and osteoporotic women. Our results demonstrated that Th17 cells were primarily CD4+CD45RACCR7HALDR+CCR6lowT-cells. Compared to Pre-N, Post-L showed increased proportion of Th17 with concomitant decrease in Th1 cells. The Th17 cells frequency in effector memory CD4+ T cells was significantly elevated in Post-N with a decrease of Th1 cells in effector memory subsets compared to Pre-N and Post-L. Both Post-N and Post-L had decreased frequency of dual positive Th1-Th17 cells and increased HLA-DR expression on Th17 cells compared to Pre-N. Thus, our study demonstrates increased Th17 cells frequency and reduced Th1 cells frequency with effector memory phenotype in postmenopausal women with estrogen insufficiency and correlates with aging process.

在过去的几年里,Th17细胞被认为是骨质疏松症发病机制的关键因素。尽管在小鼠模型中进行了广泛的研究,但骨质疏松妇女Th17细胞的全面特征尚不明确。因此,我们旨在检测健康和骨质疏松妇女的外周Th17细胞频率和表型。我们的结果表明,Th17细胞主要是CD4+CD45RA−CCR7−HALDR+CR6lowT细胞。与前-N相比,后-L显示Th17比例增加,同时Th1细胞减少。与前-N和后-L相比,效应记忆CD4+T细胞中的Th17细胞频率在后-N中显著升高,而效应记忆亚群中的Th1细胞减少。与前N相比,后N和后L均降低了双阳性Th1-Th17细胞的频率,并增加了Th17细胞上HLA-DR的表达。因此,我们的研究表明,在雌激素不足的绝经后妇女中,Th17细胞频率增加,Th1细胞频率降低,具有效应记忆表型,并与衰老过程相关。
{"title":"Characterization of peripheral T helper 17 (Th17) cells phenotype in postmenopausal women with estrogen insufficiency","authors":"Hetal Bhadricha ,&nbsp;Vainav Patel ,&nbsp;Anushree Patil ,&nbsp;Suchitra Surve ,&nbsp;Meena Desai","doi":"10.1016/j.bcmd.2022.102702","DOIUrl":"10.1016/j.bcmd.2022.102702","url":null,"abstract":"<div><p><span>Over the past few years, Th17 cells<span> is considered a key player in osteoporosis pathogenesis. Although extensively studied in murine models, comprehensive Th17 cell characterization in osteoporotic women is elusive. We thus aimed to examine peripheral Th17 cells frequency and phenotypes in healthy and osteoporotic women. Our results demonstrated that Th17 cells were primarily CD4</span></span><sup>+</sup>CD45RA<sup>−</sup>CCR7<sup>−</sup>HALDR<sup>+</sup>CCR6<sup>low</sup><span>T-cells. Compared to Pre-N, Post-L showed increased proportion of Th17 with concomitant decrease in Th1 cells. The Th17 cells frequency in effector memory CD4</span><sup>+</sup><span> T cells was significantly elevated in Post-N with a decrease of Th1 cells in effector memory subsets compared to Pre-N and Post-L. Both Post-N and Post-L had decreased frequency of dual positive Th1-Th17 cells and increased HLA-DR expression on Th17 cells compared to Pre-N. Thus, our study demonstrates increased Th17 cells frequency and reduced Th1 cells frequency with effector memory phenotype in postmenopausal women with estrogen insufficiency and correlates with aging process.</span></p></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"98 ","pages":"Article 102702"},"PeriodicalIF":2.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40651529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Rheumatological manifestations of chronic graft versus host disease - Case series 慢性移植物抗宿主病的风湿病表现-病例系列
IF 2.3 4区 医学 Q3 HEMATOLOGY Pub Date : 2023-01-01 DOI: 10.1016/j.bcmd.2022.102709
Jarosław Sabela , Jakub Wroński , Ewa Karakulska-Prystupiuk , Grzegorz Basak , Małgorzata Stasiek , Agnieszka Zielińska

Objectives

To present the rheumatological manifestations of chronic graft versus host disease (cGVHD) and describe how they differ from primary systemic connective tissue diseases.

Methods

Description of 7 patients with cGVHD with symptoms resembling Sjögren's syndrome and scleroderma, with a critical review of the literature.

Results

7 patients treated at the hematology department, who developed cGVHD with present antinuclear antibodies, were referred to the rheumatology department for further evaluation. All patients presented symptoms of dry eye syndrome confirmed with ophthalmic tests. If the diagnosis of GVHD was not an exclusion criterion, Sjögren's syndrome criteria would be met by 4 of our patients – they presented not only with dryness but also with typical antibodies, inflammatory changes in salivary glands on ultrasound examination, and mononuclear cell infiltration in histopathological examination of labial salivary glands. Additionally, three patients presented with scleroderma-like syndromes, but with symptoms easy to differentiate from systemic sclerosis.

