FRANCE PIRENNE

Email: france.pirenne@efs.sante.fr

Team: Transfusion et maladies du globule rouge

Website: http://www.imrb.inserm.fr

Our team is interested in red blood cell disease (mainly sickle cell disease) and transfusion.
Our team is currently an emerging team of the unit U955, of the “Institut de Recherhce Biomédicale” (IMRB) in Henri Mondor Hospital. The team is composed of members of the French Blood Agency (Etablissement Français du Sang), members of the Paris-Est Créteil University and members of the Henri Mondor Hospital in Créteil. The INSERM U779 (director Mike Marden), already member of the GR-Ex will join our team in January 2015 to form a new enlarged team. This new team has been evaluated in January 2014 by the AERES to obtain the INSERM label.

The overall ambition of our team is to combine the expertise of different specialists in RBC disease (from clinical to fundamental aspects), in order to advance in the pathogenesis understanding, to develop new therapeutic approaches and to improve safety of the actual treatments especially transfusion. Transfusion can induce life threatening hemolytic post-transfusion reactions in patients, representing 6% of the causes of death. We are also interested in auto-immune hemolytic anemia (AIHA), as the National Referral Center of autoimmune cytopenia directed by Pr B.Godeau, from the Internal department of medicine, is located in the Hospital and works in close collaboration with the immuno-hématological laboratory of the EFS in H.Mondor.

The axes of the team are developed using the expertise of each member at the DNA, protein and cellular level, with human samples and animal models. Our studies are fundamental but also translational, thanks to the cohorts of sickle cell patients (2000 adults, 700 children), perfectly documented at the clinical, biological and transfusion levels.

The perspectives of this team relies on the following projects :

1/ Pathophysiology of sickle cell disease based mainly on the study of dense red blood cells (DRBCs): we aim to characterize DRBCs, their oxygen transport capacity, their involvement in hemolysis and endothelium damages. In the hemolysis perspective, we aim to define the intra vascular hemolysis based on biological markers (free heme, free hemoglobin), and determine the link with the activation of the alternative pathway of complement. We also work on drugs effects and more specifically, the qualitative HbF distribution in RBC after hydroxycarbamide treatment, or new therapeutic approaches.

2/ Mechanism and side effects of transfusion in SCD: beside epidemiological studies, we aim to go further insight the mechanism of allo immunization using mouse models, and studying immune and immuno-genetic markers in patients. Our studies focus also on mechanism of hemolytic transfusion reaction in SCD, and involvement of variant blood group antigens. We developed translational studies based on the use of new therapeutic approaches in the prevention of allo immunization (mainly Rituximab) and treatment of DHTR (mainly Eculizumab).

3/ Immune regulation and mechanism of red blood cell clearance in AHAI : In parallel with transfusion reaction linked to erythrocyte allo antibodies, we developed a theme based on the hemolytic effect of erythrocyte auto antibodies in AHAI. We have also projects on immune mechanism of AHAI, working mainly on the T cells response against RBC antigens, and on B cells.

4/ Chaperones of RBCs (HSP) and free α-Hb pool: we aim to study the free α Hb pool in SCD, in order to determine if the alpha pool can be used as an index of severity. We plan also to measure this parameter in packed RBCs, and during storage.

Main Publications of the actual members of the team (team U779 not included)

  • Audard V, Moutereau S, Vandemelebrouck G, Habibi A, Khellaf A, Grimbert P, Levy Y, Loric S, Renaud B, Lang P, Godeau B, Galactéros F, Bartolucci P. First evidenceof subclinical renal tubular injury during sickle cell crisis. Orphanet Journal of Rare Diseases, in press, 2014.
  • Silvy M, Tournamille C, Babinet J, Pakdaman S, Cohen S, Chiaroni J, Galactéros F, Bierling P, Bailly P, Noizat-Pirenne F. Red blood cell immunization in sickle cell disease: evidence of a large responder group and a low rate of anti Rh linked to partial Rh phenotype. Haematologica, 2014 Apr 11. [Epub ahead of print]
  • – Vingert B, Tamagne M, Desmarets M, Pakdaman S, Elayeb R, Habibi A, Bernaudin F, Galactéros F, Bierling P, Noizat-Pirenne F, Cohen J. Partial dysfunction of Treg activation in sickle cell disease. 2014. American Journal of Haematology, 89 :261-266.
  • Silvy M, Barrault A, Velliquette RW, Lomas-Francis C, Simon S, Mortelecque R, Chiaroni J, Bierling P, Noizat-Pirenne F, Bailly P, Tournamille C. RHCE*cE734C allele encodes an altered c antigen and a suppressed E antigen not detected with standard reagents. 2013. Transfusion, 53(5):955-961.
  • Yazdanbakhsh K, Ware RE, Noizat-Pirenne F. Red cell alloimmunization in sickle cell disease : pathophysiology, risk factors, and transfusion management.2012. Blood. 120(3):528-37
  • Bartolucci P, Brugnara C, Teixeira-Pinto A, Pissard S, Moradkhani K, Jouault H, Galacteros F. Erythrocyte density in sickle cell syndromes is associated with specific clinical manifestations and hemolysis. 2012. Blood. 120(15):3136-41.
  • de Montalembert, M., M. D. Dumont, C. Heilbronner, V. Brousse, O. Charrara, B. Pellegrino, C. Piguet, V. Soussan, and F. Noizat-Pirenne. Delayed hemolytic transfusion reaction in children with sickle cell disease. 2011. Haematologica 96:801-807.
  • Chadebech, P., M. Michel, D. Janvier, K. Yamada, C. Copie-Bergman, G. Bodivit, A. Bensussan, J. J. Fournie, B. Godeau, P. Bierling, S. Izui, and F. Noizat-Pirenne. IgA-mediated human autoimmune hemolytic anemia as a result of hemagglutination in the spleen, but independent of complement activation and FcalphaRI. 2010. Blood 116:4141-4147.
  • Bartolucci P, El Murr T, Roudot-Thoraval F, Habibi A, Santin A, Renaud B, Noël V, Michel M, Bachir D, Galactéros F, Godeau B. A randomized, controlled clinical trial of ketoprofen for sickle-cell disease vaso-occlusive crises in adults. 2009. Blood, 114(18):3742-3747
  • Tournamille, C., N. Meunier-Costes, B. Costes, J. Martret, A. Barrault, P. Gauthier, F. Galacteros, R. Nzouekou, P. Bierling, and F. Noizat-Pirenne. Partial C antigen in sickle cell disease patients: clinical relevance and prevention of alloimmunization. 2009. Transfusion 50:13-19.
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