Article
Immunology
Rupesh Raina, Guneive Mangat, Gordon Hong, Raghav Shah, Nikhil Nair, Brian Abboud, Sumedha Bagga, Sidharth Kumar Sethi
Summary: Atypical hemolytic uremic syndrome (aHUS) is an important form of thrombotic microangiopathy (TMA) that often leads to acute kidney injury (AKI). Anti-factor H associated aHUS is a specific subtype of aHUS caused by complement factor H gene deletions and the presence of anti-factor H antibodies. However, not all patients with this subtype have the CFHR1/R3 deletion. Dysregulation of the complement system, particularly the alternative pathway, due to factor H dysfunction can result in inflammatory or autoimmune diseases. Treatment options such as plasma exchange therapy, Eculizumab, and immunosuppressants have shown positive effects in patients with this disease. Further advancements in the diagnosis and management of anti-factor H associated aHUS are needed due to its genetic predisposition.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Urology & Nephrology
Gema Ariceta, Bradley P. Dixon, Seong Heon Kim, Gaurav Kapur, Teri Mauch, Stephan Ortiz, Marc Vallee, Andrew E. Denker, Hee Gyung Kang, Larry A. Greenbaum
Summary: Ravulizumab rapidly improved hematologic and kidney parameters in complement inhibitor-naive children with atypical hemolytic uremic syndrome, showing no unexpected safety concerns.
KIDNEY INTERNATIONAL
(2021)
Article
Immunology
Sigridur Sunna Aradottir, Ann-Charlotte Kristoffersson, Lubka T. Roumenina, Anna Bjerre, Pavlos Kashioulis, Runolfur Palsson, Diana Karpman
Summary: The study indicates that FD inhibition can effectively block complement overactivation induced by FB gain-of-function mutations.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Sarah de Jong, Anita de Breuk, Bjorn Bakker, Suresh Katti, Carel B. Hoyng, Sara C. Nilsson, Anna M. Blom, Lambert P. van den Heuvel, Anneke I. den Hollander, Elena B. Volokhina
Summary: Complement factor I (FI) is a key regulator of the complement system, and its dysfunction is associated with increased complement activation and diseases like AMD and aHUS. This study identified CFI gene variants in AMD and aHUS, with more than half leading to reduced FI secretion levels. Functional analysis of 11 rare missense variants revealed 8 variants with impaired C3b degradation, suggesting their likely pathogenicity. Monitoring iC3b in a degradation assay is a useful tool for assessing the functional impact of CFI variants.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Pediatrics
Sigridur Sunna Aradottir, Ann-Charlotte Kristoffersson, Erik Linner, Diana Karpman
Summary: This study identified a heterozygous genetic variant, M514R, in factor H-related protein 5 (CFHR5), as well as a homozygous deletion of CFHR3/CFHR1 and antibodies to factor H, in a child with atypical hemolytic uremic syndrome (aHUS). The patient's serum exhibited low levels of FHR5 and induced hemolysis, which decreased when recombinant human rFHR5 was added. The CFHR5 M514R variant showed a decreased secretion of the protein, but increased protein levels in cell lysates. These findings suggest that low levels of FHR5 may contribute to complement activation in aHUS.
PEDIATRIC NEPHROLOGY
(2023)
Article
Immunology
Shirley Pollack, Israel Eisenstein, Adi Mory, Tamar Paperna, Ayala Ofir, Hagit Baris-Feldman, Karin Weiss, Nora Veszeli, Dorottya Csuka, Revital Shemer, Fabian Glaser, Zoltan Prohaszka, Daniella Magen
Summary: The study identified a rare novel homozygous activating deletion in the C3 gene associated with atypical hemolytic uremic syndrome (aHUS), highlighting the critical role of the disrupted C3-TED domain in the disease mechanism.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Gautier Breville, Ido Zamberg, Salima Sadallah, Caroline Stephan, Belen Ponte, Jorg D. Seebach
Summary: This study describes the potential pathogenic role of Ig4 autoantibodies in complement-mediated thrombotic microangiopathy in a patient with IgG4-related disease. The patient was successfully treated with plasmapheresis, corticosteroids, and cyclophosphamide, achieving remission. The results suggest a link between genetic predispositions such as CFHR1 and CFHR4 gene deletions and the formation of inhibitory anti-Factor H IgG4 antibodies.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Rossella Piras, Elisabetta Valoti, Marta Alberti, Elena Bresin, Caterina Mele, Matteo Breno, Lucia Liguori, Roberta Donadelli, Miriam Rigoldi, Ariela Benigni, Giuseppe Remuzzi, Marina Noris
Summary: This study found that uncommon CFH-CFHR genomic rearrangements are common in patients with primary aHUS but rare in those with secondary forms. Patients with CFH-CFHR genomic rearrangements have a poorer prognosis but respond to anti-complement therapy.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Medicine, General & Internal
Hao Wu, Sensen Su, Lin Li, Li Zhang
Summary: Adult-onset aHUS caused by CFB gene mutation is rare and serious, requiring timely diagnosis and treatment. This case was successfully treated with interventions such as plasma exchange and continuous renal replacement therapy, highlighting the importance of early detection and intervention in improving patient outcomes.
