Event Abstract

Back to Event

Altered B cell development and fuctions in Adenosine Deaminase deficient patients

Immacolata Brigida1*, Aisha V. Sauer1, Francesca Ferrua2, Stefania Giannelli1, Samantha Scaramuzza1, Maria Pia Cicalese2, Miriam Casiraghi2, Elisabetta Traggiai3, Mirjam Van Der Burg4 and Alessandro Aiuti1, 5
  • 1 San Raffaele Ospital, HSR-TIGET, department of regenerative medicine stem cells and gene therapy, Italy
  • 2 San Raffaele Scientific Institute, Milan, Pediatric Immunohematology and Bone Marrow Transplantation Unit, Italy
  • 3 Novartis Institute for Research in Biomedicine, Switzerland
  • 4 Erasmus MC, University Medical Center, Department of Immunology, Netherlands
  • 5 Tor Vergata University, Department of Systems Medicine, Italy

Adenosine deaminase (ADA) deficiency causes severe cellular and humoral immune deficiency and dysregulation due to metabolic toxicity. Alterations in B cell development and function have been poorly studied in these patients. Enzyme replacement therapy (ERT) and hematopoietic stem cell gene therapy (GT) are therapeutic options in patients lacking a suitable bone marrow transplant donor. We studied bone marrow (BM) of ADA-deficient patients and investigate the ability of ERT and GT to restore normal B cell differentiation and functions in BM and PB. We found that BM B cells from untreated ADA-deficient patients show an increased proportion of pre-B1 B-cells and a progressive decrease in later stage of maturation. This is in agreement with observation that the strongest selective advantage for ADA-transduced cells is observed at the transition from immature to naïve cells. BM alterations were overcome in patients treated with GT or ERT, but in the latter group immature B cells were expanded. In the periphery, transitional B cells accumulate under ERT and persist long-term, while after GT, transitional B cell frequency progressively normalized. Down regulation of BAFF-R and higher BAFF plasma levels were observed both in ERT and GT patients. B cell proliferative responses after BCR/TLR triggering were severely impaired in ERT patients but improved after GT. Our findings confirm that transfer of ADA gene into autologous hematopoietic stem cells restores B-cell development and functions.

Keywords: Gene Therapy, ADA-SCID, B cells, B cell development, Autoimmunity

Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.

Presentation Type: Abstract

Topic: Translational immunology and immune intervention

Citation: Brigida I, Sauer AV, Ferrua F, Giannelli S, Scaramuzza S, Cicalese M, Casiraghi M, Traggiai E, Van Der Burg M and Aiuti A (2013). Altered B cell development and fuctions in Adenosine Deaminase deficient patients. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00413

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: 09 Apr 2013; Published Online: 22 Aug 2013.

* Correspondence: Dr. Immacolata Brigida, San Raffaele Ospital, HSR-TIGET, department of regenerative medicine stem cells and gene therapy, Milan, Italy, brigida.immacolata@hsr.it