Article
Pediatrics
Pedro Simao Coelho, Catarina Gouveia, Marta Valente Pinto, Conceicao Neves, Ana Isabel Cordeiro, Joao Farela Neves
Summary: C3 is a crucial protein in the complement system. Congenital C3 deficiency is extremely rare and presents with recurrent, severe infections, which should be considered as a possible cause of recurrent pyogenic infections. We report a case of a patient with a novel C3 gene mutation causing complete C3 deficiency, impaired complement system activation, and recurrent infections.
FRONTIERS IN PEDIATRICS
(2022)
Review
Immunology
Yesim Yilmaz Demirdag, Sudhir Gupta
Summary: Bacterial respiratory tract infections are common in primary antibody deficiencies (PADs) but often overlooked in healthy individuals. This review focuses on infections in relatively common PADs, discussing diagnostic challenges and management strategies to prevent infections.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Immunology
Kristina Schulz, Marten Trendelenburg
Summary: This systematic review provides an overview of the role of C1q knockout mice in disease models and potential target diseases for treatment strategies focusing on C1q. The study found that C1q is protective against autoimmune diseases and infections, but may have beneficial effects on diseases such as neurodegenerative disorders. However, depleting and/or inhibiting C1q may also result in some side effects.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Rheumatology
Sulaiman M. Al-Mayouf, Hajar A. Alreefi, Tuqa A. Alsinan, Ghada AlSalmi, Abdulaziz AlRowais, Waleed Al-Herz, Anas M. Alazami, Abdullah Alsonbul, Hamoud Al-Mousa
Summary: This study reviewed 39 pediatric patients with lupus manifestations associated with primary immunodeficiency diseases (PIDs), finding that most patients had complement deficiencies and common clinical features included mucocutaneous lesions, arthritis, and lung involvement. The study recommends immunological work-up and genetic testing for patients presenting with lupus symptoms early in life, with a family history of SLE, or experiencing recurrent infections.
MODERN RHEUMATOLOGY
(2021)
Review
Immunology
Andrea Balduit, Anna Monica Bianco, Alessandro Mangogna, Anna Maria Zicari, Lucia Leonardi, Bianca Laura Cinicola, Martina Capponi, Alberto Tommasini, Chiara Agostinis, Adamo Pio d'Adamo, Roberta Bulla
Summary: Primary complement system (C) deficiencies are rare but associated with an increased risk of infections. This study presented a case of a ten-year-old boy infected by Neisseria meningitidis B and with reduced C activity, and identified two pathogenetic variants in the C7 gene.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Li Zhong, Xuan Sheng, Wanbing Wang, Yanzhong Li, Rengong Zhuo, Kai Wang, Lianshuai Zhang, Dan-Dan Hu, Yujuan Hong, Linting Chen, Hengjun Rao, Tingting Li, Muyang Chen, Zhihao Lin, Yun-wu Zhang, Xin Wang, Xiao-Xin Yan, Xiaochun Chen, Guojun Bu, Xiao-Fen Chen
Summary: This study reveals that TREM2 attenuates the activation of classical complement cascade by binding to its initiator C1q, providing mechanistic insights into the protective roles of TREM2 against AD pathogenesis. The formation of TREM2-C1q complexes in the human AD brains is associated with lower C3 deposition but higher amounts of synaptic proteins. Trem2 haploinsufficiency in mice increases complement-mediated microglial engulfment of synapses and accelerates synaptic loss, while administration of a TREM2 peptide rescues synaptic impairments in AD mouse models.
Article
Surgery
William M. Baldwin, Anna Valujskikh, Robert L. Fairchild
Summary: Initially believed to be solely part of the C1 complex initiating the complement cascade, C1q was later found to play a crucial role as a pattern recognition receptor in facilitating clearance of apoptotic cells and preventing immune recognition of autoantigens. This dual function of C1q has significant implications in transplantation and may potentially be explored as a therapeutic target to modulate immune responses.