Article
Immunology
Margarita Lopez-Trascasa, Angel Alonso-Melgar, Marta Melgosa-Hijosa, Laura Espinosa-Roman, Maria Dolores Lledin-Barbancho, Eugenia Garcia-Fernandez, Santiago Rodriguez de Cordoba, Pilar Sanchez-Corral
Summary: Pathogenic gain-of-function mutations in complement Factor B were found to be the cause of atypical HUS in 2007. A four-month-old boy diagnosed with hypocomplementemic aHUS in 2000 suffered severe complications and end-stage renal disease by the age of 3, eventually undergoing a combined liver and kidney transplantation in 2009. After experiencing post-transplant complications, including B-cell non-Hodgkin lymphoma and liver rejection, the patient currently maintains normal kidney and liver functions 12 years post-surgery, suggesting that CLKT was an acceptable therapeutic option.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Medicine, General & Internal
Lara Kollbrunner, Patricia Hirt-Minkowski, Javier Sanz, Elena Bresin, Thomas J. Neuhaus, Helmut Hopfer, Andreas W. Jehle
Summary: This case report describes a 21-year-old man with Lipoprotein Glomerulopathy (LPG) who developed Atypical Hemolytic Uremic Syndrome (aHUS). Functional complement assay revealed overactivation of the complement system, and genetic analysis identified a homozygous aHUS risk allele for complement factor-H related 1 (CFHR1), CFHR1*B. This is the first report of aHUS in a patient with LPG.
FRONTIERS IN MEDICINE
(2021)
Article
Hematology
Vicky Brocklebank, Patrick R. Walsh, Kate Smith-Jackson, Thomas M. Hallam, Kevin J. Marchbank, Valerie Wilson, Theophile Bigirumurame, Tina Dutt, Emma K. Montgomery, Michal Malina, Edwin K. S. Wong, Sally Johnson, Neil S. Sheerin, David Kavanagh
Summary: Our study demonstrates the efficacy of eculizumab in improving ESKD-free survival in patients with complement-mediated atypical hemolytic uremic syndrome. The response to eculizumab treatment is influenced by the underlying genotype and clinical characteristics.
Article
Biochemistry & Molecular Biology
I-Ru Chen, Chiu-Ching Huang, Siang-Jyun Tu, Guei-Jane Wang, Ping-Chin Lai, Ya-Ting Lee, Ju-Chen Yen, Ya-Sian Chang, Jan-Gowth Chang
Summary: This single-cell sequencing study confirms the importance of immune cell dysregulation in the pathogenesis of aHUS, providing valuable insights into molecular mechanisms and potential new diagnostic and disease activity markers.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Urology & Nephrology
Thomas Barbour, Marie Scully, Gema Ariceta, Spero Cataland, Katherine Garlo, Nils Heyne, Yosu Luque, Jan Menne, Yoshitaka Miyakawa, Sung-Soo Yoon, David Kavanagh
Summary: Ravulizumab demonstrates long-term efficacy and safety in adults with aHUS, providing additional clinical benefits beyond 6 months of treatment, with most adverse events occurring early during the initial evaluation period and decreasing over time.
KIDNEY INTERNATIONAL REPORTS
(2021)
Article
Urology & Nephrology
Massimo Cugno, Valentina Capone, Samantha Griffini, Elena Grovetti, Giulia Pintarelli, Luigi Porcaro, Emilio Clementi, Gianluigi Ardissino
Summary: This study reports on the experience with eculizumab maintenance treatment in patients with aHUS. The interval between eculizumab doses was adjusted based on CCP activity, with the goal of maintaining CCP activity below 30% to prevent relapse. Patients who received eculizumab regularly at tailored intervals showed no relapse during the observation period, and there was an inverse correlation between CCP activity and eculizumab circulating levels.
