Blood Cells Molecules and Diseases最新文献

{"title":"Molecular characterization of a novel 83.9-kb deletion of the α-globin upstream regulatory elements by long-read sequencing","authors":"Jianjiang Feng ,&nbsp;Aiping Mao ,&nbsp;Ye Lu ,&nbsp;Haihong Shi ,&nbsp;Wanli Meng ,&nbsp;Chen Liang","doi":"10.1016/j.bcmd.2023.102764","DOIUrl":"10.1016/j.bcmd.2023.102764","url":null,"abstract":"<div><p><span><span>Inherited deletions of upstream regulatory elements of α-globin genes give rise to α-thalassemia, which is an autosomal recessive<span><span> monogenic disease. However, conventional thalassemia<span> target diagnosis often fails to identify these rare deletions. Here we reported a family with two previous pregnancies of Hb Bart's hydrops fetalis and was seeking for </span></span>prenatal diagnosis during the third pregnancy. Both parents had low level of </span></span>Hemoglobin A2<span> indicating α-thalassemia. Conventional Gap-PCR and PCR-reverse dot blot showed the father carried –</span></span>^SEA deletion but did not identify any variants in the mother. Multiplex ligation-dependent probe amplification identified a deletion containing two HS-40 probes but could not determine the exact region. Finally, a long-read sequencing (LRS)-based approach directly identified that the exact deletion region was chr16: 48,642-132,584, which was located in the α-globin upstream regulatory elements and named (αα)^JM<span> after the Jiangmen city. Gap-PCR and Sanger sequencing confirmed the breakpoint. Both the mother and fetus from the third pregnancy carried heterozygous (αα)</span>^JM, and the fetus was normally delivered at gestational age of 39 weeks. This study demonstrated that LRS technology had great advantages over conventional target diagnosis methods for identifying rare thalassemia variants and assisted better carrier screening and prenatal diagnosis of thalassemia.</p></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2023-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9997888","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}

{"title":"Essential genetic modifiers and their measurable impact in a community-recruited population analysis for non-severe hemoglobin E/β-thalassemia prenatal genetic counseling.","authors":"P. Wong, Thirabhat Chitsobhak, Suporn Jittasathian, Chonnigarn Sirichantharawat, Naritsara Cherdchoo, Weerapong Prangcharoen, Patcharanapa Jongautchariyakul, K. Jampachaisri, Akamon Tapprom, R. Deoisares, Piyatida Chumnumsiriwath","doi":"10.2139/ssrn.4375660","DOIUrl":"https://doi.org/10.2139/ssrn.4375660","url":null,"abstract":"The study aimed to identify essential phenotype-modulating factors among the pre-existence of several important ones and clarify their measurable impact on the clinical severity of hemoglobin (Hb) E/β-thalassemia in a community-recruited population analysis. This prospective study was designed to compare modifiers between community- (less or no symptoms) and hospital-recruited individuals with Hb E/β-thalassemia. The formerly included couples previously assessed for prenatal thalassemia at-risk status at 42 community and 7 referral hospitals in Thailand through on-site investigations between June 2020 and December 2021. The control included Hb E/β-thalassemia patients undergoing transfusions. The Mahidol score classified disease severity. Beta-globin, α0-thalassemia (-SEA, -THAI), α+-thalassemia (-α3.7, -α4.2), Hb Constant Spring (αCS) alleles, rs766432 in BCL11A, rs9399137 in HBS1L-MYB, and rs7482144-XmnI were evaluated. Modifiers were compared between 102 community- and 104 hospital-recruited cases. Alleles of β+, -SEA, -α3.7, αCS, and a minor allele of rs9399137 were prevalent in the community and mild severity groups (p < 0.05). Multiple linear regression analysis associated modulating alleles with -4.299 (-SEA), -3.654 (β+), -3.065 (rs9399137, C/C), -2.888 (αCS), -2.623 (-α3.7), -2.361 (rs7482144, A/A), -1.258 (rs9399137, C/T), and -1.174 (rs7482144, A/G) severity score reductions (p < 0.05). Certain modifiers must be considered in routine prenatal genetic counseling for Hb E/β-thalassemia.","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47990012","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}

