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Recent studies suggest that PRF1 A91V genotype is present in the normal population, thus being insufficient per se to cause FHLH, although it may represent a genetic susceptibility factor for immune dysregulation (Zhang et?al, 2007). One of these patients also carried a heterozygous UNC13D R967E mutation. In eight patients and 13 controls, the degranulation of NK cells, through CD107a expression, and IFN�� production after incubation with K562 line cells was evaluated. The percentage of CD107a+CD56+CD3? cells and IFN��+CD56+CD3? lymphocytes http://www.selleckchem.com/products/Rapamycin.html vs. 84.60?��?2.07%, respectively; P? http://www.selleckchem.com/products/MG132.html pathogenesis of HLH under condition of challenge by viral infections or other types http://www.selleck.cn/products/Bleomycin-sulfate.html of environmental stress. In conclusion, the clinical course of paediatric HLH with unknown genetic alteration is more favorable then FHLH, as suggested by later onset, lower prevalence of neurological involvement and better outcome. Given that HLH is a potentially life-threatening condition shared by distinct unrelated clinical entities, the definition of the underlying common pathogenetic mechanism is mandatory to better define the management of such patients and open new therapeutic options. GG, CV, RN, EC, and VG selected the cases, analysed and interpreted the data, and wrote the manuscript. GR, VR and AP performed and reviewed the degranulation and IFN�� production assays and critically revised the manuscript. VP critically revised the manuscript. CD selected the cases and critically revised the manuscript. CP selected the cases, analysed and interpreted the data, reviewed the degranulation and IFN�� production assays and wrote and critically revised the manuscript. The authors declare no conflict of interest. ""Two population-based studies recently identified a high prevalence of unexplained thrombocytopenia, especially in men and older people (Biino et?al, 2011; Santimone et?al, 2011). Moreover, these studies reported a wide variability in the prevalence of thrombocytopenia in different villages.