Correlation between Polimorphonuclear Neutrophil Functional State (PMN) and Severity in Patients with the typical form of Hemolytic Uremic Syndrome (HUS)

GABRIELA C. FERNÁNDEZ; VICTORIA RAMOS; VERÓNICA LANDONI; LETICIA BENTANCOR; ROMINA FERNÁNDEZ-BRANDO; RAMÓN EXENI; MARTA ALDUNCÍN; IRENE GRIMOLDI; MARTÍN ISTURIZ; MARINA PALERMO

Melbourne, Australia.

Simposio; VTEC 2006. 6th International Symposium on Shiga Toxin (Verocytotoxin) Producing Escherichia coli Infections; 2006

Activated PMN contribute to endothelial damage in HUS, the main cause of pediatric acute renal failure. We have 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 renal impairment. The expression of activation markers, PMA-induced reactive oxygen species (ROS) generation, and spontaneous apoptosis were evaluated by flow cytometry on circulating PMN from at least 20 HUS patients during the acute period and healthy children (HC, n=12). According to Gianantonio’s criteria, patients were classified in mild, moderate or severe cases (0, <7 or >7 days of anuria, respectively). We found that the absolute number of PMN was significantly increased in all HUS groups compared to HC, and positively correlated with severity (PMNx109/L: HC=3.8±0.3, Mild HUS=8.7±0.9*, Moderate HUS=10.4±1.2*, Severe HUS= 15.3±1.2*§#, r=0.6, p=0.001; *p<0.05 vs. HC, §p<0.05 vs. Mild HUS, #p<0.05 vs. Moderate HUS). Moreover, the expression of different activation markers of PMN, the production of ROS and apoptosis were profoundly diminished in severe cases compared to HC and, with the exception of CD16,  negatively correlated with severity (Mean fluorescence intensity (MFI) of  CD16: HC=151.1±16.4, Mild HUS=55.0±8.3*, Moderate HUS=60.8±10.1*, Severe HUS= 39.8±7.0*; MFI CD11b: HC=184.0±26.1, Mild HUS=124.1±19.2*, Moderate HUS=80.1±11.2*, Severe HUS= 62.3±7.9*§, r=-0.37,p=0.01; MFI CD66b: HC=184.6±32.3, Mild HUS=156.8±16.5, Moderate HUS=81.2±15.9*§, Severe HUS=103.3±13.8*§, r=-0.35,p=0.01; MFI myeloperoxidase:  HC=166.7±24.0, Mild HUS=160.3±23.0, Moderate HUS=99.3±17.1§, Severe HUS= 96.0±19.3*§, r=-0.51,p=0.01; MFI DHR (ROS): HC=99.0±10.1, Mild HUS=113.6±21.7, Moderate HUS=123.3±34.0, Severe HUS= 37.7±17.4*§#, r=-0.50,p=0.02; percentage of apoptosis: HC=54.6±3.3, Mild HUS=45.7±4.2, Moderate HUS=41.05±16.5, Severe HUS= 25.1±2.9*§, r=-0.51,p=0.01; *p<0.05 vs. HC, §p<0.05 vs. Mild HUS, #p<0.05 vs. Moderate HUS). These results point out that a higher PMN count and a more pronounced deactivation state at presentation indicate a worse outcome.