AMERICAN JOURNAL OF TRANSPLANTATION
(2021)
Article
Immunology
Zefan Wang, Xiaoyu Wu, Tian Yan, Ming Liu, Wenhua Yu, Quan Du, Wei Hu, Yongke Zheng, Zuyong Zhang, Keyi Wang, Xiaoqiao Dong
Summary: This study aimed to investigate the effects of plasma C1q levels on hemorrhagic severity and functional outcome in patients with ICH. The results showed that plasma C1q levels were closely related to the severity and poor prognosis of ICH at 3 months. Plasma C1q levels may serve as a promising prognostic predictor for ICH.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Neurosciences
Robert A. J. Byrne, Megan Torvell, Nikoleta Daskoulidou, Dina Fathalla, Eirini Kokkali, Sarah M. Carpanini, B. Paul Morgan
Summary: Recent studies have shown that complement plays important roles in synaptic pruning, with C1q initiating complement activation on synapses and C3 fragments tagging them for removal. The development of sensitive assays for quantification of C1q in rodent models of AD is crucial for further understanding the role of C1q in disease pathogenesis and as a potential biomarker.
MOLECULAR NEUROBIOLOGY
(2021)
Article
Immunology
Hongjun Ba, Huimin Peng, Liangping Cheng, Yuese Lin, Xuandi Li, Xiufang He, Shujuan Li, Huishen Wang, Youzhen Qin
Summary: This case report describes a 7-month-old infant presenting with symptoms of TM infection including recurrent cough, fever, and rash. Whole exome sequencing revealed complex mutations in the patient's CARD9 gene, but symptoms significantly improved after voriconazole treatment.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Immunology
Mark Ballow, Silvia Sanchez-Ramon, Jolan E. Walter
Summary: Primary immunodeficiencies (PIDs) are genetic immune errors determined at birth, while secondary immunodeficiencies (SIDs) are acquired diseases with decreased immune cell counts. Distinguishing between primary and secondary antibody deficiencies is crucial in the era of immune-modulating biologicals. This article explores the crossovers between SIDs and PIDs, and discusses the challenges in diagnosis and treatment.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Immunology
Tinsae Alemayehu, Netsanet Azene Gebeyehu
Summary: This report describes the first case of major histocompatibility complex type I deficiency in a child of black African descent. The patient, a three-year-old Ethiopian boy, presented with recurrent sinopulmonary infections. Genetic analysis confirmed autosomal recessive inheritance. The report also provides a summary of the epidemiology, presentation, diagnosis, and management principles of this disorder.
JOURNAL OF CLINICAL IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Maria Radanova, Vasil Vasilev, Galya Mihaylova, Mariya Kosturkova, Uday Kishore, Lubka Roumenina
Summary: Anti-C1q autoantibodies are important biomarkers in lupus nephritis and are associated with the severity of renal injury.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Immunology
Su Han Lum, Reem Elfeky, Federica R. Achini, Adriana Margarit-Soler, Bianca Cinicola, Inigo Perez-Heras, Zohreh Nademi, Terry Flood, Tim Cheetham, Austen Worth, Waseem Qasim, Rakesh Amin, Kanchan Rao, Robert Chiesa, Robbert G. M. Bredius, Persis Amrolia, Mario Abinun, Sophie Hambleton, Paul Veys, Andrew R. Gennery, Arjan Lankester, Mary Slatter
Summary: This multicenter retrospective study investigated the occurrence of post-HCT autoimmune diseases in 596 children with PID. The study found that the incidence of post-HCT AD was 11% at 8 years post-HCT, with a median onset time of 2.2 years. Older age at transplant and T cell-depleted graft were significant predictors of post-HCT AD.
