Characterization of a novel genetic defect causing plasma cell deficiency

Abstract

Event Abstract Back to Event Characterization of a novel genetic defect causing plasma cell deficiency Desirée Schubert1, 2*, Janine Kemming1, Sarah Hassdenteufel3, Marie-Christine Klein3, Johannes Kühn1, Manfred Fliegauf1, Sandra Winzer1, Alejandro Schäffer4, Jennifer Puck5, Robert Hostoffer6, Anna Köttgen7, Marta Rizzi8, Hermann Eibel1, Richard Zimmermann3 and Bodo Grimbacher1 1 Center for Chronic Immunodeficiency, University Medical Center Freiburg, Germany 2 Spemann Graduate School of Biology and Medicine, Freiburg University, Germany 3 Medical Biochemistry & Molecular Biology, Saarland University, Homburg, Germany 4 National Library of Medicine, National Institutes of Health, Bethesda, Maryland, United States 5 Department of Pediatrics, UCSF Benioff Children's Hospital, University of California San Francisco, United States 6 University Hospitals Case Medical Center, Cleveland, Ohio, United States 7 Department of Medicine, Division of Nephrology, University Medical Center Freiburg, Germany 8 Department of Rheumatology and Clinical Immunology, University Medical Center Freiburg, Germany Common variable immunodeficiency (CVID) is the most frequent primary immunodeficiency in humans. It is characterized by hypogammaglobulinemia, absent vaccination responses and recurrent infections. We are working on the identification of the genetic defect in a family with autosomal dominant CVID. The clinical phenotype is mostly restricted to severe recurrent infections of the upper and lower respiratory tract. Flow cytometric analysis revealed that the patients have normal B and T cell populations in the periphery. However, in in vitro activation assays, the patient’s B cells were less capable of generating CD27+CD38++ plasmablasts and secreting IgG. By the combination of linkage analysis and whole exome sequencing, we identified two novel mutations in the linkage region, one of them in a protein involved in the immune response. The segregation of this mutation with the disease phenotype in the family was verified by Sanger Sequencing. Multiple myeloma cells did not survive the overexpression of the mutated gene while they tolerated the wild type protein. Overexpression of the mutant variant in other cells like B cells, T cells, monocytes and Hek293T cells did not affect their survival, indicating that the detrimental effects of this mutant are restricted to plasma cells. The underlying pathomechanism might reveal novel insights into plasma cell homeostasis and support the development of therapeutic strategies to treat CVID patients with an infection-only phenotype. Keywords: immunodeficiency, Clinical Immunology, B cells, Plasma Cells, hypogammaglobulinemia, Mutation Conference: IMMUNOCOLOMBIA2015 - 11th Congress of the Latin American Association of Immunology - 10o. Congreso de la Asociación Colombiana de Alergia, Asma e Inmunología, Medellin, Colombia, 13 Oct - 16 Oct, 2015. Presentation Type: Oral Presentation Topic: Immunodeficiencies Citation: Schubert D, Kemming J, Hassdenteufel S, Klein M, Kühn J, Fliegauf M, Winzer S, Schäffer A, Puck J, Hostoffer R, Köttgen A, Rizzi M, Eibel H, Zimmermann R and Grimbacher B (2015). Characterization of a novel genetic defect causing plasma cell deficiency. Front. Immunol. Conference Abstract: IMMUNOCOLOMBIA2015 - 11th Congress of the Latin American Association of Immunology - 10o. Congreso de la Asociación Colombiana de Alergia, Asma e Inmunología. doi: 10.3389/conf.fimmu.2015.05.00350 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 11 May 2015; Published Online: 15 Sep 2015. * Correspondence: Ms. Desirée Schubert, Center for Chronic Immunodeficiency, University Medical Center Freiburg, Freibug, Germany, desiree.schubert@uniklinik-freiburg.de Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Desirée Schubert Janine Kemming Sarah Hassdenteufel Marie-Christine Klein Johannes Kühn Manfred Fliegauf Sandra Winzer Alejandro Schäffer Jennifer Puck Robert Hostoffer Anna Köttgen Marta Rizzi Hermann Eibel Richard Zimmermann Bodo Grimbacher Google Desirée Schubert Janine Kemming Sarah Hassdenteufel Marie-Christine Klein Johannes Kühn Manfred Fliegauf Sandra Winzer Alejandro Schäffer Jennifer Puck Robert Hostoffer Anna Köttgen Marta Rizzi Hermann Eibel Richard Zimmermann Bodo Grimbacher Google Scholar Desirée Schubert Janine Kemming Sarah Hassdenteufel Marie-Christine Klein Johannes Kühn Manfred Fliegauf Sandra Winzer Alejandro Schäffer Jennifer Puck Robert Hostoffer Anna Köttgen Marta Rizzi Hermann Eibel Richard Zimmermann Bodo Grimbacher PubMed Desirée Schubert Janine Kemming Sarah Hassdenteufel Marie-Christine Klein Johannes Kühn Manfred Fliegauf Sandra Winzer Alejandro Schäffer Jennifer Puck Robert Hostoffer Anna Köttgen Marta Rizzi Hermann Eibel Richard Zimmermann Bodo Grimbacher Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. 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