Serološke, molekularne i kliničke osobine aloimune neonatalne neutropenije Serological, molecular and clinical characteristics of alloimmune neonatal neutropenia

摘要

Alloimmune neonatal neutropenia (ANN) is the result of maternal alloimmunization during pregnancy to neutrophil antigens inherited from the father. ANN is rare but potentially life-threatening disorder, especially in case of severe bacterial infections and sepsis and therefore demand early diagnostic and specific treatment of the disease. According to the literature data the incidence of ANN less than one per 1000 live births, and severe forms from one per 6000 live births. Only 1 to 2 requests for serologic testing for suspected ANN against 45 000 live births per year in Croatia indicate the incidence of the disease to be considerably lower than expected. The aim of this study was to estimate a real incidence of the disease in Croatia and to analyse clinical and laboratory data and serological and molecular characteristics of ANN in 23 newborns investigated in the period from year 1998 to 2008 in Croatia. Retrospective data analysis for period from year 1998 to 2006 shows the frequency of serologically proven ANN of 1 case per 38099 life-births which is tenfold lower than expected according to the previous published literature data. In the period of prospective collecting of data from 2007 to 2008 the frequency of serologically proven ANN was twofold higher; 1 case per 17323 life-births. Results of prospective pilot study conducted in Maternity ward of University hospital “Sestre Milosrdnice” in the two years period show the ANN incidence of 1 case per 2843 life-births, pointed out that regular laboratory monitoring of neutrophil blood count in all newborns together with serological investigation of ANN in case of isolated neutropenia in the newborn has positive impact on timely diagnosis of ANN. The results of the present study support the hypothesis that anti-HLA class I antibodies alone can cause ANN. Additional serological and molecular testing of HLA I antibodies and antigens is justified in case of positive serological screening of ANN, and negative anti-HNA antibodies. Introduction of serologic method of high sensitivity for anti-HLA I screening in mother’s and newborn’s plasma considerably contributed to final serological confirmation of ANN diagnosis.