IMMUNOMODULATORY EFFECTS OF DIFFERENT INTRAVENOUS IMMUNOGLOBULIN PREPARATIONS IN CHRONIC LYMPHOCYTIC LEUKEMIA

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

CABA

Congreso; LXVIII Reunion anual de la Sociedad Argentina de Inmunología; 2020

Hypogammaglobulinemia is the most frequent immune defect inchronic lymphocytic leukemia (CLL). Although CLL patients usuallyhave low serum levels of IgG, IgM and IgA, most standard immunoglobulin(Ig) preparations contain > 95% of IgG. Pentaglobin is an Igpreparation of intravenous application (IVIg) enriched with IgM andIgA, with the potential benefit to restore Ig levels of all isotypes. Becausestandard IVIg preparations have well-documented immunomodulatoryeffects, 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 determinedby FC using the CFSE dilution assay. We also evaluated byFC the effect of IVIg preparations on T and B cell apoptosis inducedby the BCL-2 inhibitor used for CLL treatment, venetoclax. Experimentswere 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/CD3stimulation (n=11, p<0.05), whereas only IVIgG, impaired proliferationinduced by IL-15 (n=15, p<0.05). Regarding leukemic B cellactivation, 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 cellsapoptosis.Our results add new data on the effects of different preparations ofIVIg in CLL and show that the IVIgGMA preparation not only impairsleukemic cell activation, but also has a particular profile of immunomodulatoryeffects on T cells that deserves further investigation