IMMUNOMODULATORY EFFECTS OF DIFFERENT INTRAVENOUS IMMUNOGLOBULIN PREPARATIONS IN CHRONIC LYMPHOCYTIC LEUKEMIA.

COLADO, ANA; ESTEBAN ELIAS; SARAPURA MARTÍNEZ, VALERIA; CORDINI, GREGORIO; MORANDE, PABLO E; BEZARES FERNANDO; GIORDANO, MIRTA; GAMBERALE, ROMINA; BORGE, MERCEDES

Congreso; LXVIII REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INMUNOLOGÍA (SAI); 2020

Hypogammaglobulinemia is the most frequent immune defect in chronic lymphocytic leukemia (CLL). Although CLL patients usually have low serum levels of IgG, IgM and IgA, most standard immunoglobulin(Ig) preparations contain > 95% of IgG. Pentaglobin is an Ig preparation of intravenous application (IVIg) enriched with IgM andIgA, with the potential benefit to restore Ig levels of all isotypes. Because standard IVIg preparations have well-documented immunomodulatory effects, we aimed to evaluate the effect of Pentaglobin(IVIgGMA) and a standard IVIg preparation (IVIgG) on leukemic andT cells from CLL patients.Peripheral blood mononuclear cells from CLL patients were used.T and B cell activation, induced by immobilized anti-CD3 mAb oranti-IgM mAb respectively, was evaluated by flow cytometry (FC).T cell proliferation in response to anti-CD3 mAb or IL-15 was determined by FC using the CFSE dilution assay. We also evaluated byFC the effect of IVIg preparations on T and B cell apoptosis induced by the BCL-2 inhibitor used for CLL treatment, venetoclax. Experiments were done in presence of IVIgG, IVIgGMA or HSA (ct).We found that IVIgG impaired CD25, CD69 and PD-1 expression(n=9, p<0.05) on activated T cells, while IVIgGMA did not. Bothpreparations decreased T cell proliferation in response to TCR/CD3 stimulation (n=11, p<0.05), whereas only IVIgG, impaired proliferation induced by IL-15 (n=15, p<0.05). Regarding leukemic B cell activation, CD69 and CD86 (n=15, p<0.05) expression on activatedB cells was similarly decreased by both preparations. Finally, IVIg-GMA but not IVIgG, decreased venetoclax-induced T cell apoptosis(n=9, p<0.05) without impairing venetoclax-induced leukemic cells apoptosis.Our results add new data on the effects of different preparations ofIVIg in CLL and show that the IVIgGMA preparation not only impairs leukemic cell activation, but also has a particular profile of immunomodulatory effects on T cells that deserves further investigation.