{"title":"Cellular and animal models for the investigation of β-thalassemia","authors":"Antonella Nai ,&nbsp;Celia Cordero-Sanchez ,&nbsp;Emanuele Tanzi ,&nbsp;Alessia Pagani ,&nbsp;Laura Silvestri ,&nbsp;Simona Maria Di Modica","doi":"10.1016/j.bcmd.2023.102761","DOIUrl":"10.1016/j.bcmd.2023.102761","url":null,"abstract":"<div><p><span><span><span>β-Thalassemia is a genetic<span> form of anemia due to mutations in the β-globin gene, that leads to ineffective and extramedullary erythropoiesis, abnormal </span></span>red blood cells<span><span> and secondary iron-overload. The severity of the disease ranges from mild to lethal anemia based on the residual levels of globins<span><span><span> production. Despite being a monogenic disorder, the </span>pathophysiology of β-thalassemia is multifactorial, with different players contributing to the severity of anemia and secondary complications. As a result, the identification of effective therapeutic strategies is complex, and the </span>treatment of patients is still suboptimal. For these reasons, several models have been developed in the last decades to provide experimental tools for the study of the disease, including </span></span>erythroid cell lines, cultures of primary erythroid cells and </span></span>transgenic animals<span><span>. Years of research enabled the optimization of these models and led to decipher the mechanisms responsible for globins deregulation and ineffective erythropoiesis<span> in thalassemia, to unravel the role of </span></span>iron homeostasis in the disease and to identify and validate novel therapeutic targets and agents. Examples of successful outcomes of these analyses include iron restricting agents, currently tested in the clinics, several gene therapy vectors, one of which was recently approved for the treatment of most severe patients, and a promising gene editing strategy, that has been shown to be effective in a </span></span>clinical trial. This review provides an overview of the available models, discusses pros and cons, and the key findings obtained from their study.</p></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2023-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9574537","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}

{"title":"Inherited disorders of hemoglobin: A review of old and new diagnostic methods","authors":"Emily Franco ,&nbsp;Kristine A. Karkoska ,&nbsp;Patrick T. McGann","doi":"10.1016/j.bcmd.2023.102758","DOIUrl":"10.1016/j.bcmd.2023.102758","url":null,"abstract":"<div><p><span>The genetic<span> regulation of hemoglobin is complex and there are a number of genetic abnormalities that result in clinically important hemoglobin disorders. Here, we review the molecular pathophysiology<span> of hemoglobin disorders and review both old and new methods of diagnosing these disorders. Timely diagnosis of hemoglobinopathies in infants is essential to coordinate optimal life-saving interventions, and accurate identification of carriers of deleterious mutations allows for </span></span></span>genetic counseling<span><span><span><span><span> and informed family planning. The initial laboratory workup of inherited disorders of hemoglobin should include a complete blood count (CBC) and peripheral </span>blood smear, followed by carefully selected tests based on clinical suspicion and available methodology. We discuss the utility and limitations of the various methodologies to fractionate hemoglobin, including </span>cellulose acetate and citrate agar </span>hemoglobin electrophoresis<span>, isoelectric focusing<span>, high-resolution high-performance liquid chromatography, and capillary zone electrophoresis<span>. Recognizing that most of the global burden of hemoglobin disorders exists in low- and middle-income countries, we review the increasingly available array of point-of-care-tests (POCT), which have an increasingly important role in expanding early diagnosis programs to address the global burden of sickle cell disease, including Sickle SCAN, HemoTypeSC, Gazelle </span></span></span></span>Hb Variant<span>, and Smart LifeLC. A comprehensive understanding of the molecular pathophysiology of hemoglobin and the globin genes<span>, as well as a clear understanding of the utility and limitations of currently available diagnostic tests, is essential in reducing global disease burden.</span></span></span></p></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2023-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9904520","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}

