Pathogenic mechanisms leading to thrombocytopenia in Systemic Lupus Erythematosus.

LEV PR; PISONI C; MARTA RF; GOETTE NP; COLLADO V; HELLER PG; BARONI PIETTO MC; GLEMBOSTKY AC; FLORES G

Buenos Aires

Congreso; LXII Reunión Anual de la Sociedad Argentina de Investigación Clínica. Reunión Conjunta de Sociedades de Biociencias; 2017

Systemic lupus erythematosus (SLE) is characterized by the production of a wide variety of autoantibodies. In 15-20% of cases, patients develop thrombocytopenia which appears to be autoimmune. This study was aimed at investigating possible causes of low platelet count, including platelet apoptosis and abnormal platelet production. Blood samples from 15 SLE patients (P) (platelet count, median, 92x106/L, range 2-290x106/L) and 10 normal controls were obtained, and platelets as well as plasma samples were separated. Platelets were analyzed for apoptosis parameters and SLE plasma samples were incubated with normal mature megakaryocytes (obtained after 12 day-culture of CD34+ progenitors from normal human cord blood) to assess their effect on proplatelet formation (PPF) (direct count under microscopic observation). Platelet apoptosis was increased in SLE (n=8): phosphatydilserine (PS) exposure (FITC-Anexin-V binding), P 9.3%(0.7-80.2), controls (C) 3.6%(1.9-7.6); loss of mitochondrial inner membrane potential (m) (JC-1), P 26.6%(9.6-71.3), C 12.4%(3.6-18.6); active caspase-3 (FITC-anti active caspase-3 antibody binding), P 3.1%(0.5-34), C 2.7%(1.1-4.6), although not reaching statistical significance (Mann-Whitey test). However, 4/8 patients showed values higher than the normal range, all of them presenting thrombocytopenia. Response to calcium ionophore-induced apoptosis was normal. Basal platelet activation was not observed in our population as evaluated by PAC-1 binding, P 3.4%(0.5-15.8), C 2.8%(1.1-7.4), and P-selectin expression, P 19.9%(11.4-58.2), C 18.7%(5-36.6), indicating that PS exposure is not due to activation but to apoptosis in SLE platelets. PPF was decreased in the presence of SLE plasma samples (n=15), 0.42%(0.14-1.79) compared to C,1.06%(0.51-2.16), p=0.0367 (Mann-Whitney test). In conclusion, peripheral platelet clearance due to platelet apoptosis and inhibition of platelet production could contribute to thrombocytopenia in SLE.