Conclusion

cGVHD may be difficult to distinguish from Sjögren's syndrome, but such distinction is important due to the different standards of treatment in cGVHD and primary connective tissue diseases.

目的介绍慢性移植物抗宿主病(cGVHD)的风湿病表现,并描述它们与原发性系统性结缔组织疾病的区别。方法对7例症状类似干燥综合征和硬皮病的cGVHD患者进行描述,并对文献进行批判性回顾。结果7例在血液科接受治疗的患者,出现cGVHD并伴有抗核抗体,被转诊至风湿病科进行进一步评估。所有患者均出现干眼综合征症状,经眼科检查证实。如果GVHD的诊断不是排除标准,我们的4名患者将符合干燥综合征标准——他们不仅表现为干燥,而且表现为典型的抗体、超声检查中唾液腺的炎症变化以及唇唾液腺组织病理学检查中的单核细胞浸润。此外,三名患者表现为硬皮病样综合征,但症状易于与系统性硬化症区分。结论cGVHD可能很难与干燥综合征区分开来,但由于cGVHD和原发性结缔组织疾病的治疗标准不同,这种区分很重要。
{"title":"Rheumatological manifestations of chronic graft versus host disease - Case series","authors":"Jarosław Sabela ,&nbsp;Jakub Wroński ,&nbsp;Ewa Karakulska-Prystupiuk ,&nbsp;Grzegorz Basak ,&nbsp;Małgorzata Stasiek ,&nbsp;Agnieszka Zielińska","doi":"10.1016/j.bcmd.2022.102709","DOIUrl":"10.1016/j.bcmd.2022.102709","url":null,"abstract":"<div><h3>Objectives</h3><p><span>To present the rheumatological manifestations of chronic graft versus host disease (cGVHD) and describe how they differ from primary systemic </span>connective tissue diseases.</p></div><div><h3>Methods</h3><p>Description of 7 patients with cGVHD with symptoms resembling Sjögren's syndrome<span> and scleroderma, with a critical review of the literature.</span></p></div><div><h3>Results</h3><p><span><span>7 patients treated at the hematology department, who developed cGVHD with present </span>antinuclear antibodies<span><span>, were referred to the rheumatology department for further evaluation. All patients presented symptoms of dry eye syndrome confirmed with </span>ophthalmic<span> tests. If the diagnosis of GVHD<span> was not an exclusion criterion, Sjögren's syndrome criteria would be met by 4 of our patients – they presented not only with dryness but also with typical antibodies, inflammatory changes in salivary glands on ultrasound examination, and </span></span></span></span>mononuclear cell<span> infiltration in histopathological examination of labial salivary glands. Additionally, three patients presented with scleroderma-like syndromes, but with symptoms easy to differentiate from systemic sclerosis.</span></p></div><div><h3>Conclusion</h3><p>cGVHD may be difficult to distinguish from Sjögren's syndrome, but such distinction is important due to the different standards of treatment in cGVHD and primary connective tissue diseases.</p></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"98 ","pages":"Article 102709"},"PeriodicalIF":2.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40684358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Plasma immune mediators as laboratorial biomarkers for Sickle Cell Disease patients according to the hydroxyurea therapy and disease severity 血浆免疫介质作为镰状细胞病患者根据羟基脲治疗和疾病严重程度的实验室生物标志物
IF 2.3 4区 医学 Q3 HEMATOLOGY Pub Date : 2023-01-01 DOI: 10.1016/j.bcmd.2022.102703
Sílvia Letícia de Oliveira Toledo , Valéria Sutana Ladeira , Leilismara Sousa Nogueira , Letícia Gonçalves Resende Ferreira , Marina Mendes Oliveira , Cristiane de Oliveira Renó , Hérica Lima dos Santos , Jordana Grazziela Alves Coelho-dos-Reis , Ana Carolina Campi-Azevedo , Andréa Teixeira-Carvalho , Olindo Assis Martins-Filho , Danyelle Romana Alves Rios , Melina Barros-Pinheiro

In the present work, the impact of Sickle Cell Disease (SCD) degrees of severity, as well hydroxyurea treatment on the systemic immunological signatures of patients was evaluated. Based on a high-throughput chemokine, cytokine and growth factor multiplex analysis, it was possible to obtain the systemic immunological profile of patients with SCD (n = 40), treated or not with hydroxyurea, as compared to healthy controls (n = 40). Overall, SCD patients with severe disease displayed increased levels of almost all biomarkers analyzed. Our data demonstrated that CXCL8, CCL3 and CXCL10 were pointed out as universal biomarkers of SCD. The results also indicated that HU-untreated patients with indication of HU-therapy display a more prominent increase on plasma immune mediators in a similar way as those with severe SCD disease. Together, these findings provided a comprehensive landscape of evidence that may have implications for further therapeutic strategies and SCD clinical management.