{"title":"Characterization of peripheral blood T follicular helper (TFH) cells in patients with type 1 Gaucher disease and carriers","authors":"Ramazan Uzen ,&nbsp;Fahri Bayram ,&nbsp;Huseyin Dursun ,&nbsp;Fatih Kardas ,&nbsp;Mustafa Cakir ,&nbsp;Nurhan Cucer ,&nbsp;Ahmet Eken ,&nbsp;Hamiyet Donmez-Altuntas","doi":"10.1016/j.bcmd.2023.102728","DOIUrl":"10.1016/j.bcmd.2023.102728","url":null,"abstract":"<div><h3>Background</h3><p>Gaucher disease<span><span><span> (GD) is the most common autosomal recessive </span>lipid storage disease. In this study, the changes in </span>TFH cells and IL-4 and IL-21 cytokines in blood samples of GD patients, carriers and healthy volunteers were investigated.</span></p></div><div><h3>Methods</h3><p>Two pretreatment type 1 GD patients, 20 currently treated type 1 GD patients, 6 carriers, and 27 healthy volunteers were enrolled in the study. TFH cell (CD45RA⁻CD4⁺<span>CXCR5</span>⁺<span>) number, phenotype (PD1, ICOS expression), and cytokine production (IL-21, IL-4) were assessed via flow cytometric assays.</span></p></div><div><h3>Results</h3><p>No significant differences were found between the groups with respect to the number, frequency and PD1 or ICOS expression of TFH cells between healthy controls, patients and carriers. However, IL-4⁺ TFH cells were significantly reduced both in percent and number in the treated GD patients compared with healthy controls (<em>p</em> &lt; 0.05). Interestingly, the IL-21⁺<span> TFH cell number was increased in treated GD patients. When TFH cells were examined based on CXCR3 expression, the frequency of the PD1</span>⁺Th17-Th2-like fraction (CXCR3⁻) was found to be significantly increased in treated GD patients.</p></div><div><h3>Conclusion</h3><p>To our knowledge, this is the first study to assess TFH cells in GD patients, and to show that the production of IL-4 and IL-21 by TFH cells and their subsets may be altered in type 1 GD patients.</p></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9157039","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}

{"title":"γ′ fibrinogen levels as a biomarker of COVID-19 respiratory disease severity","authors":"L. Kornblith, Bindhya Sadhanandhan, Sreepriya Arun, Rebecca Long, Alicia J. Johnson, Jamie Noll, C. N. Ramchand, J. Olynyk, D. Farrell","doi":"10.2139/ssrn.4383116","DOIUrl":"https://doi.org/10.2139/ssrn.4383116","url":null,"abstract":"Coronavirus disease 2019 (COVID-19) is characterized by a pro-inflammatory state associated with organ failure, thrombosis, and death. We investigated a novel inflammatory biomarker, γ′ fibrinogen (GPF), in 103 hospitalized patients with COVID-19 and 19 healthy controls. We found significant associations between GPF levels and the severity of COVID-19 as judged by blood oxygen saturation (SpO2). The mean level of GPF in the patients with COVID-19 was significantly higher than in controls (69.8 (95 % CI 64.8–74.8) mg/dL compared with 36.9 (95 % CI 31.4–42.4) mg/dL, p < 0.0001), whereas C-reactive protein (CRP), lactate dehydrogenase (LDH), and total fibrinogen levels were not significantly different between groups. Mean GPF levels were significantly highest in patients with severe COVID-19 (SpO2 ≤ 93 %, GPF 75.2 (95 % CI 68.7–81.8) mg/dL), compared to mild/moderate COVID-19 (SpO2 > 93 %, GPF 62.5 (95 % CI 55.0–70.0) mg/dL, p = 0.01, AUC of 0.68, 95 % CI 0.57–0.78; Youden's index cutpoint 62.9 mg/dL, sensitivity 0.64, specificity 0.63). In contrast, CRP, interleukin-6, ferritin, LDH, D-dimers, and total fibrinogen had weaker associations with COVID-19 disease severity (all ROC curves with lower AUCs). Thus, GPF may be a useful inflammatory marker of COVID-19 respiratory disease severity.","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2023-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47520561","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}