JOURNAL OF CLINICAL IMMUNOLOGY
(2021)
Article
Immunology
Sally Mahgoub Khalil, Sami Aqel, Dalal Sideeg Mudawi, Hassan Mobayed, Maryam Ali Al-Nesf
Summary: This case report highlights the importance of public health awareness and early detection in rare diseases, as it presents the first confirmed case of C7 deficiency in Qatar. It emphasizes the need for healthcare practitioners and communities to be informed about such conditions in order to prevent their consequences.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Cleo C. L. van Aanhold, Angela Koudijs, Kyra L. Dijkstra, Ron Wolterbeek, Jan A. Bruijn, Cees van Kooten, Hans J. Baelde
Summary: The study found that transfection with sFLT1 did not aggravate renal fibrosis and peritubular capillary loss, but reduced the expression of pro-fibrotic and pro-inflammatory markers. sFLT1 mRNA levels were not correlated with interstitial fibrosis or PTC loss in human samples.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Rheumatology
Theresa Kissel, Rene E. M. Toes, Thomas W. J. Huizinga, Manfred Wuhrer
Summary: Glycosylation is a common modification that affects protein stability and interactions. It plays a significant role in rheumatic diseases, influencing inflammatory processes and disease progression. Understanding the impact of glycosylation on plasma proteins, cells, and tissues opens up potential interventions for the treatment of these diseases.
NATURE REVIEWS RHEUMATOLOGY
(2023)
Article
Multidisciplinary Sciences
Louise Pierneef, Anouk van Hooij, Danielle de Jong, Elisa M. Tjon Kon Fat, Krista E. van Meijgaarden, Elisa Petruccioli, Valentina Vanini, Anna H. E. Roukens, Delia Goletti, Paul L. A. M. Corstjens, Simone A. Joosten, Annemiek Geluk, BEAT COVID Study Grp
Summary: Diagnostic services for TB and COVID-19 are not easily accessible in low-resource settings. This study demonstrates the potential of non-sputum lateral flow assays as adjunct diagnostics and treatment monitoring for both diseases based on quantitative detection of multiple host biomarkers.
Article
Rheumatology
Sophie I. E. Liem, Sam Neppelenbroek, Cynthia M. Fehres, Brigitte A. Wevers, Rene E. M. Toes, Cornelia F. Allaart, Tom W. J. Huizinga, Hans Ulrich Scherer, Jeska K. De Vries-Bouwstra
Summary: Early diagnosis of systemic sclerosis (SSc) is important. The most frequent SSc-specific autoantibodies are anti-centromere antibodies (ACA) and anti-topoisomerase I antibodies (ATA). ATA is associated with severe disease course. More detailed characterisation of the ATA-response in SSc might improve prognostication.
Article
Rheumatology
Frederique Ponchel, Laurence Duquenne, Xuanxiao Xie, Diane Corscadden, Farag Shuweihdi, K. Mankia, L. A. Trouw, Paul Emery
Summary: In this study, the researchers performed multiple autoantibody analysis to predict and determine the time of progression to inflammatory arthritis (IA). The results showed that multiple autoantibody testing provided added value and allowed for more specific stratification in identifying progressors to clinical disease for intervention studies.
Letter
Rheumatology
Tineke J. van Wesemael, Sanne Reijm, Atsushi Kawakami, Annemarie L. Dorjee, Gerrie Stoeken, Takahiro Maeda, Shin-ya Kawashiri, Tom W. J. Huizinga, Mami Tamai, Rene E. M. Toes, Diane van der Woude
ANNALS OF THE RHEUMATIC DISEASES
(2023)
Article
Immunology
Miles D. Holborough-Kerkvliet, Sanne Kroos, Renee van de Wetering, Rene E. M. Toes
Summary: Autoimmune diseases are characterized by a breakdown of immunological tolerance to self, resulting in an abnormal immune response to self-antigens. The pathogenesis is driven by a complex interaction between autoreactive B and T cells. B cell targeting therapies, such as Rituximab, have shown efficacy in reducing symptoms of autoimmune diseases, but can also lead to infections. Therefore, antigen-specific approaches to target autoreactive cells are being investigated.
IMMUNOLOGY LETTERS
(2023)
Article
Multidisciplinary Sciences
Leoni Abendstein, Douwe J. Dijkstra, Rayman T. N. Tjokrodirijo, Peter A. van Veelen, Leendert A. Trouw, Paul J. Hensbergen, Thomas H. Sharp
Summary: The authors used cryoEM and MS techniques to investigate IgG3-mediated complement activation and provide the first structural insights into IgG3. IgG3 is distinct from other IgG subclasses due to its extended hinge, allotypic diversity, and enhanced effector functions. However, the lack of structural information has limited its use as an immunotherapeutic candidate.