在本工作中,评估了镰状细胞病(SCD)严重程度以及羟基脲治疗对患者全身免疫特征的影响。基于高通量趋化因子、细胞因子和生长因子多重分析,与健康对照组(n=40)相比,有可能获得接受或不接受羟基脲治疗的SCD患者的全身免疫谱。总体而言,患有严重疾病的SCD患者几乎所有分析的生物标志物水平都有所提高。我们的数据表明CXCL8、CCL3和CXCL10是SCD的通用生物标志物。结果还表明,有HU治疗指征的HU未治疗患者的血浆免疫介质表现出更显著的增加,其方式与严重SCD疾病患者相似。总之,这些发现提供了全面的证据,可能对进一步的治疗策略和SCD临床管理有启示。
{"title":"Plasma immune mediators as laboratorial biomarkers for Sickle Cell Disease patients according to the hydroxyurea therapy and disease severity","authors":"Sílvia Letícia de Oliveira Toledo ,&nbsp;Valéria Sutana Ladeira ,&nbsp;Leilismara Sousa Nogueira ,&nbsp;Letícia Gonçalves Resende Ferreira ,&nbsp;Marina Mendes Oliveira ,&nbsp;Cristiane de Oliveira Renó ,&nbsp;Hérica Lima dos Santos ,&nbsp;Jordana Grazziela Alves Coelho-dos-Reis ,&nbsp;Ana Carolina Campi-Azevedo ,&nbsp;Andréa Teixeira-Carvalho ,&nbsp;Olindo Assis Martins-Filho ,&nbsp;Danyelle Romana Alves Rios ,&nbsp;Melina Barros-Pinheiro","doi":"10.1016/j.bcmd.2022.102703","DOIUrl":"10.1016/j.bcmd.2022.102703","url":null,"abstract":"<div><p><span><span>In the present work, the impact of Sickle Cell Disease (SCD) degrees of severity, as well </span>hydroxyurea<span> treatment<span> on the systemic immunological signatures of patients was evaluated. Based on a high-throughput chemokine, cytokine and growth factor multiplex analysis, it was possible to obtain the systemic immunological profile of patients with SCD (</span></span></span><em>n</em><span><span> = 40), treated or not with hydroxyurea, as compared to healthy controls (n = 40). Overall, SCD patients with severe disease displayed increased levels of almost all biomarkers analyzed. Our data demonstrated that CXCL8, CCL3 and </span>CXCL10 were pointed out as universal biomarkers of SCD. The results also indicated that HU-untreated patients with indication of HU-therapy display a more prominent increase on plasma immune mediators in a similar way as those with severe SCD disease. Together, these findings provided a comprehensive landscape of evidence that may have implications for further therapeutic strategies and SCD clinical management.</span></p></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"98 ","pages":"Article 102703"},"PeriodicalIF":2.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33497654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Platelet-derived microvesicles activate human platelets via intracellular calcium mediated reactive oxygen species release 血小板来源的微泡通过细胞内钙介导的活性氧释放激活人血小板
IF 2.3 4区 医学 Q3 HEMATOLOGY Pub Date : 2023-01-01 DOI: 10.1016/j.bcmd.2022.102701
Pooja Yadav , Samir Kumar Beura , Abhishek Ramachandra Panigrahi , Taniya Bhardwaj , Rajanish Giri , Sunil Kumar Singh

Platelet-derived microvesicles (PMVs) are the most abundant microvesicles in circulation, originating from blood platelets via membrane blebbing. PMVs act as biological cargo carrying key molecules from platelets, including immunomodulatory molecules, growth factors, clotting molecules, and miRNAs that can regulate recipient cellular functions. Formation and release of PMVs play an essential role in the pathophysiology of vascular diseases such as hemostasis, inflammation, and thrombosis. Platelet activation is considered the critical event in thrombosis, and a growing number of evidence suggests that oxidative stress-mediated signaling plays a significant role in platelet activation. Ca2+ is a notable player in the generation of ROS in platelets. Reports have established that microvesicles exhibit dual nature in redox mechanisms as they possess both pro-oxidant and antioxidant machinery. However, the impact of PMVs and their ROS machinery on platelets is still a limited explored area. Here, we have demonstrated that PMVs mediate platelet activation via intracellular ROS generation. PMVs interacted with platelets and induced calcium-mediated intracellular ROS production via NADPH oxidase (NOX), leading to platelet activation. Our findings will open up new insights into the tangible relationship of PMVs with platelets and will further contribute to the therapeutic aspects of PMVs in vascular injury and tissue remodeling.

