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Vpliv izmenjalne transfuzije v obdobju novorojenčka na imunsko odzivnost in kasnejšo obolevnost
Nosan, Gregor (Author), Avčin, Tadej (Mentor) More about this mentor... This link opens in a new window

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Abstract
Uvod in namen raziskave: Izmenjalna transfuzija krvi (IT) predstavlja pomembno obliko zdravljenja novorojenčkov s hemolitično boleznijo ploda in novorojenčka (HBPN). Ena izmed možnih neželenih transfuzijskih reakcij je s transfuzijo povezana imunomodulacija (STPI), ki preko še ne povsem pojasnjenih mediatorjev in mehanizmov lahko povzroči številne pozitivne in negativne klinične učinke oz. vpliva na kasnejšo obolevnost prejemnikov krvi. Namen raziskave je raziskati vpliv IT v obdobju novorojenčka na imunsko odzivnost in obolevnost oz. ugotoviti, ali IT povzroča STPI. Raziskovalna metodologija: Prvi del raziskave temelji na prospektivni analizi celičnega imunskega odziva, ki smo jo izvedli na kohorti 86 preiskovancev. Od teh je 30 otrok eksperimentalne skupine v starosti nekaj dni zaradi HBPN prejelo IT, 56 zdravih otrok kontrolne skupine pa ni prejelo nobene krvne komponente. V starosti šest tednov in 13 mesecev smo vsem otrokom določili krvno koncentracijo levkocitov, limfocitov in limfocitnih populacij ter serumsko koncentracijo vnetnih in regulatornih citokinov. Drugi del raziskave temelji na retrospektivni analizi specifičnega protitelesnega imunskega odziva na toksoidno cepivo proti davici in tetanusu, serumskih avtoprotiteles in pojavnosti bakterijskih in virusnih okužb, alergijskih, avtoimunskih in rakavih bolezni, ki smo jo izvedli na kohorti 74 preiskovancev. Od teh je 41 otrok eksperimentalne skupine v starosti nekaj dni zaradi HBPN prejelo IT, 33 zdravih otrok kontrolne skupine pa ni prejelo nobene krvne komponente. Rezultati in razprava: Šest tednov po IT so imeli prejemniki IT v primerjavi z zdravimi dojenčki znake imunske izčrpanosti, saj so imeli pomembno nižjo krvno koncentracijo aktiviranih monocitov, aktiviranih celic T pomagalk, regulatornih celic T pomagalk in naivnih ter tranzicijskih limfocitov B. Trinajst mesecev po IT je imunska izčrpanost izzvenela, saj razlike v koncentraciji teh celic ni bilo več, a je razlika med prejemniki IT in zdravimi otroci vseeno ostala, saj so imeli prejemniki IT zmanjšano variabilnost koncentracije imunskih celic in citokinov. Po štirih odmerkih toksoidnega cepiva proti davici in tetanusu so imeli prejemniki IT izrazito močan in pomembno boljši protitelesni imunski proti davičnemu toksoidu. Prejemniki IT so pogosteje obolevali zaradi okužbe z varičela zoster virusom; glede pojavnosti drugih virusnih in bakterijskih okužb, alergijskih, avtoimunskih in rakavih bolezni ter serumskih avtoprotiteles pa se niso razlikovali od zdravih otrok. Zaključki: IT v obdobju novorojenčka povzroča STPI, saj vpliva na delovanje specifičnega celičnega in protitelesnega imunskega odziva. Povzroči kratkoročno in prehodno imunsko izčrpanost, ki izzveni do 13. meseca starosti. Dolgoročno izboljša protitelesni imunski odziv na toksoidno cepivo proti davici in vpliva na pojavnost okužbe z varičela zoster virusom. Možen mehanizem nastanka STPI bi bila lahko masivna antigenska obremenitev, ki kratkoročno povzroči prehodno imunsko izčrpanost, dolgoročno pa pospešeno, a slabše uglašeno zorenje imunskega sistema. Protitelesni imunski odziv na cepljenje s toksoidnim cepivom proti davici in tetanusu je pri prejemnikih IT vsaj primerljiv z učinkovitostjo cepiva pri zdravih otrocih, zato naj bodo prejemniki IT s tema dvema cepivoma cepljeni po uradnemu cepilnemu programu za zdrave otroke.

Language:Slovenian
Keywords:izmenjalna transfuzija, novorojenček, imunomodulacija, celični imunski odziv, protitelesni imunski odziv, imunogenost cepiv, avtoimunost
Work type:Doctoral dissertation (mb31)
Organization:MF - Faculty of Medicine
Year:2020
Views:201
Downloads:70
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Secondary language

Language:English
Title:Effect of exchange transfusion in neonatal period on immune response and morbidity
Abstract:
Introduction and objective: Exchange transfusion (ET) is an important treatment method of newborns with hemolytic disease of the fetus and newborn (HDFN). One of the possible adverse effects of transfusion is transfusion-related immunomodulation (TRIM), which can through still unexplained mediators and mechanisms lead to a number of positive and negative clinical outcomes and affects the subsequent morbidity of blood recipients. The objective of the study is to investigate the impact of ET in the neonatal period on immune response and morbidity and to determine whether ET triggers TRIM. Methods: The first part of the study is a prospective cohort analysis of the cellular immune response of 86 subjects. Thirty children of the experimental group received ET due to HDFN at the age of a few days and 56 healthy children in the control group did not receive any blood component. Blood concentrations of leukocytes, lymphocytes, lymphocyte populations and serum concentrations of inflammatory and regulatory cytokines were determined in all children at the age of six weeks and 13 months. The second part of the study is a retrospective cohort analysis of the specific humoral immune response to toxoid diphtheria and tetanus vaccine, serum autoantibodies and the incidence of bacterial and viral infections, allergic, autoimmune and cancer diseases of 74 subjects. Forty-one children of the experimental group received ET due to HDFN at the age of a few days and 33 healthy children in the control group did not receive any blood component. Results and discussion: At the age of six weeks ET recipients presented with signs of immune exhaustion as they had significantly lower blood concentrations of activated monocytes, activated helper T cells, regulatory helper T cells, naive and transitional B lymphocytes compared to healthy infants. Thirteen months after ET immune exhaustion disappeared as the difference in the concentration of these cells was no longer present, but the difference between ET recipients and healthy children remained as ET recipients exhibited reduced variability of immune cells and cytokines concentration. After four doses of diphtheria and tetanus toxoid vaccine ET recipients showed effective and significantly better humoral immune response to diphtheria toxoid. ET recipients were more likely to develop varicella zoster virus infection; however, the incidence of other viral and bacterial infections, allergic, autoimmune, cancerous diseases and serum autoantibodies did not differ from healthy children. Conclusions: ET in the neonatal period triggers TRIM as it affects specific cellular and humoral immune response. It causes short-term and transient immune exhaustion that resolves by 13 months of age. It improves the long-term humoral immune response to diphtheria toxoid vaccine and affects the incidence of varicella zoster virus infection. A possible mechanism of TRIM development could be a massive antigenic load, which in short term causes transient immune exhaustion and in long term an accelerated but less attuned maturation of the immune system. The humoral immune response to diphtheria and tetanus toxoid vaccine in ET recipients is at least comparable to the efficacy of the vaccine in healthy children, so ET recipients should be vaccinated with these two vaccines according to the official immunization schedule for healthy children.

Keywords:exchange transfusion, newborn, immunomodulation, cellular immune response, humoral immune response, vaccine immunogenicity, autoimmunity

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