{"title":"Effects of d-ribose on human erythrocytes: Non-enzymatic glycation of hemoglobin, eryptosis, oxidative stress and energy metabolism","authors":"Zehong Zhang ,&nbsp;Yu Tai ,&nbsp;Zhi Liu ,&nbsp;Yunxia Pu ,&nbsp;Liang An ,&nbsp;Xiaojing Li ,&nbsp;Lili Li ,&nbsp;Yaqi Wang ,&nbsp;Zhongbin Yang ,&nbsp;Chao Duan ,&nbsp;Kun Hou ,&nbsp;Qing Zhang ,&nbsp;Fuyu Ren ,&nbsp;Qiang Ma ,&nbsp;Yan Su","doi":"10.1016/j.bcmd.2023.102725","DOIUrl":"10.1016/j.bcmd.2023.102725","url":null,"abstract":"<div><p><span>d</span><span>-Ribose is not only an important component of some biomacromolecules, but also an active pentose with strong reducibility and non-enzymatic glycation ability. Previous studies reported the diverse role of </span><span>d</span>-ribose in different cells. In this study, the effects of <span>d</span><span><span>-ribose on non-enzymatic glycation of hemoglobin (Hb), as well as eryptosis, </span>oxidative stress<span> and energy metabolism of erythrocytes were observed by molecular fluorescence spectrophotometry, multi-wavelength spectrophotometry, high-pressure liquid chromatography (HPLC), mass spectrometry (MS) and flow cytometer. The results showed that </span></span><span>d</span>-ribose had the strongest non-enzymatic glycation ability to Hb <em>in vitro</em><span> when compared with other monosaccharides, and could enter the erythrocytes in a concentration-dependent manner, which was not inhibited by the specific glucose transporter 1 (GLUT1) inhibitor WZB117. In addition, </span><span>d</span><span>-ribose incubation increased the HbA1c<span>, hemolysis, eryptosis, and ROS level of erythrocytes significantly more than that of </span></span><span>d</span><span>-glucose, however, no changes were observed in the levels of ATP, NADPH, and other intermediate energy metabolites in </span><span>d</span><span>-ribose treatment. Therefore, the strong non-enzymatic glycation ability of </span><span>d</span>-ribose may play an important role in erythrocyte damage.</p></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10724974","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}

{"title":"Daratumumab as a novel treatment option in refractory ITP","authors":"Ilze Vernava ,&nbsp;Clemens A. Schmitt","doi":"10.1016/j.bcmd.2023.102724","DOIUrl":"10.1016/j.bcmd.2023.102724","url":null,"abstract":"<div><p><span><span><span><span>Primary immune thrombocytopenia (ITP) in adult patients typically presents as a repeatedly relapsing disease in need of multiple lines of therapy. Here we report the clinical courses of two patients, an 82-year-old female and a 54-year-old male, with primary ITP after multiple relapses and exhausted standard </span>therapies<span>, which we treated with the myeloma-licensed anti-CD38 monoclonal antibody </span></span>daratumumab in an off-label setting. Daratumumab is known to target preferentially </span>plasmablasts<span><span><span><span><span>, short-lived plasma cells and long-lived plasma cells, with the latter being the major source of antiplatelet autoantibodies. Noteworthy, </span>rituximab, a </span>CD20<span> antibody, targets earlier steps in B-cell ontogenesis, thereby indirectly decreasing plasmablasts and short-lived plasma cells, but to a lesser extent long-lived plasma cells, which tend to persist after rituximab treatment. Several single-patient reports and case series have demonstrated successful treatment with daratumumab in ITP, autoimmune thrombocytopenia in </span></span>Evans syndrome<span> as well as other cytopenias<span><span> or pure red cell aplasia after </span>allogeneic stem cell transplantation<span> or in congenital diseases, systemic lupus erythematodes and cold </span></span></span></span>agglutinin<span> disease. Our first patient with isolated primary ITP rapidly and lastingly responded to daratumumab plus tapered steroids, with platelet counts above 50 × 10</span></span></span>⁹<span>/L within weeks and subsequently even stably within the normal range. Despite no objective response observed in the second patient, a lasting clinical stabilization was achieved. As the underlying mode of action, we hypothesize here daratumumab to effectively target long-lived plasma cells as the source of ITP-mediating autoantibodies, and suggest broader clinical evaluation of daratumumab in this potential indication.</span></p></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10736671","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}

