Expression of Bruton�s tyrosine kinase gene and endoplasmic reticulum stress markers in X-linked agammaglobulinemia

Abstract

Event Abstract Back to Event Expression of Bruton’s tyrosine kinase gene and endoplasmic reticulum stress markers in X-linked agammaglobulinemia Vanessa Ramalho1, Marcelo Teocchi1, Beatriz Abramczuk1, Taís N. Mazzola1 and Maria Marluce Vilela1* 1 State University of Campinas Medical School, Pediatrics, Brazil INTRODUCTION: X-linked agammaglobulinemia (XLA) is characterized by a B lymphocyte differentiation block in the bone marrow, leading to hypogammaglobulinemia with few, or the absence of, peripheral B lymphocytes. Mutations in the BTK gene are responsible for XLA and in most cases lead to low protein expression. Misfolded proteins can trigger stress pathways in the endoplasmic reticulum (ER). METHODS: We evaluated eight male Brazilian patients whose diagnosis was based on recurrent infections, markedly reduced levels of IgM, IgG and IgA, and circulating B cell numbers <2%. BTK mutations were identified by sequencing and the mRNA expression of BTK and ER stress markers was assessed with real-time quantitative PCR (RT-qPCR) technology. RESULTS: We detected four missense mutations, one nonsense mutation, two frameshifts and one splice site defect. Quantitative real-time detection PCR measurements showed a reduced expression of BTK mRNA in patients with mutations that result in a stop codon. However, we found that missense mutations do not affect BTK mRNA expression. XLA patients showed an increased level of XBP-1 mRNA and a reduced expression of HSP90B1 mRNA, which could be a mechanism to revert cellular ER stress. CONCLUSIONS: The quantification of BTK mRNA expression is an interesting tool to identify and differentiate the mutational consequences in XLA patients. It can also contribute to the study of transcripts in other genetic diseases with different types of mutation. Acknowledgements FINANCIAL SUPPORT: FAPESP Fundação de Amparo à Pesquisa do Estado de São Paulo http://www.fapesp.br/and CAPES Coordenação de Aperfeiçoamento de Pessoal de Nível Superior http://www.capes.gov.br/ References Lindvall JM, Blomberg KE, Väliaho J, Vargas L, Heinonen JE, Berglöf A, et al. Bruton's tyrosine kinase: cell biology, sequence conservation, mutation spectrum, siRNA modifications, and expression profiling. Immunol Rev. 2005;203:200-15. Korennykh A, Walter P. Structural basis of the unfolded protein response. Annu Rev Cell Dev Biol. 2012;28:251-77. Futatani T, Miyawaki T, Tsukada S, Hashimoto S, Kunikata T, Arai S, et al. Deficient expression of Bruton's tyrosine kinase in monocytes from X-linked agammaglobulinemia as evaluated by a flow cytometric analysis and its clinical application to carrier detection. Blood 1998; 91:595-602. Keywords: Primary immunodeficiency, B cells deficiency, Agammaglobulinemia, XLA agammaglobulinemia, Unfolded Protein Response Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Adaptive Immunity Citation: Ramalho V, Teocchi M, Abramczuk B, Mazzola TN and Vilela M (2013). Expression of Bruton’s tyrosine kinase gene and endoplasmic reticulum stress markers in X-linked agammaglobulinemia. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00880 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: 21 Jun 2013; Published Online: 22 Aug 2013. * Correspondence: Prof. Maria Marluce Vilela, State University of Campinas Medical School, Pediatrics, Campinas, São Paulo, 13083887, Brazil, marluce@fcm.unicamp.br 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 Vanessa Ramalho Marcelo Teocchi Beatriz Abramczuk Taís N Mazzola Maria Marluce Vilela Google Vanessa Ramalho Marcelo Teocchi Beatriz Abramczuk Taís N Mazzola Maria Marluce Vilela Google Scholar Vanessa Ramalho Marcelo Teocchi Beatriz Abramczuk Taís N Mazzola Maria Marluce Vilela PubMed Vanessa Ramalho Marcelo Teocchi Beatriz Abramczuk Taís N Mazzola Maria Marluce Vilela Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.