血小板衍生的微泡(PMV)是循环中最丰富的微泡,通过膜起泡来源于血小板。PMV作为携带血小板关键分子的生物货物,包括免疫调节分子、生长因子、凝血分子和可以调节受体细胞功能的miRNA。PMV的形成和释放在止血、炎症和血栓形成等血管疾病的病理生理学中起着重要作用。血小板活化被认为是血栓形成的关键事件,越来越多的证据表明氧化应激介导的信号传导在血小板活化中起着重要作用。Ca2+是血小板中ROS生成的显著参与者。据报道,微泡在氧化还原机制中表现出双重性质,因为它们同时具有促氧化和抗氧化机制。然而,PMV及其ROS机制对血小板的影响仍然是一个有限的探索领域。在这里,我们已经证明PMV通过细胞内ROS的产生介导血小板活化。PMVs与血小板相互作用,并通过NADPH氧化酶(NOX)诱导钙介导的细胞内ROS产生,导致血小板活化。我们的发现将为PMV与血小板的有形关系开辟新的见解,并将进一步有助于PMV在血管损伤和组织重塑中的治疗方面。
{"title":"Platelet-derived microvesicles activate human platelets via intracellular calcium mediated reactive oxygen species release","authors":"Pooja Yadav ,&nbsp;Samir Kumar Beura ,&nbsp;Abhishek Ramachandra Panigrahi ,&nbsp;Taniya Bhardwaj ,&nbsp;Rajanish Giri ,&nbsp;Sunil Kumar Singh","doi":"10.1016/j.bcmd.2022.102701","DOIUrl":"10.1016/j.bcmd.2022.102701","url":null,"abstract":"<div><p><span>Platelet-derived microvesicles (PMVs) are the most abundant microvesicles in circulation, originating from blood platelets </span><em>via</em><span><span> membrane blebbing<span>. PMVs act as biological cargo carrying key molecules from platelets, including immunomodulatory molecules, growth factors, clotting molecules, and miRNAs<span> that can regulate recipient cellular functions. Formation and release of PMVs play an essential role in the pathophysiology<span> of vascular diseases such as hemostasis, inflammation, and thrombosis. </span></span></span></span>Platelet activation is considered the critical event in thrombosis, and a growing number of evidence suggests that oxidative stress-mediated signaling plays a significant role in platelet activation. Ca</span><sup>2+</sup><span> is a notable player in the generation of ROS in platelets. Reports have established that microvesicles exhibit dual nature in redox mechanisms as they possess both pro-oxidant and antioxidant machinery. However, the impact of PMVs and their ROS machinery on platelets is still a limited explored area. Here, we have demonstrated that PMVs mediate platelet activation </span><em>via</em> intracellular ROS generation. PMVs interacted with platelets and induced calcium-mediated intracellular ROS production <em>via</em><span> NADPH oxidase (NOX), leading to platelet activation. Our findings will open up new insights into the tangible relationship of PMVs with platelets and will further contribute to the therapeutic aspects of PMVs in vascular injury and tissue remodeling.</span></p></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"98 ","pages":"Article 102701"},"PeriodicalIF":2.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40346089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 4
Plasma exosomal microRNA expression profiles in patients with high-altitude polycythemia 高原红细胞增多症患者血浆外泌体microRNA表达谱
IF 2.3 4区 医学 Q3 HEMATOLOGY Pub Date : 2023-01-01 DOI: 10.1016/j.bcmd.2022.102707
Shengyan Wang , Jie Ma , Huiping Qiu , Shizhen Liu , Shouli Zhang , Huihui Liu , Peili Zhang , Ri-li Ge , Guojie Li , Sen Cui

High-altitude polycythemia (HAPC) is a chronic mountain sickness characterized by multiple severe ill-effects. Its pathogenesis is still unclear, and till date, no study has been conducted to investigate the plasma exome profile of Tibetan patients with HAPC. In this study, we aimed to elucidate the pathogenesis of HAPC by determining the microRNA (miRNA) signatures. We compared the plasma exosome miRNA expression profiles of eight patients with HAPC and eight healthy controls using next-generation miRNA sequencing. Further, we extracted and identified plasma exosomes using transmission electron microscopy, nanoparticle tracking analysis, and western blotting. We used quantitative reverse-transcription polymerase chain reaction (qRT-PCR) to validate differentially expressed plasma exosomal miRNAs. Finally, we analyzed the diagnostic values of the differentially expressed miRNAs for HAPC using receiver operating characteristic (ROC) curves. We detected 2007 miRNAs from confirmed plasma exosomes, including 1342 known miRNAs and 665 newly predicted miRNAs. We verified the expression of the top 10 differentially expressed miRNAs via qRT-PCR. Patients with HAPC showed significantly upregulated hsa-miR-122-5p, hsa-miR-423-5p, hsa-miR-4433b-3p, hsa-miR-1291, and hsa-miR-106b-5p expression levels, while hsa-miR-200c-3p expression was downregulated. This study may provide background knowledge for future studies on HAPC studies, which may further facilitate the development of novel therapies against this common disease.

