Emergence of long-lived autoreactive plasma cells in the spleen of primary warm auto-immune hemolytic anemia patients treated with rituximab. (August 2015)

• Record Type: Journal Article
• Authors: Mahévas, Matthieu; Michel, Marc; Vingert, Benoit; Moroch, Julien; Boutboul, David; Audia, Sylvain; Cagnard, Nicolas; Ripa, Julie; Menard, Cédric; Tarte, Karin; Mégret, Jérôme; Le Gallou, Simon; Patin, Pauline; Thai, Lan; Galicier, Lionel; Bonnotte, Bernard; Godeau, Bertrand; Noizat-Pirenne, France; Weill, Jean-Claude; Reynaud, Claude-Agnès
• Is Part Of: Journal of autoimmunity. Volume 62(2015)
• Page Start: 22
• Page End: 30
• Publication Date: 2015-08
• Subjects: Warm autoimmune hemolytic anemia -- B-cell depletion -- Anti-CD20 -- Antibody-secreting cells -- Long-lived plasma cells; wAIHA warm autoimmune hemolytic anemia -- BAFF B-cell activating factor -- ASC antibody-secreting cells -- LLPC long-lived plasma cells -- RTX rituximab -- ITP immune thrombocytopenia -- HD healthy donors -- RBCs red blood cells -- GC germinal-center -- PC plasma cells -- PCA principal component analysis -- PB plasmablasts; Autoimmunity -- Periodicals; Autoimmune diseases -- Periodicals; Autoantibodies -- Periodicals; Autoimmune Diseases -- Periodicals; Auto-immunité -- Périodiques; Maladies auto-immunes -- Périodiques; Electronic journals; 616.978005
• DOI: 10.1016/j.jaut.2015.05.006
• Languages: English
• ISSNs: 0896-8411

Abstract

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. Highlights: Long-term corticoids dampen splenic B-cell responses in wAIHA while splenic autoreactive plasma cells survive the treatment. Splenic plasma cells from rituximab-treated wAIHA patients acquire a long-lived expression profile during the treatment. Increased BAFF level in spleen cultures from rituximab-treated patients may promote the emergence of long-lived plasma cells.