Article
Hematology
Man-Chiu Poon
Summary: The study summarized evidence from three different sources demonstrating the efficacy and safety of rFVIIa in patients with GT without refractoriness or antibodies to platelets, supporting the label extension of rFVIIa as an alternative treatment when platelets are unavailable.
THROMBOSIS AND HAEMOSTASIS
(2021)
Article
Medicine, Research & Experimental
Xuanli Tang, Feng Wan, Qin Zhu, Tian Ye, Xue Jiang, Haichun Yang
Summary: The study found that IgG subclass was selectively deposited along GBM and/or TBM in DN, with the mixed type of IgG subclass deposition on TBM having more clinical significance. IgG subclass deposition is merely a manifestation or a consequence rather than a cause in DN.
EUROPEAN JOURNAL OF MEDICAL RESEARCH
(2022)
Article
Immunology
Biliana Todorova, Ophelie Godon, Eva Conde, Caitlin M. Gillis, Bruno Iannascoli, Odile Richard-Le Goff, Daniel Fiole, Lubka T. Roumenina, Jeanette H. W. Leusen, Andrew J. Murphy, Lynn E. Macdonald, Laurent L. Reber, Friederike Joensson, Pierre Bruhns
Summary: In mouse models of active systemic anaphylaxis, IgG-allergen immune complexes predominantly accumulate in the lungs. The accumulation of allergens in the lungs does not rely on IgG receptors, complement component C1q, neutrophils, or macrophages. Neutrophils and monocytes recruited to the lungs capture high amounts of allergens, leading to downregulation of surface IgG receptors and activation.
JOURNAL OF IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Clizia Chinello, Noortje de Haan, Giulia Capitoli, Barbara Trezzi, Antonella Radice, Lisa Pagani, Lucrezia Criscuolo, Stefano Signorini, Stefania Galimberti, Renato Alberto Sinico, Manfred Wuhrer, Fulvio Magni
Summary: Podocyte injury and proteinuria in idiopathic membranous nephropathy (IMN) are caused by an autoimmune reaction against podocyte antigens. This study systematically analyzed the IgG Fc glycosylation landscape in IMN patients and identified several glycan traits associated with the disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Kamuran Karaman, Eyup Yurekturk, Hadi Geylan, Akkiz Sahin Yasar, Serap Karaman, Huri Sema Aymelek, Mecnun Cetin, Ahmet Fayik Oner
Summary: This study investigated the genetic mutation types in 17 patients diagnosed with Glanzmann's thrombasthenia (GT) and found 12 patients with identified genetic mutations. Among these, 6 had the same type of mutation, while 4 had novel mutations not previously described. However, no significant association was found between the genetic mutations and clinical findings in these patients, indicating the need for further studies with a larger sample size to determine the relationship between genotypes and clinical presentations in GT patients.
Article
Respiratory System
Hyun Lee, Cara Kovacs, Andre Mattman, Zsuzsanna Hollander, Virginia Chen, Raymond Ng, Janice M. Leung, Don D. Sin
Summary: In patients with chronic obstructive pulmonary disease (COPD), IgG1 and IgG4 deficiencies are significantly associated with an increased risk of 1-year mortality, while IgG2 and IgG3 deficiencies do not significantly increase mortality rates.
RESPIRATORY RESEARCH
(2022)
Article
Genetics & Heredity
Dayan Wang, Panjian Lai, Qiaochun Lu, Mohammed A. El-Magd, Xiaobing Li
Summary: The c.1431C > T mutation in the ITGB3 gene causes three different alternative splicing patterns, which do not affect mRNA levels but directly lead to protein truncation and decreased expression. This mutation could be considered a pathogenic variant of Glanzmann's thrombasthenia.
Review
Immunology
Jana Sophia Buhre, Mareike Becker, Marc Ehlers
Summary: The development of inflammatory autoimmune diseases involves two steps, from harmless self-directed antibody responses to more inflammatory responses. Identifying biomarkers that signal the transition from the pre-disease to the disease stage can help determine the optimal time to initiate treatment and develop therapeutic strategies.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Medicine, Research & Experimental
Paul Cain, Lihua Huang, Yu Tang, Victor Anguiano, Yiqing Feng
Summary: IgG-based monoclonal antibody therapeutics have dominated the biotherapeutics field for decades. However, there is a lack of systematic evaluation of different IgG subclasses on manufacturability and long-term stability. This study evaluated 12 mAbs derived from three sets of variable regions, and identified the impact of IgG subclass on manufacturability and stability, which is important for therapeutic antibody development process.