高原红细胞增多症(HAPC)是一种以多种严重不良反应为特征的慢性高山病。其发病机制尚不清楚,迄今为止,尚未有研究调查藏族HAPC患者的血浆外显子组谱。在这项研究中,我们旨在通过测定microRNA (miRNA)特征来阐明HAPC的发病机制。我们使用下一代miRNA测序技术比较了8名HAPC患者和8名健康对照者的血浆外泌体miRNA表达谱。此外,我们使用透射电子显微镜、纳米颗粒跟踪分析和western blotting提取和鉴定血浆外泌体。我们使用定量逆转录聚合酶链反应(qRT-PCR)来验证血浆外泌体差异表达的mirna。最后,我们利用受试者工作特征(ROC)曲线分析了差异表达mirna对HAPC的诊断价值。我们从确认的血浆外泌体中检测到2007种mirna,包括1342种已知的mirna和665种新预测的mirna。我们通过qRT-PCR验证了前10个差异表达mirna的表达。HAPC患者hsa-miR-122-5p、hsa-miR-423-5p、hsa-miR-4433b-3p、hsa-miR-1291、hsa-miR-106b-5p表达水平显著上调,hsa-miR-200c-3p表达水平下调。本研究可为今后HAPC的研究提供背景知识,进一步促进这种常见病的新疗法的开发。
{"title":"Plasma exosomal microRNA expression profiles in patients with high-altitude polycythemia","authors":"Shengyan Wang ,&nbsp;Jie Ma ,&nbsp;Huiping Qiu ,&nbsp;Shizhen Liu ,&nbsp;Shouli Zhang ,&nbsp;Huihui Liu ,&nbsp;Peili Zhang ,&nbsp;Ri-li Ge ,&nbsp;Guojie Li ,&nbsp;Sen Cui","doi":"10.1016/j.bcmd.2022.102707","DOIUrl":"10.1016/j.bcmd.2022.102707","url":null,"abstract":"<div><p><span><span>High-altitude polycythemia (HAPC) is a </span>chronic mountain sickness characterized by multiple severe ill-effects. Its pathogenesis is still unclear, and till date, no study has been conducted to investigate the plasma </span>exome<span><span><span> profile of Tibetan patients with HAPC. In this study, we aimed to elucidate the pathogenesis of HAPC by determining the microRNA<span> (miRNA) signatures. We compared the plasma exosome miRNA expression profiles of eight patients with HAPC and eight healthy controls using next-generation miRNA sequencing. Further, we extracted and identified plasma exosomes using </span></span>transmission electron microscopy<span>, nanoparticle tracking analysis, and </span></span>western blotting<span>. We used quantitative reverse-transcription polymerase chain reaction (qRT-PCR) to validate differentially expressed plasma exosomal miRNAs. Finally, we analyzed the diagnostic values of the differentially expressed miRNAs for HAPC using receiver operating characteristic (ROC) curves. We detected 2007 miRNAs from confirmed plasma exosomes, including 1342 known miRNAs and 665 newly predicted miRNAs. We verified the expression of the top 10 differentially expressed miRNAs via qRT-PCR. Patients with HAPC showed significantly upregulated hsa-miR-122-5p, hsa-miR-423-5p, hsa-miR-4433b-3p, hsa-miR-1291, and hsa-miR-106b-5p expression levels, while hsa-miR-200c-3p expression was downregulated. This study may provide background knowledge for future studies on HAPC studies, which may further facilitate the development of novel therapies against this common disease.</span></span></p></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"98 ","pages":"Article 102707"},"PeriodicalIF":2.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40445796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Influence of initial clinical suspicion on the diagnostic yield of laboratory enzymatic testing in lysosomal storage disorders. Experience from a multispecialty hospital 初步临床怀疑对溶酶体贮积症实验室酶检测诊断率的影响。有多专科医院的工作经验
IF 2.3 4区 医学 Q3 HEMATOLOGY Pub Date : 2023-01-01 DOI: 10.1016/j.bcmd.2022.102704
Clara Carnicer-Cáceres , Yolanda Villena-Ortiz , Laura Castillo-Ribelles , Raquel Barquín-del-Pino , Maria Camprodon-Gomez , Ana Felipe-Rucián , David Moreno-Martínez , Sara Lucas-del-Pozo , Jorge Hernández-Vara , Anna García-Serra , Ariadna Tigri-Santiña , Marc Moltó-Abad , Irene Agraz-Pamplona , Jose F. Rodriguez-Palomares , Javier Limeres-Freire , Marc Macaya-Font , Victor Rodríguez-Sureda , Lucy Dougherty-De Miguel , Mireia del-Toro-Riera , Guillem Pintos-Morell , Jose Antonio Arranz-Amo