NATURE COMMUNICATIONS
(2023)
Article
Medicine, Research & Experimental
Sanne Reijm, Joanneke C. Kwekkeboom, Nienke J. Blomberg, Jolien Suurmond, Diane van der Woude, Rene E. M. Toes, Hans U. Scherer
Summary: This study visualizes the B cell response against posttranslational modification antigens in autoimmune diseases. The results demonstrate extensive cross-reactivity of B cells against different antigens and the presence of PTM-directed plasmablasts in patients. The expression of CXCR3 suggests the potential involvement of chemokines in this process.
Article
Rheumatology
Corrie M. Wortel, Sophie I. E. Liem, Nina M. van Leeuwen, Maaike Boonstra, Cynthia M. Fehres, Lauran Stoeger, Tom W. J. Huizinga, Rene E. M. Toes, Jeska De Vries-Bouwstra, Hans U. Scherer
Summary: This study investigates the autoreactive B cell responses in ATA-positive and ACA-positive SSc patients. The results show that ATA-positive patients exhibit a more active B cell response, which is associated with the presence and severity of ILD. This may explain the differential responsiveness to B cell depleting therapy.
Article
Immunology
Nienke Oskam, Pleuni Ooijevaar-de Heer, Ninotska I. L. Derksen, Simone Kruithof, Steven W. de Taeye, Gestur Vidarsson, Sanne Reijm, Theresa Kissel, Rene E. M. Toes, Theo Rispens
Summary: This study systematically investigated human IgM-mediated complement activation and found that hexameric IgM outperformed pentameric IgM and IgG1 in complement activation at low antigen densities, highlighting the importance of IgM in immunity.
JOURNAL OF IMMUNOLOGY
(2022)
Article
Medical Laboratory Technology
Tirsa T. van Duijl, L. Renee Ruhaak, Cees van Kooten, Johan W. de Fijter, Christa M. Cobbaert
Summary: This study explored the potential of LC-MS/MS as a next-generation technology for multiplex urinary protein measurement. It overcomes nonselectivity and lack of standardization by directly measuring well-defined molecular proteins.
JOURNAL OF APPLIED LABORATORY MEDICINE
(2022)
Article
Gastroenterology & Hepatology
Maaike Biewenga, Sebastiaan Heidt, Manon Vergunst, Camiel M. J. Marijnissen, Rob A. de Man, Annemiek A. van der Eijk, Adriaan J. van der Meer, Leendert A. Trouw, Bart van Hoek
Summary: This study assessed the levels of B cell activating factor of the tumour necrosis family (BAFF), IL-21, and circulating B cell populations in patients with autoimmune hepatitis (AIH) and identified different immunological phenotypes. Patients in the high IL-21 group had the poorest treatment response and a risk of developing PSC variant syndrome.
Article
Immunology
Douwe Jan Dijkstra, A. Inkeri Lokki, Lobke Marijn Gierman, Nicole Veronique Borggreven, Carin van der Keur, Michael Eikmans, Kyra Andrea Gelderman, Hannele Laivuori, Ann-Charlotte FINNPEC Core Investigator Grp, Ann-Charlotte Iversen, Marie-Louise P. van der Hoorn, Leendert Adrianus Trouw
Summary: Preeclampsia (PE) may be associated with decreased levels of C1q and FH, which are related to placental dysfunction and immune response.
FRONTIERS IN IMMUNOLOGY
(2022)
Meeting Abstract
Biochemistry & Molecular Biology
Douwe Dijkstra, Inkeri Lokki, Lobke Gierman, Nicole Borggreven, Carin van der Keur, Hannele Laivuori, Finnpec Board, Ann-Charlotte Iversen, Marie van der Hoorn Louise, Leendert Trouw
MOLECULAR IMMUNOLOGY
(2022)