Article
Biology
Yanxia Bi, Jian Su, Shengru Zhou, Yingjie Zhao, Yan Zhang, Huihui Zhang, Mingdong Liu, Aiwu Zhou, Jianrong Xu, Meng Pan, Yiming Zhao, Fubin Li
Summary: This study reveals the distinct impact of IgG subclass and Fc-Fc gamma R interaction on the pathogenic function of autoantibodies in different IgG4-mediated diseases. IgG4 has an ameliorative effect on the pathogenicity of anti-ADAMTS13 autoantibodies in thrombotic thrombocytopenic purpura (TTP) patients, but an unexpected exacerbating effect on the pathogenicity of anti-Dsg1 autoantibodies in pemphigus foliaceus (PF) models. A non-pathogenic anti-Dsg1 antibody variant optimized for Fc gamma R-mediated effector function can attenuate the skin lesions induced by pathogenic anti-Dsg1 antibodies by promoting the clearance of dead keratinocytes.
Article
Biochemical Research Methods
Si Liu, Yuanyuan Liu, Jiajing Lin, Yi Wang, Dong Li, Gui-Yan Xie, An-Yuan Guo, Bi-Feng Liu, Liming Cheng, Xin Liu
Summary: This study comprehensively characterized subclass-specific IgG glycosylation in colorectal cancer, gastric cancer, and esophageal cancer using liquid chromatography-tandem mass spectrometry. The findings revealed changes in IgG1 sialylation and IgG4 mono-galactosylation in all three cancers, as well as specific glycopeptides that could distinguish the cancer groups from controls. Bioinformatics analysis verified the differential expression of glycosyltransferase genes related to cancer progression.
JOURNAL OF PROTEOME RESEARCH
(2022)
Review
Immunology
Falk Nimmerjahn, Gestur Vidarsson, Mark S. Cragg
Summary: Humoral immune responses generate polyclonal antibodies with varied isotypes, epitope specificity, and affinity. Posttranslational modifications in antibody variable and constant domains can modify antigen specificity and antibody Fc-dependent functions. Understanding the impact of these modifications on antibody function is still limited, but it has implications for therapeutic antibody development. This Review provides insights into how IgG subclass and posttranslational modifications influence antibody activity and discusses their implications in designing therapeutic antibodies for different clinical indications.
Article
Medicine, General & Internal
Carmen Scheibenbogen, Franziska Sotzny, Jelka Hartwig, Sandra Bauer, Helma Freitag, Kirsten Wittke, Wolfram Doehner, Nadja Scherbakov, Madlen Loebel, Patricia Grabowski
Summary: An open trial on ME/CFS patients receiving self-administered s.c. IgG therapy showed clinical improvement in a subset of patients. Treatment efficacy was measured through fatigue and physical functioning assessments, with 5 patients showing clinical response at month 12.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Immunology
James C. Barton, Jackson Clayborn Barton, Luigi F. Bertoli, Ronald T. Acton
Summary: This study found that both IgG1 and IgG2 are major determinants of IgG levels in adults with IgG subclass deficiency, with significantly lower median IgG2 levels in patients with subnormal IgG1 or combined subnormal IgG1/IgG3 when IgG levels are < 7.00 g/L compared to >= 7.00 g/L.
Article
Medicine, General & Internal
Jehanzeb Ur Rehman, Fayyaz Hussain, Syed Kamran Mahmood, Qamar Un Nisa, Nighat Shahbaz, Mehreen Ali Khan
Summary: Glanzmann's thrombasthenia (GT) is a bleeding disorder that can be effectively treated with stem cell transplantation.
