The functional state of neutrophils (PMN) correlates with severity in children with Hemolytic Uremic Syndrome (HUS).

FERNANDEZ, GC; GOMEZ, S; RAMOS, MV; LANDONI, V; EXENI, R; GRIMOLDI, I; ALDUNCIN, M; ISTURIZ, M; PALERMO, M

Córdoba, Argentina

Congreso; VII Congreso Latinoamericano de Inmunología; 2005

ALAI

It has been suggested that activated PMN could contribute to endothelial damage in HUS, the main cause of acute renal failure in children. We have previously demonstrated that HUS PMN are partially deactivated, as a consequence of a post-activation exhaustion process. Here, we investigated whether the activation state of PMN correlates with the severity of the renal impairment. The functional state of circulating PMN from patients was evaluated during the acute period (AP) of HUS. The expression of several activation markers, PMA-induced reactive oxygen species (ROS) generation and spontaneous apoptosis were evaluated by flow cytometry. Healthy children were included as controls. According to Gianantonio’s criteria patients were classified in Grade 1: mild cases, no anuria; Grade 2: moderate cases, <7 days of anuria; or Grade 3: severe cases, >7 days of anuria. Healthy children (HC) HUS AP Grade 1 HUS AP Grade 2 HUS AP Grade 3 Correlation (Spearman) Absolute number (x109/L) 3.8±0.3 8.7±0.9* 10.4±1.2* 15.3±1.2*§# r=0.6, p=0.001 Mean fluorescence intensity (MFI)    CD16 151.1±16.4 55.0±8.3* 60.8±10.1* 39.8±7.0* No correlation    CD11b 184.0±26.1 124.1±19.2* 80.1±11.2* 62.3±7.9*§ r=-0.37, p=0.01    CD66b 184.6±32.3 156.8±16.5 81.2±15.9*§ 103.3±13.8*§ r=-0.35, p=0.01    MPO 166.7±24.0 160.3±23.0 99.3±17.1§ 96.0±19.3*§ r=-0.51, p=0.01 DHR (MFI DHR) 99.0±10.1 113.6±21.7 123.3±34.0 37.7±17.4*§# r=-0.51, p=0.01 % of apoptotic cells 54.6±3.3 45.7±4.2 41.05±16.5 25.1±2.9*§ r=-0.51, p=0.01 % live cells 40.7±3.1 48.1±3.5 51.1±16.8 67.9±3.0*§ r=0.66, p<0.001 *p<0.05 vs HC; §p<0.05 vs HUS AP Grade 1; #p<0.05 vs HUS AP Grade 2. All of the markers, the production of ROS in response to PMA and the percentage of apoptotic cells were profoundly diminished in the more severe group of HUS children. These results indicate that the evolution of a child with HUS will be worse when a higher PMN count and a lower activation state (which reflects a higher previous activation process) are observed at presentation.