JOURNAL OF NEPHROLOGY
(2022)
Article
Multidisciplinary Sciences
Luc de Chaisemartin, Tchao Meatchi, Georgia Malamut, Fahima Fernani-Oukil, Frederique Hosking, Dorothee Rault, Fabienne Bellery, Christophe Cellier, Marie-Agnes Dragon-Durey
Article
Immunology
M. Senant, H. Rostane, F. Fernani-Oukil, F. Hosking, F. Bellery, A. Courchinoux, E. Tartour, L. Darnige, M-A. Dragon-Durey
JOURNAL OF IMMUNOLOGY RESEARCH
(2015)
Review
Urology & Nephrology
Marie-Agnes Dragon Durey, Aditi Sinha, Shambhuprasad Kotresh Togarsimalemath, Arvind Bagga
NATURE REVIEWS NEPHROLOGY
(2016)
Article
Urology & Nephrology
Shambhuprasad K. Togarsimalemath, Sidharth K. Sethi, Rajan Duggal, Moglie Le Quintrec, Pranaw Jha, Regis Daniel, Florence Gonnet, Shyam Bansal, Lubka T. Roumenina, Veronique Fremeaux-Bacchi, Vijay Kher, Marie-Agnes Dragon-Durey
KIDNEY INTERNATIONAL
(2017)
Article
Urology & Nephrology
Maria-Chiara Marinozzi, Sophie Chauvet, Moglie Le Quintrec, Morgane Mignotet, Florent Petitprez, Christophe Legendre, Mathilde Cailliez, Georges Deschenes, Michel Fischbach, Alexandre Karras, Francois Nobili, Christine Pietrement, Marie-Agnes Dragon-Durey, Fadi Fakhouri, Lubka T. Roumenina, Veronique Fremeaux-Bacchi
KIDNEY INTERNATIONAL
(2017)
Review
Urology & Nephrology
Timothy H. J. Goodship, H. Terence Cook, Fadi Fakhouri, Fernando C. Fervenza, Veronique Fremeaux-Bacchi, David Kavanagh, Carla M. Nester, Marina Noris, Matthew C. Pickering, Santiago Rodriguez de Cordoba, Lubka T. Roumenina, Sanjeev Sethi, Richard J. H. Smith
KIDNEY INTERNATIONAL
(2017)
Review
Rheumatology
Samuel Deshayes, Nicolas Martin Silva, Valerie Chatelet, Sylvain Chantepie, Moglie Le Quintrec, Francois Comoz, Frank Bridoux, Marie-Agnes Dragon-Durey, Achille Aouba
CLINICAL RHEUMATOLOGY
(2018)
Letter
Immunology
Giovanna Clavarino, Arnaud Gauthier, Thomas Hellmark, Pierre-Louis Carron, Diane Giovannini, Sophie Colliard, Marie-Agnes Dragon-Durey, Marten Segelmark, Jean-Yves Cesbron, Chantal Dumestre-Perard
EUROPEAN JOURNAL OF IMMUNOLOGY
(2018)
Article
Pediatrics
Shambhuprasad K. Togarsimalemath, Ali Si-Mohammed, Mamta Puraswani, Aarti Gupta, Astrid Vabret, Sandrine Liguori, Patricia Mariani-Kurkdjian, Arvind Bagga, Marie-Agnes Dragon-Durey
PEDIATRIC RESEARCH
(2018)
Review
Medicine, General & Internal
V. Joste, M. -A. Dragon-Durey, L. Darnige
REVUE DE MEDECINE INTERNE
(2018)
Article
Pediatrics
Priyanka Khandelwal, Aarti Gupta, Aditi Sinha, Savita Saini, Pankaj Hari, Marie-Agnes Dragon Durey, Arvind Bagga
PEDIATRIC NEPHROLOGY
(2015)
Article
Biochemical Research Methods
Marie Senant, Pauline Bordereau, Eric Tartour, Marie-Agnes Dragon-Durey
JOURNAL OF IMMUNOLOGICAL METHODS
(2019)
Article
Immunology
Sophie Chauvet, Lubka T. Roumenina, Pierre Aucouturier, Maria-Chiara Marinozzi, Marie-Agnes Dragon-Durey, Alexandre Karras, Yahsou Delmas, Moglie Le Quintrec, Dominique Guerrot, Noemie Jourde-Chiche, David Ribes, Pierre Ronco, Frank Bridoux, Veronique Fremeaux-Bacchi
FRONTIERS IN IMMUNOLOGY
(2018)
Article
Oncology
Marie Senant, Delphine Giusti, Laurence Weiss, Marie-Agnes Dragon-Durey
BULLETIN DU CANCER
(2016)
Article
Medical Laboratory Technology
Marie-Agnes Dragon-Durey, Nicole Fabien, Georges Chyderiotis, Lucile Musset, Bach-Nga Pham, Niels Olsson
ANNALES DE BIOLOGIE CLINIQUE
(2017)