JCPSP-JOURNAL OF THE COLLEGE OF PHYSICIANS AND SURGEONS PAKISTAN
(2022)
Article
Hematology
Brigitte K. Flesch, Angelika Reil, Nuria Nogues, Carme Canals, Peter Bugert, Torsten J. Schulze, Elly Huiskes, Leendert Porcelijn, Petter Hoglund, Paul Ratcliffe, Marlies Schoenbacher, Hans Kerchrom, Josina Kellershohn, Behnaz Bayat
TRANSFUSION MEDICINE AND HEMOTHERAPY
(2020)
Review
Hematology
David E. Schmidt, Anke J. Lakerveld, Katja M. J. Heitink-Polle, Marrie C. A. Bruin, Gestur Vidarsson, Leendert Porcelijn, Masja de Haas
Article
Hematology
David E. Schmidt, Pernille Wendtland Edslev, Katja M. J. Heitink-Polle, Bart Mertens, Marrie C. A. Bruin, Rick Kapur, Gestur Vidarsson, C. Ellen van der Schoot, Leendert Porcelijn, Johanna G. van der Bom, Steen Rosthoj, Masja de Haas
Summary: The Childhood ITP Recovery Score was developed to predict transient versus persistent ITP in children with newly diagnosed ITP. The score showed good predictive performance in external validation and could be valuable for guiding clinical management.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2021)
Article
Hematology
David E. Schmidt, Katja M. J. Heitink-Polle, Bart Mertens, Leendert Porcelijn, Rick Kapur, C. Ellen van Der Schoot, Gestur Vidarsson, Johanna G. van Der Bom, Marrie C. A. Bruin, Masja de Haas
Summary: This study focused on predicting the response to IVIg treatment and ITP disease course in children, identifying 5 variables that predict ASR vs CSR, which improved discrimination of favorable ITP disease courses.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2021)
Article
Hematology
Thijs W. de Vos, Leendert Porcelijn, Suzanne Hofstede-van Egmond, Eva Pajkrt, Dick Oepkes, Enrico Lopriore, C. Ellen van der Schoot, Dian Winkelhorst, Masja de Haas
Summary: Fetal neonatal alloimmune thrombocytopenia (FNAIT) is a condition caused by maternal alloantibodies targeting human platelet antigens, which can result in severe bleeding in the unborn child. While anti-HPA-1a-mediated FNAIT tends to have a more severe clinical outcome, anti-HPA-5b may also be associated with severe neonatal bleeding symptoms. Further research, including a prospective study, is needed to fully understand the natural history of anti-HPA-5b mediated FNAIT.
BRITISH JOURNAL OF HAEMATOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Thijs W. de Vos, Dian Winkelhorst, Hans J. Baelde, Kyra L. Dijkstra, Rianne D. M. van Bergen, Lotte E. van der Meeren, Peter G. J. Nikkels, Leendert Porcelijn, C. Ellen van der Schoot, Gestur Vidarsson, Michael Eikmans, Rick Kapur, Carin van der Keur, Leendert A. Trouw, Dick Oepkes, Enrico Lopriore, Marie-Louise P. van der Hoorn, Manon Bos, Masja de Haas
Summary: This study found that untreated FNAIT cases showed more C4d deposition in the placenta, which may impact placental function and fetal growth. Histopathological examination revealed a certain proportion of placental delayed maturation in these cases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Medicine, General & Internal
Anne-Tess C. Jolink, Vivianne S. Nelson, Martin R. Schipperus, Sufia N. Amini, Gestur Vidarsson, C. Ellen van der Schoot, Leendert Porcelijn, Masja de Haas, Rick Kapur
Summary: Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder characterized by platelet destruction and MK impairment. The challenging therapeutic management and potential complications underscore the importance of research into personalized treatment strategies and predictive markers for treatment responses.
JOURNAL OF CLINICAL MEDICINE
(2021)
Review
Cell Biology
Vivianne S. Nelson, Anne-Tess C. Jolink, Sufia N. Amini, Jaap Jan Zwaginga, Tanja Netelenbos, John W. Semple, Leendert Porcelijn, Masja de Haas, Martin R. Schipperus, Rick Kapur
Summary: ITP is an autoimmune bleeding disorder characterized by low platelet levels, involving mechanisms like autoantibody-dependent and cytotoxic T cell mediated platelet clearance. Interestingly, platelets not only mediate hemostasis, but also modulate inflammatory and immunological processes, potentially playing an immuno-modulatory role in ITP. Platelets and platelet microparticles may be involved in promoting inflammation, stimulating immune responses, and contributing to disrupted immune balance and impaired thrombopoiesis in ITP, providing new avenues for research and potential therapies.
