Serološke, molekularne i kliničke osobine aloimune neonatalne neutropenije

doctoral thesis

• Title (english): Serological, molecular and clinical characteristics of alloimmune neonatal neutropenia
• Author: Maja Tomičić; MBZ: 206326
• Mentor: Vesna Brkljačić-Kerhin (mentor)
• Committee member: nije dostupno (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; Zagreb
• Defense date and country: 2011-05-04, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences
• Universal decimal classification (UDC): 61 - Medical sciences

Abstract

Aloimuna neonatalna neutropenija (ANN) rezultat je imunizacije majke tijekom trudnoće na neutrofilne antigene „čeda“ naslijeđene od oca. Iako je ANN rijetka bolest, teški oblici povezani s bakterijskim infekcijama i sepsom koji mogu imati smrtni ishod nalažu ranu dijagnostiku i liječenje ove bolesti. Prema podacima iz literature procjenjuje se da je učestalost ANN manje od 1 slučaj na 1000 živorođene djece, a teških oblika ANN 1 slučaj na 6000 živorođene djece. U Republici Hrvatskoj (RH) godišnje bilježimo oko 1-2 zahtjeva za serološkim ispitivanjem aloimune neonatalne neutropenije. Obzirom na oko 45 000 živorođene djece u Hrvatskoj godišnje uočava se da je učestalost ANN značajno niža od očekivane. Cilj ovoga istraživanja bio je procijeniti stvarnu učestalost bolesti u RH, analizirati kliničko-laboratorijske podatke i serološke i molekularne osobine ANN za 23 novorođenčeta za koje je učinjeno laboratorijsko ispitivanje ANN u RH u razdoblju od 1998. do 2008. godine. Analiza retrospektivno prikupljenih podataka za razdoblje od 1998. do 2006. godine pokazuje da je učestalost serološki potvrđene ANN u RH 1 slučaj na 38099 živorođene djece, deseterostruko niža od navedenih podataka iz literature. U razdoblju od 2007. do 2008. godine u kojem su podaci prikupljeni prospektivno, broj serološki potvrđenih slučajeva ANN bio je dvostruko veći, 1:17323 živorođenih. Rezultati prospektivne pilot studije provedene od 2007. do 2008. godine u Rodilištu Klinike za ginekologiju i porodiljstvo KB SM, pokazuju da sustavno laboratorijsko praćenje broja neutrofila u krvi novorođenčeta i serološko ispitivanje ANN u slučaju izolirane neutropenije, uz učestalost ANN od 1: 2843 živorođene djece, znatno doprinose pravovremenom otkrivanju bolesti. Rezultati ispitivanja potvrđuju hipotezu postavljenu u ovome istražvanju, da anti-HLA I protutijela sama mogu uzrokovati ANN. Dodatno serološko i molekularno ispitivanje anti-HLA I protutijela i antigena opravdano je u slučaju kada je probirno ispitivanje pozitivno, a anti-HNA protutijela nisu dokazana. Primjena osjetljive serološke metode za probirno ispitivanje anti-HLA I protutijela u plazmi majke i novorođenčeta znatno doprinosi konačnoj potvrdi dijagnoze ANN.

Abstract (english)

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.

• Keywords: medicina
• Keywords (english): medicine
• Language: croatian
• URN:NBN: urn:nbn:hr:105:218340
• Study programme: Title: Biomedicine and Health Sciences; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica znanosti, područje biomedicine i zdravstva (doktor/doktorica znanosti, područje biomedicine i zdravstva)
• Type of resource: Text
• Extent: 140 str.
• File origin: Born digital
• Access conditions: Open access
• Created on: 2023-05-05 06:35:50