Lysosomal storage disorders (LSD) are a group of inherited metabolic diseases mainly caused by a deficiency of lysosomal hydrolases, resulting in a gradual accumulation of non-degraded substrates in different tissues causing the characteristic clinical manifestations of such disorders. Confirmatory tests of suspected LSD individuals include enzymatic and genetic testing. A well-oriented clinical suspicion can improve the cost-effectiveness of confirmatory tests and reduce the time expended to achieve the diagnosis. Thus, this work aims to retrospectively study the influence of clinical orientation on the diagnostic yield of enzymatic tests in LSD by retrieving clinical, biochemical, and genetic data obtained from subjects with suspicion of LSD. Our results suggest that the clinical manifestations at the time of diagnosis and the initial clinical suspicion can have a great impact on the diagnostic yield of enzymatic tests, and that clinical orientation performed in specialized clinical departments can contribute to improve it. In addition, the analysis of enzymatic tests as the first step in the diagnostic algorithm can correctly guide subsequent confirmatory genetic tests, in turn increasing their diagnostic yield. In summary, our results suggest that initial clinical suspicion plays a crucial role on the diagnostic yield of confirmatory enzymatic tests in LSD.

溶酶体储存障碍(LSD)是一组遗传性代谢疾病,主要由溶酶体水解酶缺乏引起,导致未降解的底物在不同组织中逐渐积累,导致此类疾病的特征性临床表现。对疑似LSD个体的验证性测试包括酶测试和基因测试。有针对性的临床怀疑可以提高验证性测试的成本效益,并减少实现诊断所花费的时间。因此,本工作旨在通过检索从疑似LSD受试者获得的临床、生化和遗传数据,回顾性研究临床取向对LSD酶促试验诊断率的影响。我们的结果表明,诊断时的临床表现和最初的临床怀疑会对酶测试的诊断率产生很大影响,在专业临床部门进行临床指导有助于提高诊断率。此外,将酶测试作为诊断算法的第一步进行分析,可以正确地指导后续的验证性基因测试,从而提高其诊断率。总之,我们的研究结果表明,最初的临床怀疑对LSD的确认性酶测试的诊断率起着至关重要的作用。
{"title":"Influence of initial clinical suspicion on the diagnostic yield of laboratory enzymatic testing in lysosomal storage disorders. Experience from a multispecialty hospital","authors":"Clara Carnicer-Cáceres ,&nbsp;Yolanda Villena-Ortiz ,&nbsp;Laura Castillo-Ribelles ,&nbsp;Raquel Barquín-del-Pino ,&nbsp;Maria Camprodon-Gomez ,&nbsp;Ana Felipe-Rucián ,&nbsp;David Moreno-Martínez ,&nbsp;Sara Lucas-del-Pozo ,&nbsp;Jorge Hernández-Vara ,&nbsp;Anna García-Serra ,&nbsp;Ariadna Tigri-Santiña ,&nbsp;Marc Moltó-Abad ,&nbsp;Irene Agraz-Pamplona ,&nbsp;Jose F. Rodriguez-Palomares ,&nbsp;Javier Limeres-Freire ,&nbsp;Marc Macaya-Font ,&nbsp;Victor Rodríguez-Sureda ,&nbsp;Lucy Dougherty-De Miguel ,&nbsp;Mireia del-Toro-Riera ,&nbsp;Guillem Pintos-Morell ,&nbsp;Jose Antonio Arranz-Amo","doi":"10.1016/j.bcmd.2022.102704","DOIUrl":"10.1016/j.bcmd.2022.102704","url":null,"abstract":"<div><p><span><span>Lysosomal storage disorders (LSD) are a group of inherited </span>metabolic diseases mainly caused by a deficiency of lysosomal </span>hydrolases<span>, resulting in a gradual accumulation of non-degraded substrates in different tissues causing the characteristic clinical manifestations of such disorders. Confirmatory tests of suspected LSD individuals include enzymatic and genetic testing. A well-oriented clinical suspicion can improve the cost-effectiveness of confirmatory tests and reduce the time expended to achieve the diagnosis. Thus, this work aims to retrospectively study the influence of clinical orientation on the diagnostic yield of enzymatic tests in LSD by retrieving clinical, biochemical, and genetic data obtained from subjects with suspicion of LSD. Our results suggest that the clinical manifestations at the time of diagnosis and the initial clinical suspicion can have a great impact on the diagnostic yield of enzymatic tests, and that clinical orientation performed in specialized clinical departments can contribute to improve it. In addition, the analysis of enzymatic tests as the first step in the diagnostic algorithm can correctly guide subsequent confirmatory genetic tests, in turn increasing their diagnostic yield. In summary, our results suggest that initial clinical suspicion plays a crucial role on the diagnostic yield of confirmatory enzymatic tests in LSD.</span></p></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"98 ","pages":"Article 102704"},"PeriodicalIF":2.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10477385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Ultraviolet light oxidation of fresh hemoglobin eliminates aggregate formation seen in commercially sourced hemoglobin 紫外线氧化新鲜血红蛋白消除了在商业来源的血红蛋白中所见的聚集形成
IF 2.3 4区 医学 Q3 HEMATOLOGY Pub Date : 2023-01-01 DOI: 10.1016/j.bcmd.2022.102699
Aqeela Afzal , William N. Beavers , Eric P. Skaar , Margaret C. Calhoun , Kelly A. Richardson , Stuart R. Landstreet , David E. Cliffel , David Wright , Julie A. Bastarache , Lorraine B. Ware

