Paola Giordano1, Simona Cascioli2, Giuseppe Lassandro1, Valentina Marcellini2, Fabio Cardinale3, Federica Valente1, Franco Locatelli4,5, Rita Carsetti2,6. 1. Division of Hematology, Pediatric Unit, AOU "Policlinico-Giovanni XXIII", University of Bari "Aldo Moro", Bari, Italy. 2. Immunology and Pharmacotherapy Research Area, Bambino Gesù Children's Hospital IRCCS, Rome, Italy. 3. Division of Pulmonology, Allergy, and Immunology, Pediatric Unit, AOU "Policlinico-Giovanni XXIII", Bari, Italy. 4. Department of Oncohaematology, Bambino Gesù Children's Hospital IRCCS, Rome, Italy. 5. Department of Pediatric Science, University of Pavia, Pavia, Italy. 6. Department of Laboratories and Diagnostic Immunology Unit, Bambino Gesù Children's Hospital IRCCS, Rome, Italy.
Abstract
BACKGROUND: Immune thrombocytopenic purpura (ITP) is characterized by reduced platelet count secondary to immune-mediated destruction, this results in an increased bleeding risk. Autoantibodies binding to platelets tag them for premature destruction in the spleen. For this reason, splenectomy is often performed as treatment of chronic forms of disease that are resistant to pharmacological therapy. METHODS: We studied 30 patients with ITP and compared them with age-matched controls. RESULTS: We show that B cells of patients with chronic ITP are intrinsically hyperreactive, producing more than normal IgG in vivo and plasma cells in vitro. In normal individuals after splenectomy, a significant depletion of memory B cells is observed, associated with loss of reactivity to CpG oligodeoxynucleotide and consequent inability to form antibody-producing cells. In Enzyme-Linked ImmunoSpot Methods, we compared three splenectomized ITP patients relapsing after surgery, 30 healthy controls, and 37 individuals splenectomized for trauma, spherocytosis, thalassemia, nonhematological tumor, and other diseases. CONCLUSIONS: We confirmed that B cells of ITP patients remain hyperreactive in vitro and form high numbers of antibody-producing cells after splenectomy. Thus, chronic ITP may be associated with intrinsic B-cell hyperfunction, leading to the production of antibodies with multiple specificities including that against platelets.
BACKGROUND: Immune thrombocytopenic purpura (ITP) is characterized by reduced platelet count secondary to immune-mediated destruction, this results in an increased bleeding risk. Autoantibodies binding to platelets tag them for premature destruction in the spleen. For this reason, splenectomy is often performed as treatment of chronic forms of disease that are resistant to pharmacological therapy. METHODS: We studied 30 patients with ITP and compared them with age-matched controls. RESULTS: We show that B cells of patients with chronic ITP are intrinsically hyperreactive, producing more than normal IgG in vivo and plasma cells in vitro. In normal individuals after splenectomy, a significant depletion of memory B cells is observed, associated with loss of reactivity to CpG oligodeoxynucleotide and consequent inability to form antibody-producing cells. In Enzyme-Linked ImmunoSpot Methods, we compared three splenectomized ITP patients relapsing after surgery, 30 healthy controls, and 37 individuals splenectomized for trauma, spherocytosis, thalassemia, nonhematological tumor, and other diseases. CONCLUSIONS: We confirmed that B cells of ITP patients remain hyperreactive in vitro and form high numbers of antibody-producing cells after splenectomy. Thus, chronic ITP may be associated with intrinsic B-cell hyperfunction, leading to the production of antibodies with multiple specificities including that against platelets.
Authors: Taketoshi Yoshida; Henrik Mei; Thomas Dörner; Falk Hiepe; Andreas Radbruch; Simon Fillatreau; Bimba F Hoyer Journal: Immunol Rev Date: 2010-09 Impact factor: 12.988
Authors: Francesco Rodeghiero; Roberto Stasi; Terry Gernsheimer; Marc Michel; Drew Provan; Donald M Arnold; James B Bussel; Douglas B Cines; Beng H Chong; Nichola Cooper; Bertrand Godeau; Klaus Lechner; Maria Gabriella Mazzucconi; Robert McMillan; Miguel A Sanz; Paul Imbach; Victor Blanchette; Thomas Kühne; Marco Ruggeri; James N George Journal: Blood Date: 2008-11-12 Impact factor: 22.113
Authors: Bob Olsson; Per-Ola Andersson; Margareta Jernås; Stefan Jacobsson; Björn Carlsson; Lena M S Carlsson; Hans Wadenvik Journal: Nat Med Date: 2003-08-24 Impact factor: 53.440
Authors: Jackie M Helms; Kristin T Ansteatt; Jonathan C Roberts; Sravani Kamatam; Kap Sum Foong; Jo-Mel S Labayog; Michael D Tarantino Journal: J Blood Med Date: 2021-04-06
Authors: Iwona Wojcik; David E Schmidt; David Falck; Gestur Vidarsson; Lisa A de Neef; Minke A E Rab; Bob Meek; Okke de Weerdt; Manfred Wuhrer; C Ellen van der Schoot; Jaap J Zwaginga; Masja de Haas Journal: Sci Rep Date: 2021-12-15 Impact factor: 4.379
Authors: Alexandra Schifferli; Franco Cavalli; Bertrand Godeau; Howard A Liebman; Mike Recher; Paul Imbach; Thomas Kühne Journal: Front Med (Lausanne) Date: 2021-06-24