B-cell hyperfunction in children with immune thrombocytopenic purpura persists after splenectomy.
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.
Division of Hematology, Pediatric Unit, AOU "Policlinico-Giovanni XXIII", University of Bari "Aldo Moro", Bari, Italy.
Paola
P
Giordano
Immunology and Pharmacotherapy Research Area, Bambino Gesù Children's Hospital IRCCS, Rome, Italy.
Simona
S
Cascioli
Division of Hematology, Pediatric Unit, AOU "Policlinico-Giovanni XXIII", University of Bari "Aldo Moro", Bari, Italy.
Giuseppe
G
Lassandro
Immunology and Pharmacotherapy Research Area, Bambino Gesù Children's Hospital IRCCS, Rome, Italy.
Valentina
V
Marcellini
Division of Pulmonology, Allergy, and Immunology, Pediatric Unit, AOU "Policlinico-Giovanni XXIII", Bari, Italy.
Fabio
F
Cardinale
Division of Hematology, Pediatric Unit, AOU "Policlinico-Giovanni XXIII", University of Bari "Aldo Moro", Bari, Italy.
Federica
F
Valente
Department of Oncohaematology, Bambino Gesù Children's Hospital IRCCS, Rome, Italy.|Department of Pediatric Science, University of Pavia, Pavia, Italy.
Franco
F
Locatelli
Immunology and Pharmacotherapy Research Area, Bambino Gesù Children's Hospital IRCCS, Rome, Italy.|Department of Laboratories and Diagnostic Immunology Unit, Bambino Gesù Children's Hospital IRCCS, Rome, Italy.
Rita
R
Carsetti
D000293:Adolescent; D001323:Autoantibodies / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D001792:Blood Platelets / Q000276:immunology*; D016022:Case-Control Studies; D049109:Cell Proliferation; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D007156:Immunologic Memory; D008213:Lymphocyte Activation; D008297:Male; D010950:Plasma Cells / Q000276:immunology*; D010976:Platelet Count; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000097:blood / Q000175:diagnosis / Q000276:immunology / Q000601:surgery*; D012008:Recurrence; D013156:Splenectomy; D016896:Treatment Outcome
D001323:Autoantibodies; D007074:Immunoglobulin G