Immunologic effects of rituximab on the human spleen in immune thrombocytopenia

• Published in: Blood Vol. 118; no. 16; pp. 4394 - 4400
• Main Authors: Audia, Sylvain, Samson, Maxime, Guy, Julien, Janikashvili, Nona, Fraszczak, Jennifer, Trad, Malika, Ciudad, Marion, Leguy, Vanessa, Berthier, Sabine, Petrella, Tony, Aho-Glélé, Serge, Martin, Laurent, Maynadié, Marc, Lorcerie, Bernard, Rat, Patrick, Cheynel, Nicolas, Katsanis, Emmanuel, Larmonier, Nicolas, Bonnotte, Bernard
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 20.10.2011; Americain Society of Hematology; American Society of Hematology
• Subjects: Adult; Aged; Antibodies, Monoclonal, Murine-Derived - immunology; Antibodies, Monoclonal, Murine-Derived - therapeutic use; B-Lymphocytes - drug effects; B-Lymphocytes - immunology; Biological and medical sciences; Female; Hematologic and hematopoietic diseases; Hematology; Human health and pathology; Humans; Immunobiology; Immunologic Factors - immunology; Immunologic Factors - therapeutic use; Immunology; Life Sciences; Male; Medical sciences; Middle Aged; Platelet diseases and coagulopathies; Platelets and Thrombopoiesis; Purpura, Thrombocytopenic, Idiopathic - drug therapy; Purpura, Thrombocytopenic, Idiopathic - immunology; Rituximab; Spleen - cytology; Spleen - drug effects; T-Lymphocytes, Regulatory - drug effects; T-Lymphocytes, Regulatory - immunology; Th1 Cells - drug effects; Th1 Cells - immunology; Antineoplastic agent; Human; Spleen; Thrombocytopenia; Platelet; Treatment; Hematology; Immunotherapy; Rituximab; Hemopathy; Monoclonal antibody
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2011-03-344051

Immune thrombocytopenia (ITP) is an autoimmune disease with a complex pathogenesis. As in many B cell–related autoimmune diseases, rituximab (RTX) has been shown to increase platelet counts in some ITP patients. From an immunologic standpoint, the mode of action of RTX and the reasons underlying its limited efficacy have yet to be elucidated. Because splenectomy is a cornerstone treatment of ITP, the immune effect of RTX on this major secondary lymphoid organ was investigated in 18 spleens removed from ITP patients who were treated or not with RTX. Spleens from ITP individuals had follicular hyperplasia consistent with secondary follicles. RTX therapy resulted in complete B-cell depletion in the blood and a significant reduction in splenic B cells, but these patients did not achieve remission. Moreover, whereas the percentage of circulating regulatory T cells (Tregs) was similar to that in controls, splenic Tregs were reduced in ITP patients. Interestingly, the ratio of proinflammatory Th1 cells to suppressive Tregs was increased in the spleens of patients who failed RTX therapy. These results indicate that although B cells are involved in ITP pathogenesis, RTX-induced total B-cell depletion is not correlated with its therapeutic effects, which suggests additional immune-mediated mechanisms of action of this drug.