S cirhózou asociovaná imunitná dysfunkcia (CAID) – príčiny, fenotypy a dôsledky

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Autoři: D. J. Havaj ; L. Skladaný
Působiště autorů: Internal Med Department II, Slovak Medical University, Division of Hepatology, Gastroenterology and Liver Transplantation, FD Roosevelt University Hospital, Banska Bystrica, Slovakia
Vyšlo v časopise: Gastroent Hepatol 2022; 76(2): 101-110
Kategorie: Přehledová práce
doi: https://doi.org/10.48095/ccgh2022101

Souhrn

Termín s cirhózou asociovaná imunitná dysfunkcia predstavuje široké spektrum zmien v lokálnej a systémovej imunitnej odpovedi. CAID je charakterizovaná súčasnou prítomnosťou systémového zápalu a imunitného deficitu, ktorých intenzita prejavu závisí od stupňa pokročilosti ochorenia, predisponujúcich a precipitujúcich faktorov. Kľúčovú úlohu v patogenéze CAID zohráva spojenie črevo–pečeň. Porucha ich vzájomnej súhry, ako aj zmeny v zložení mikrobiómu, vedú k poškodeniu črevnej bariéry a následnej permanentnej antigénnej stimulácii, ktorá vedie k novému prozápalovému nastaveniu imunitného systému. Táto zmena charakterizuje nízkozápalový fenotyp CAID. Opakované zosilnenia mikrobiálnej translokácie a opakované pôsobenie precipitujúceho faktora vedú k vzplanutiu systémového zápalu a prelomeniu imunitnej tolerancie. Výsledkom je dysregulovaná hyperinflamačná imunitná odpoveď, ktorá reprezentuje vysokozápalový fenotyp CAID. Zmena fenotypu je podkladom pre progresiu cirhózy do štádia dekompenzácie. Miera systémového zápalu zodpovedá jednotlivým subtypom dekompenzácie, pričom najvyšší stupeň dosahuje pri ACLF, ktoré reprezentuje fulminantný imunofenotyp CAID. K rozvoju dysfunkcie jednotlivých orgánových systémov prispievajú okrem orgánovo špecifických mechanizmov aj hyperinflamačná imunitná odpoveď, imunopatologické a imunometabolické mechanizmy. Trvajúca dysregulovaná prozápalová odpoveď vedie k postupnému vyčerpaniu imunity a preprogramovaniu vrodených a získaných imunitných buniek. Navodená imunoparalýza je príčinou problémových infekcií a predstavuje indolentný imunofenotyp CAID.

Klíčová slova:

mikrobiom – zápal – s cirhózou asociovaná imunitná dysfunkcia (CAID) – nízkozápalový fenotyp – vysokozápalový fenotyp – systémový zápal – fulminantný imunofenotyp – imunoparalýza – indolentný imunofenotyp – spojenie črevo–pečeň

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