Giordano Paola, Cascioli Simona, Lassandro Giuseppe, Marcellini Valentina, Cardinale Fabio, Valente Federica, Locatelli Franco, Carsetti Rita
Division of Hematology, Pediatric Unit, AOU "Policlinico-Giovanni XXIII", University of Bari "Aldo Moro", Bari, Italy.
Immunology and Pharmacotherapy Research Area, Bambino Gesù Children's Hospital IRCCS, Rome, Italy.
Pediatr Res. 2016 Feb;79(2):262-70. doi: 10.1038/pr.2015.211. Epub 2015 Oct 22.
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.
We studied 30 patients with ITP and compared them with age-matched controls.
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.
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.
免疫性血小板减少性紫癜(ITP)的特征是由于免疫介导的破坏导致血小板计数减少,这会增加出血风险。与血小板结合的自身抗体将它们标记为在脾脏中过早破坏。因此,脾切除术常作为对药物治疗耐药的慢性疾病形式的治疗方法。
我们研究了30例ITP患者,并将他们与年龄匹配的对照组进行比较。
我们发现慢性ITP患者的B细胞本质上反应过度,在体内产生的IgG比正常情况下多,在体外产生的浆细胞也比正常情况下多。在正常个体脾切除术后,观察到记忆B细胞显著减少,这与对CpG寡脱氧核苷酸的反应性丧失以及随后无法形成抗体产生细胞有关。在酶联免疫斑点法中,我们比较了3例脾切除术后复发的ITP患者、30例健康对照以及37例因创伤、球形红细胞增多症、地中海贫血、非血液系统肿瘤和其他疾病而接受脾切除术的个体。
我们证实ITP患者的B细胞在体外仍反应过度,并且在脾切除术后形成大量抗体产生细胞。因此,慢性ITP可能与内在的B细胞功能亢进有关,导致产生包括抗血小板抗体在内的多种特异性抗体。