Elevated levels of circulating cell-free hemoglobin (CFH) are an integral feature of several clinical conditions including sickle cell anemia, sepsis, hemodialysis and cardiopulmonary bypass. Oxidized (Fe3+, ferric) hemoglobin contributes to the pathophysiology of these disease states and is therefore widely studied in experimental models, many of which use commercially sourced CFH. In this study, we treated human endothelial cells with commercially sourced ferric hemoglobin and observed the appearance of dense cytoplasmic aggregates (CAgg) over time. These CAgg were intensely autofluorescent, altered intracellular structures (such as mitochondria), formed in multiple cell types and with different media composition, and formed regardless of the presence or absence of cells. An in-depth chemical analysis of these CAgg revealed that they contain inorganic components and are not pure hemoglobin. To oxidize freshly isolated hemoglobin without addition of an oxidizing agent, we developed a novel method to convert ferrous CFH to ferric CFH using ultraviolet light without the need for additional redox agents. Unlike commercial ferric hemoglobin, treatment of cells with the fresh ferric hemoglobin did not lead to CAgg formation. These studies suggest that commercially sourced CFH may contain stabilizers and additives which contribute to CAgg formation.

循环无细胞血红蛋白(CFH)水平升高是镰状细胞贫血、败血症、血液透析和体外循环等多种临床疾病的一个重要特征。氧化(Fe3+,三价铁)血红蛋白有助于这些疾病状态的病理生理学,因此在实验模型中被广泛研究,其中许多模型使用商业来源的CFH。在这项研究中,我们用商业来源的铁血红蛋白处理人类内皮细胞,并随着时间的推移观察到致密细胞质聚集体(CAgg)的出现。这些CAgg是强烈的自发荧光,改变了细胞内结构(如线粒体),在多种细胞类型和不同的培养基组成中形成,并且无论是否存在细胞都会形成。对这些CAgg的深入化学分析表明,它们含有无机成分,不是纯血红蛋白。为了在不添加氧化剂的情况下氧化新分离的血红蛋白,我们开发了一种新的方法,使用紫外线将亚铁CFH转化为铁CFH,而不需要额外的氧化还原剂。和商业铁血红蛋白不同,用新鲜铁血红蛋白处理细胞并没有导致CAgg的形成。这些研究表明,商业来源的CFH可能含有有助于CAgg形成的稳定剂和添加剂。
{"title":"Ultraviolet light oxidation of fresh hemoglobin eliminates aggregate formation seen in commercially sourced hemoglobin","authors":"Aqeela Afzal ,&nbsp;William N. Beavers ,&nbsp;Eric P. Skaar ,&nbsp;Margaret C. Calhoun ,&nbsp;Kelly A. Richardson ,&nbsp;Stuart R. Landstreet ,&nbsp;David E. Cliffel ,&nbsp;David Wright ,&nbsp;Julie A. Bastarache ,&nbsp;Lorraine B. Ware","doi":"10.1016/j.bcmd.2022.102699","DOIUrl":"10.1016/j.bcmd.2022.102699","url":null,"abstract":"<div><p><span>Elevated levels of circulating cell-free hemoglobin (CFH) are an integral feature of several clinical conditions including sickle cell anemia<span><span>, sepsis, hemodialysis and </span>cardiopulmonary bypass. Oxidized (Fe</span></span><sup>3+</sup><span><span>, ferric) hemoglobin contributes to the pathophysiology<span> of these disease states and is therefore widely studied in experimental models, many of which use commercially sourced CFH. In this study, we treated human endothelial cells with commercially sourced </span></span>ferric hemoglobin<span> and observed the appearance of dense cytoplasmic aggregates (CAgg) over time. These CAgg were intensely autofluorescent, altered intracellular structures (such as mitochondria), formed in multiple cell types and with different media composition, and formed regardless of the presence or absence of cells. An in-depth chemical analysis of these CAgg revealed that they contain inorganic components and are not pure hemoglobin. To oxidize freshly isolated hemoglobin without addition of an oxidizing agent<span>, we developed a novel method to convert ferrous CFH to ferric CFH using ultraviolet light without the need for additional redox agents. Unlike commercial ferric hemoglobin, treatment of cells with the fresh ferric hemoglobin did not lead to CAgg formation. These studies suggest that commercially sourced CFH may contain stabilizers and additives which contribute to CAgg formation.</span></span></span></p></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"98 ","pages":"Article 102699"},"PeriodicalIF":2.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10024311/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9222117","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
Molecular mechanisms underlying the role of HLA-DQ in systemic immune activation in severe aplastic anemia HLA-DQ在严重再生障碍性贫血的全身免疫激活中的作用的分子机制
IF 2.3 4区 医学 Q3 HEMATOLOGY Pub Date : 2023-01-01 DOI: 10.1016/j.bcmd.2022.102708
Yuanyuan Shao , Bingnan Liu , Li He , Chunyan Liu, Rong Fu