{"title":"Development of a Thalassemia International Prognostic Scoring System (TIPSS)","authors":"Angela Vitrano ,&nbsp;Khaled M. Musallam ,&nbsp;Antonella Meloni ,&nbsp;Mehran Karimi ,&nbsp;Shahina Daar ,&nbsp;Paolo Ricchi ,&nbsp;Silvia Costantini ,&nbsp;Efthymia Vlachaki ,&nbsp;Vito Di Marco ,&nbsp;Amal El-Beshlawy ,&nbsp;Mahmoud Hajipour ,&nbsp;Saqib Hussain Ansari ,&nbsp;Aldo Filosa ,&nbsp;Adriana Ceci ,&nbsp;Sylvia Titi Singer ,&nbsp;Zaki A. Naserullah ,&nbsp;Alessia Pepe ,&nbsp;Filippo Cademartiri ,&nbsp;Sebastiano Addario Pollina ,&nbsp;Salvatore Scondotto ,&nbsp;Aurelio Maggio","doi":"10.1016/j.bcmd.2022.102710","DOIUrl":"10.1016/j.bcmd.2022.102710","url":null,"abstract":"<div><p>A prognostic scoring system that can differentiate β-thalassemia patients based on mortality risk is lacking. We analysed data from 3145 β-thalassemia patients followed through a retrospective cohort design for the outcome of death. An <em>a priori</em><span> list of prognostic variables was collected. β Coefficients from a multivariate cox regression model were used from a development dataset (</span><em>n</em><span><span> = 2516) to construct a formula for a Thalassemia </span>International Prognostic Scoring System (TIPSS) which was subsequently applied to a validation dataset (</span><em>n</em><span><span> = 629). The median duration of observation was 10.0 years. The TIPSS score formula was constructed as exp (1.4 × heart disease + 0.9 × liver disease + 0.9 × diabetes + 0.9 × sepsis + 0.6 × alanine aminotransferase ≥42 IU/L + 0.6 × hemoglobin ≤9 g/dL + 0.4 × serum </span>ferritin ≥1850 ng/mL). TIPSS score thresholds of greatest differentiation were assigned as &lt;2.0 (low-risk), 2.0 to &lt;5.0 (intermediate-risk), and ≥5.0 (high-risk). The TIPSS score was a good predictor for the outcome of death in the validation dataset (AUC: 0.722, 95%CI: 0.641–0.804) and survival was significantly different between patients in the three risk categories (</span><em>P</em><span> &lt; 0.001). Compared to low-risk patients, the hazard ratio for death was 2.778 (95%CI: 1.335–5.780) in patients with intermediate-risk and 6.431 (95%CI: 3.151–13.128) in patients with high-risk. This study provides a novel tool to support mortality risk categorization for patients with β-thalassemia that could help management and research decisions.</span></p></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10736431","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}

{"title":"Hematologically important mutations: Leukocyte adhesion deficiency (second update)","authors":"Dirk Roos ,&nbsp;Karin van Leeuwen ,&nbsp;Manisha Madkaikar ,&nbsp;Priyanka M. Kambli ,&nbsp;Maya Gupta ,&nbsp;Vikram Mathews ,&nbsp;Amit Rawat ,&nbsp;Douglas B. Kuhns ,&nbsp;Steven M. Holland ,&nbsp;Martin de Boer ,&nbsp;Hirokazu Kanegane ,&nbsp;Nima Parvaneh ,&nbsp;Myriam Lorenz ,&nbsp;Klaus Schwarz ,&nbsp;Christoph Klein ,&nbsp;Roya Sherkat ,&nbsp;Mahbube Jafari ,&nbsp;Baruch Wolach ,&nbsp;Johan T. den Dunnen ,&nbsp;Taco W. Kuijpers ,&nbsp;M. Yavuz Köker","doi":"10.1016/j.bcmd.2023.102726","DOIUrl":"10.1016/j.bcmd.2023.102726","url":null,"abstract":"<div><p><span>Leukocyte adhesion<span><span><span><span> deficiency (LAD) is an immunodeficiency caused by defects in the adhesion of leukocytes (especially neutrophils) to the blood vessel wall. As a result, patients with LAD suffer from severe bacterial infections and </span>impaired wound healing<span>, accompanied by neutrophilia. In LAD-I, characterized directly after </span></span>birth by delayed separation of the </span>umbilical cord, mutations are found in </span></span><span><em>ITGB2</em></span><span>, the gene that encodes the β subunit (CD18) of the β</span>₂<span><span> integrins. In the rare LAD-II disease, the fucosylation of </span>selectin ligands is disturbed, caused by mutations in </span><span><em>SLC35C1</em></span><span>, the gene that encodes a GDP-fucose transporter of the Golgi system. LAD-II patients lack the H and Lewis Le</span>^a and Le^b<span><span> blood group antigens. Finally, in LAD-III, the conformational activation of the hematopoietically expressed β integrins is disturbed, leading to leukocyte and </span>platelet dysfunction. This last syndrome is caused by mutations in </span><span><em>FERMT3</em></span><span>, encoding the kindlin-3 protein in all blood cells, involved in the regulation of β integrin conformation. This article contains an update of the mutations that we consider to be relevant for the various forms of LAD.</span></p></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10742475","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}