Pub Date : 2023-01-01DOI: 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.
{"title":"Immunological profile in a pediatric population of patients with spherocytosis. A single-center experience","authors":"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","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}
Pub Date : 2023-01-01DOI: 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.
{"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 , Francesca Carubbi , Maja Di Rocco , Fiorina Giona , 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 < 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).</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}
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+CD45RA−CCR7−HALDR+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.
{"title":"Characterization of peripheral T helper 17 (Th17) cells phenotype in postmenopausal women with estrogen insufficiency","authors":"Hetal Bhadricha , Vainav Patel , Anushree Patil , Suchitra Surve , 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}
Pub Date : 2023-01-01DOI: 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.
{"title":"Rheumatological manifestations of chronic graft versus host disease - Case series","authors":"Jarosław Sabela , Jakub Wroński , Ewa Karakulska-Prystupiuk , Grzegorz Basak , Małgorzata Stasiek , 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}
Pub Date : 2023-01-01DOI: 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.
{"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 , 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","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}
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.
{"title":"Platelet-derived microvesicles activate human platelets via intracellular calcium mediated reactive oxygen species release","authors":"Pooja Yadav , Samir Kumar Beura , Abhishek Ramachandra Panigrahi , Taniya Bhardwaj , Rajanish Giri , 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}
Pub Date : 2023-01-01DOI: 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.
{"title":"Plasma exosomal microRNA expression profiles in patients with high-altitude polycythemia","authors":"Shengyan Wang , Jie Ma , Huiping Qiu , Shizhen Liu , Shouli Zhang , Huihui Liu , Peili Zhang , Ri-li Ge , Guojie Li , 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}
Pub Date : 2023-01-01DOI: 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.
{"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 , 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","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}
Pub Date : 2023-01-01DOI: 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.
{"title":"Ultraviolet light oxidation of fresh hemoglobin eliminates aggregate formation seen in commercially sourced hemoglobin","authors":"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","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}
Pub Date : 2023-01-01DOI: 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.
{"title":"Molecular mechanisms underlying the role of HLA-DQ in systemic immune activation in severe aplastic anemia","authors":"Yuanyuan Shao , Bingnan Liu , Li He , Chunyan Liu, 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}