Severe aplastic anemia (SAA) is a bone marrow failure disorder caused by autoimmune dysfunction. The presentation by dendritic cells (DCs) is the key step in initiating the immune response against unknown antigens in SAA patients. In the previous phase, we found that compared to healthy controls, patients with SAA had an increased proportion of circulating myeloid/conventional dendritic cells (mDCs/cDCs) with enhanced phagocytosis, more secretion of Th1-type cytokines (IL-2, TNF-α, IFN-γ) in the bone marrow, and a reduced proportion of Treg cells. In this study, we found that cDCs sorted from SAA patients had higher expression level of HLA-DQ, co-stimulatory molecules CD86, PTK and ERK1/2 than the remission SAA patients and healthy controls. Moreover, downregulation of HLA-DQ protein levels on cDCs derived from SAA patients resulted in reduced phagocytosis rate and CD86 expression of cDCs. When the cDCs above were co-cultured with CD4+ cells from the same patients, reduced secretion of Th1 type of lymphocyte cytokines was observed. Analysis of clinically relevant data suggests that HLA-DQ expression levels were closely related to disease severity and immune status of patients. These findings show that the role of HLA-DQ in the immunopathogenesis of SAA is potentially important and worth further study.

严重再生障碍性贫血(SAA)是一种由自身免疫功能障碍引起的骨髓衰竭性疾病。树突状细胞(DC)的呈递是SAA患者启动针对未知抗原的免疫反应的关键步骤。在前一阶段,我们发现与健康对照组相比,SAA患者的循环髓系/常规树突状细胞(mDCs/cDCs)比例增加,吞噬功能增强,骨髓中Th1型细胞因子(IL-2、TNF-α、IFN-γ)分泌增多,Treg细胞比例降低。在本研究中,我们发现从SAA患者中分离的cDC的HLA-DQ、共刺激分子CD86、PTK和ERK1/2的表达水平高于缓解期SAA患者和健康对照。此外,SAA患者来源的cDC上HLA-DQ蛋白水平的下调导致cDC的吞噬率和CD86表达降低。当上述cDC与来自相同患者的CD4+细胞共培养时,观察到Th1型淋巴细胞细胞因子的分泌减少。临床相关数据分析表明,HLA-DQ的表达水平与疾病的严重程度和患者的免疫状态密切相关。这些发现表明,HLA-DQ在SAA免疫发病中的作用具有潜在的重要意义,值得进一步研究。
{"title":"Molecular mechanisms underlying the role of HLA-DQ in systemic immune activation in severe aplastic anemia","authors":"Yuanyuan Shao ,&nbsp;Bingnan Liu ,&nbsp;Li He ,&nbsp;Chunyan Liu,&nbsp;Rong Fu","doi":"10.1016/j.bcmd.2022.102708","DOIUrl":"10.1016/j.bcmd.2022.102708","url":null,"abstract":"<div><p>Severe aplastic anemia (SAA) is a bone marrow failure disorder caused by autoimmune dysfunction. The presentation by dendritic cells (DCs) is the key step in initiating the immune response against unknown antigens in SAA patients. In the previous phase, we found that compared to healthy controls, patients with SAA had an increased proportion of circulating myeloid/conventional dendritic cells (mDCs/cDCs) with enhanced phagocytosis, more secretion of Th1-type cytokines (IL-2, TNF-α, IFN-γ) in the bone marrow, and a reduced proportion of Treg cells. In this study, we found that cDCs sorted from SAA patients had higher expression level of HLA-DQ, co-stimulatory molecules CD86, PTK and ERK1/2 than the remission SAA patients and healthy controls. Moreover, downregulation of HLA-DQ protein levels on cDCs derived from SAA patients resulted in reduced phagocytosis rate and CD86 expression of cDCs. When the cDCs above were co-cultured with CD4<sup>+</sup> cells from the same patients, reduced secretion of Th1 type of lymphocyte cytokines was observed. Analysis of clinically relevant data suggests that HLA-DQ expression levels were closely related to disease severity and immune status of patients. These findings show that the role of HLA-DQ in the immunopathogenesis of SAA is potentially important and worth further study.</p></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"98 ","pages":"Article 102708"},"PeriodicalIF":2.3,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40445797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
期刊
Blood Cells Molecules and Diseases
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1