Defective regulatory B-cell compartment in patients with immune thrombocytopenia

• Published in: Blood Vol. 120; no. 16; pp. 3318 - 3325
• Main Authors: Li, Xiaojuan, Zhong, Hui, Bao, Weili, Boulad, Nayla, Evangelista, Jessie, Haider, Muhammad Anis, Bussel, James, Yazdanbakhsh, Karina
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 18-10-2012; Americain Society of Hematology; American Society of Hematology
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Antigen Presentation - immunology; Antigens, CD - metabolism; B-Lymphocytes, Regulatory - immunology; B-Lymphocytes, Regulatory - metabolism; Biological and medical sciences; Blood Platelets - immunology; Case-Control Studies; Cells, Cultured; Female; Flow Cytometry; Hematologic and hematopoietic diseases; Humans; Interleukin-10 - metabolism; Male; Medical sciences; Middle Aged; Monocytes - immunology; Monocytes - metabolism; Platelet diseases and coagulopathies; Platelets and Thrombopoiesis; Purpura, Thrombocytopenic, Idiopathic - immunology; Purpura, Thrombocytopenic, Idiopathic - metabolism; Young Adult; Human; Thrombocytopenia; Cell compartment; Platelet; Hematology; Deficiency; Hemopathy; B-Lymphocyte; Regulatory cell
• ISSN: 0006-4971; 1528-0020; 1528-0020
• DOI: 10.1182/blood-2012-05-432575

B lymphocytes producing antiplatelet autoantibodies play a major role in autoimmune thrombocytopenia (ITP). However, certain B cells, including the human CD19+CD24hiCD38hi subpopulation, possess regulatory functions mediated partly by IL-10. In a cohort of chronic ITP patients with low platelet counts who consisted of patients off treatment, we found a lower frequency of CD19+CD24hiCD38hi in the peripheral compartment of nonsplenectomized patients (P = .03). IL-10 expression after activation was decreased in all ITP circulating CD19+ subpopulations (P < .03), and inhibition of monocyte TNF-α expression by activated B cells was reduced in patients with platelet numbers of < 50 × 109 cells/L (P = .001), indicating that regulatory B cells of patients with ITP are functionally impaired in their ability to dampen monocyte activation. Interestingly, in nonsplenectomized patients whose platelet counts were elevated after treatment with thrombopoietic agents, the frequency of CD19+CD24hiCD38hi B cells was increased compared with those before treatment (P = .02). Altogether, these data indicate a compromised regulatory B-cell com-partment as an additional defect in immune regulation in patients with chronic ITP that may be restored in responders to thrombopoietic treatment.