A véralvadás XIII-as faktora: strukturális és funkcionális vonatkozások, jelentősége különböző kórképekben = Blood coagulation FXIII: structural, functional aspects, its involvement in various pathological conditions

Uj megallapitasokat tettunk a FXIII plazmaban tortenő aktivaciojara, a ket alegyseg (FXIII-A es FXIII-B) egymashoz kapcsolodasanak strukturalis elemeire es a FXIIIa-glutamin szubsztrat kapcsolatra vonatkozoan. Uj modszereket dolgoztunk ki a FXIII aktivitas meresere, a FXIII-A intracellularis detektalasara. Utobbi bevezetesre kerult a leukemiak diagnosztikajaban. Immunoassay-t dolgoztunk ki az a2 plazmin inhibitor ket izoformajanak mennyisegi meghatarozasara. 10 FXIII-A hianyos betegen deritettuk fel a hatterben allo mutaciokat es ezek kovetkezmenyeit a feherje strukturajara-funkciojara. Kiserletesen bizonyitottuk, hogy a plazma FXIII hianya sebgyogyulasi zavart okoz. Kimutattuk, hogy myocardialis infarctuson (MI) atesett nőkben emelkedett a plasma FXIII szintje es az emelkedett FXIII szint 2,5-3,0 szorosra fokozza az MI rizikojat, ami kizarolag nőkon ervenyesul. 16 cikk metaanalizisievel a FXIII-A L34 allel szignifikans vedőhatasat lehetett kimutatni a coronaria betegseg ellen, a polimorfizmus a nagy rizikoju magyar populacioban azonban csak emelkedett fibrinogen szint eseten vedő hatasu. A L/L homozigotak FXIII szintje MI-ben szignifikansan alacsonyabb a vad tipusuakenal. Csontvelő ablacio utan csokken, magas thrombocyta szammal jaro myeloproliferativ betegsegben emelkedik a FXIII szintje. Bronchoalveolaris mosofolyadekban kimutathato az alveolaris macrophagokbol szarmazo FXIII-A, chronicus bronchitisben ennek szintje emelkedik, s esetenkent megjelenik a plazma FXIII is. | New results were reported on the activation of factor XIII (FXIII) in plasma, on the structural elements involved in the association of FXIII subunits (FXIII-A and FXIII-B) and on the interaction of activated FXIII (FXIIIa) with its glutamine substrate. Methods were developed for the determination of FXIII activity and the intracellular detection of FXIII-A by flow cytometry. The latter was introduced in the diagnostics of leukemias. Immunoassay was developed for the determination of the two isoforms of a2 plasmin inhibitor. The mutations causing FXIII-A deficiency were identified in 10 patients and their consequences were explored at the protein level. The involvement of FXIII in would healing was proven. It was shown that in women with the history of myocardial infarction (MI) FXIII level was elevated and elevated FXIII level represented a 2.5-3.0-fold increased risk of MI in women, but not in men. A protective effect of the FXIII-A L34 allele against MI was demonstrated by metaanalysis of 16 articles. In the Hungarian population this protective effect prevailed only at high fibrinogen level. FXIII level was decreased in L/L homozygotes with the history of MI. Bone marrow ablation decreased plasma FXIII level, while myeloproliferative diseases increased it. In the bronchoalveolar lavage fluid FXIII-A derived from alveolar macrophages was detected, in inflammatory bronchoalveolar diseases FXIII-A level increased and occasionally plasma FXIII was also be present.