Emergence of long-lived autoreactive plasma cells in the spleen of primary warm auto-immune hemolytic anemia patients treated with rituximab.

Abstract

Primary warm autoimmune hemolytic anemia (wAIHA) is a rare autoimmune disease in which red blood cells are eliminated by IgG autoantibodies. We analyzed the antibody-secreting cells in the spleen and the peripheral blood of wAIHA patients in various contexts of treatment. Plasmablasts were observed in peripheral blood of newly diagnosed wAIHA patients and, accordingly, active germinal center reactions were present in the spleen of patients receiving short-term corticosteroid therapy. Long-term corticosteroid regimens markedly reduced this response while splenic plasma cells were able to persist, a fraction of them secreting anti-red blood cell IgG in vitro. In wAIHA patients treated by rituximab and who underwent splenectomy because of treatment failure, plasma cells were still present in the spleen, some of them being autoreactive. By using a set of diagnostic genes that allowed us to assess the plasma cell maturation stage, we observed that these cells displayed a long-lived program, differing from the one of plasma cells from healthy donors or from wAIHA patients with various immunosuppressant treatments, and more similar to the one of normal long-lived bone-marrow plasma cells. Interestingly, an increased level of B-cell activating factor (BAFF) was observed in the supernatant of spleen cell cultures from such rituximab-treated wAIHA patients. These results suggest, in line with our previous report on primary immune thrombocytopenia, that the B-cell depletion induced by rituximab promoted a suitable environment for the maturation and survival of auto-immune long-lived plasma cells in the spleen.

• Authors: Matthieu Mahévas, Marc Michel, Benoit Vingert, Julien Moroch, David Boutboul, Sylvain Audia, Nicolas Cagnard, Julie Ripa, Cédric Menard, Karin Tarte, Jérôme Mégret, Simon Le Gallou, Pauline Patin, Lan Thai, Lionel Galicier, Bernard Bonnotte, Bertrand Godeau, France Noizat-Pirenne, Jean-Claude Weill, Claude-Agnès Reynaud
• Journal: Journal of autoimmunity (J Autoimmun) Vol. 62 Pg. 22-30 (Aug 2015) ISSN: 1095-9157 [Electronic] England
• PMID: 26112660 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Ltd. All rights reserved.

Chemical References

• Autoantibodies
• B-Cell Activating Factor
• Immunologic Factors
• Rituximab

Topics

• Adult
• Aged
• Anemia, Hemolytic, Autoimmune (drug therapy, genetics, immunology, surgery)
• Autoantibodies (blood, immunology)
• Autoimmunity
• B-Cell Activating Factor (metabolism)
• B-Lymphocyte Subsets (immunology, metabolism)
• Erythrocytes (immunology)
• Female
• Gene Expression Profiling
• Germinal Center (immunology, metabolism, pathology)
• Humans
• Immunologic Factors (therapeutic use)
• Lymphocyte Count
• Male
• Middle Aged
• Plasma Cells (immunology, metabolism)
• Rituximab (therapeutic use)
• Spleen (immunology, metabolism, pathology)
• Splenectomy
• Young Adult