Article
Hematology
Sufia N. Amini, Leendert Porcelijn, Annemieke Sobels, Marina Kartachova, Masja de Haas, Jaap Jan Zwaginga, Martin R. Schipperus
Summary: This study investigated the association between anti-GP antibodies and platelet sequestration patterns and clearance rate in ITP patients. The results showed that anti-GPV antibodies are associated with a splenic sequestration pattern, and in patients where antibodies were present, the clearance rate was higher in patients with a splenic sequestration.
Article
Hematology
Thijs L. J. van Osch, Janita J. Oosterhoff, Arthur E. H. Bentlage, Jan Nouta, Carolien A. M. Koeleman, Dionne M. Geerdes, Juk Yee Mok, Sebastiaan Heidt, Arend Mulder, Wim J. E. van Esch, Rick Kapur, Leendert Porcelijn, Ellen van der Schoot, Masja de Haas, Manfred Wuhrer, Jan Voorberg, Gestur Vidarsson
Summary: Approximately 20% of patients receiving multiple platelet transfusions develop platelet alloantibodies, which can lead to platelet refractoriness. Factors such as antibody glycosylation and the breadth of the polyclonal immune response may affect complement activation and clearance of donor platelets.
Letter
Hematology
T. Langerak, G. J. Bakker, L. Porcelijn, M. N. Lauw, R. J. van de Laar, M. Eefting
THROMBOSIS RESEARCH
(2022)
Article
Pediatrics
Inez M. Vanholder, Ginette M. Ecury-Goossen, Jop Admiraal, Leendert Porcelijn, Rosalina Ml van Spaendonk, Samantha C. Gouw
JOURNAL OF PAEDIATRICS AND CHILD HEALTH
(2022)
Editorial Material
Hematology
Sufia N. Amini, Vivianne S. Nelson, Leendert Porcelijn, Tanja Netelenbos, Jaap Jan Zwaginga, Masja de Haas, Martin R. Schipperus, Rick Kapur
Summary: ITP is an autoimmune bleeding disorder characterized by platelet clearance in the spleen and liver. Thrombopoietin (TPO) levels remain low in ITP. The role of GPIb antibodies in relation to platelet hepatic sequestration and TPO levels in ITP remains unclear. This study found a positive association between GPIb antibodies and TPO levels as well as platelet hepatic sequestration in patients with severe thrombocytopenic ITP.
Article
Hematology
Thijs L. J. van Osch, Tamas Pongracz, Dionne M. Geerdes, Juk Yee Mok, Wim J. E. van Esch, Jan Voorberg, Rick Kapur, Leendert Porcelijn, Jean-Louis H. Kerkhoffs, Pieter F. van Der Meer, C. Ellen van Der Schoot, Masja de Haas, Manfred Wuhrer, Gestur Vidarsson
Summary: The Fc glycosylation profile of anti-HLA class I antibodies formed after platelet transfusion varies between patients, and could potentially explain the variation in clinical severity.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2022)
Article
Hematology
Thijs W. de Vos, Dian Winkelhorst, Valgerdur Arnadottir, Johanna G. van Der Bom, Carme Canals Suris, Camila Caram-Deelder, Emoke Deschmann, Helen E. Haysom, Hem Birgit C. Hverven, Jana Lozar Krivec, Zoe K. McQuilten, Eduardo Muniz-Diaz, Nuria Nogues, Dick Oepkes, Leendert Porcelijn, C. Ellen van Der Schoot, Matthew Saxonhouse, Martha Sola-Visner, Eleonor Tiblad, Heidi Tiller, Erica M. Wood, Vanessa Young, Mojca Zeleznik, Masja de Haas, Enrico Lopriore
Summary: Management of FNAIT varies greatly between international centres, with HPA-matched transfusions resulting in a larger median platelet count increment than HPA-unmatched transfusions, but whether HPA matching is also associated with a reduced risk of bleeding remains unknown.
LANCET HAEMATOLOGY
(2022)