{"id":1046,"date":"2017-01-30T21:25:52","date_gmt":"2017-01-30T20:25:52","guid":{"rendered":"http:\/\/www.newslab.sk\/2017\/01\/30\/klinicky-vyznam-virusu-epsteina-barrovej\/"},"modified":"2017-10-03T10:09:32","modified_gmt":"2017-10-03T08:09:32","slug":"clinical-significance-of-the-epstein-barr-virus","status":"publish","type":"post","link":"https:\/\/www.newslab.sk\/en\/clinical-significance-of-the-epstein-barr-virus\/","title":{"rendered":"Clinical significance of the Epstein-Barr virus"},"content":{"rendered":"<pre><span style=\"color: #ff0000;\"><strong>*All tables, charts, graphs and pictures that are featured in this article can be found in the .pdf\u00a0\r\nattachment at the end of the paper.<\/strong><\/span><\/pre>\n<p>&nbsp;<\/p>\n<p><strong>V<\/strong><strong>\u00ed<\/strong><strong>r<\/strong><strong>u<\/strong><strong>s Epsteina-Barrovej<\/strong><\/p>\n<p>V\u00edrus Epsteina-Barrovej \u00a0(EBV) patr\u00ed medzi \u00a0\u013eudsk\u00e9 herpetick\u00e9 \u00a0v\u00edrusy (niekedy \u00a0ozna\u010dovan\u00fd \u00a0ako \u013eudsk\u00fd herpesv\u00edrus \u00a04, HHV-4). \u013dudsk\u00fd jedinec je jedin\u00fdm prirodzen\u00fdm \u00a0hostite\u013eom. EBV sa vyskytuje sporadicky alebo v mal\u00fdch epid\u00e9mi\u00e1ch v detsk\u00fdch kolekt\u00edvoch a m\u00e1 relat\u00edvne n\u00edzku kontagiozitu. Napriek tomu \u00a0je zamorenos\u0165 \u00a0popul\u00e1cie \u00a0extr\u00e9mne \u00a0vysok\u00e1. Ide o ubikvit\u00e1rne roz\u0161\u00edren\u00fd v\u00edrus s v\u00fdskytom viac ako 90 % v dospelej popul\u00e1cii. Zv\u00fd\u0161en\u00e1 \u00a0transmisia v\u00edrusu je v d\u00f4sledku inaparentnej formy prim\u00e1rnej EBV infekcie, respekt\u00edve viacer\u00fdch \u00a0reaktiv\u00e1ci\u00ed po\u010das \u00a0\u017eivota hostite\u013ea (1, 2).<\/p>\n<p>EBV je u\u017e nieko\u013eko desa\u0165ro\u010d\u00ed predmetom \u00a0intenz\u00edvneho z\u00e1ujmu odbornej verejnosti na celom svete. Ide o komplexn\u00fd v\u00edrus s onkog\u00e9nnym potenci\u00e1lom, ktor\u00fd sa sp\u00e1ja so \u0161irok\u00fdm spektrom \u00a0klinick\u00fdch prejavov. V snahe n\u00e1js\u0165 nov\u00e9 sp\u00f4soby lie\u010dby ochoren\u00ed asociovan\u00fdch s EBV infekciou sa v laborat\u00f3ri\u00e1ch detailne \u0161tuduj\u00fa biologick\u00e9 a patogenetick\u00e9 vlastnosti tohto a in\u00fdch gamaherpesv\u00edrusov (herpesv\u00edrus Kaposiho sark\u00f3mu, my\u0161ac\u00ed gamaherpesv\u00edrus \u00a068) (1, 2, 3).<\/p>\n<p>&nbsp;<\/p>\n<p><strong>E<\/strong><strong>pi<\/strong><strong>d<\/strong><strong>e<\/strong><strong>m<\/strong><strong>i<\/strong><strong>ol\u00f3gia<\/strong><\/p>\n<p>Prame\u0148om \u00a0n\u00e1kazy je chor\u00fd jedinec alebo bezpr\u00edznakov\u00fd nosi\u010d v\u00edrusu. EBV sa pren\u00e1\u0161a int\u00edmnym kontaktom, najm\u00e4 slinami a krvou, ale je mo\u017en\u00e9 \u00a0infikova\u0165 sa aj krvnou transf\u00faziou, pri transplant\u00e1cii kme\u0148ov\u00fdch krvotvorn\u00fdch buniek, org\u00e1nov, pr\u00edpadne intrauterinne alebo pohlavn\u00fdm stykom (4, 5).<\/p>\n<p>Ochorenie \u00a0vyvolan\u00e9 infekciou EBV nie je preventabiln\u00e9 \u00a0o\u010dkovan\u00edm a nie s\u00fa k dispoz\u00edcii ani in\u00e9 hromadn\u00e9 prevent\u00edvne opatrenia na zabr\u00e1nenie prenosu EBV (4).<\/p>\n<p>&nbsp;<\/p>\n<p><strong>Pr<\/strong><strong>im<\/strong><strong>\u00e1<\/strong><strong>r<\/strong><strong>n<\/strong><strong>a infekcia<\/strong><\/p>\n<p>V\u00edrusom Epsteina-Barrovej sa v\u00e4\u010d\u0161ina popul\u00e1cie nakaz\u00ed u\u017e v rannom detstve, respekt\u00edve v adolescentnom veku. Inkuba\u010dn\u00e1 lehota oby\u010dajne trv\u00e1 4 a\u017e 6 t\u00fd\u017ed\u0148ov. Po infekcii vn\u00edmav\u00e9ho jedinca EB v\u00edrusom cez orofarynge\u00e1lny kompartment doch\u00e1dza \u00a0v bunk\u00e1ch nosohltana, slinn\u00fdch \u017eliaz a lymfatick\u00e9ho tkaniva mandl\u00ed k prvotn\u00e9mu \u00a0pomno\u017eeniu \u00a0EBV. V\u00edrus je potom krvnou cestou diseminovan\u00fd do cel\u00e9ho \u00a0tela, v ktorom v r\u00e1mci lymfatick\u00e9ho tkaniva vstupuje a n\u00e1sledne transformuje najm\u00e4 B-lymfocyty. EBV aktivuje indukciu ich rastov\u00e9ho programu a diferenci\u00e1cie na pam\u00e4\u0165ov\u00e9 B-bunky. Infikovan\u00e9 pam\u00e4\u0165ov\u00e9 \u00a0B-bunky s\u00fa uvo\u013enen\u00e9 do perif\u00e9rnej krvi, v ktorej s\u00fa rozozn\u00e1van\u00e9 a likvidovan\u00e9 najm\u00e4 \u0161pecifick\u00fdmi cytotoxick\u00fdmi T-lymfocytmi. Po\u010det infikovan\u00fdch B-buniek postupne \u00a0kles\u00e1, av\u0161ak nikdy nie s\u00fa eliminovan\u00e9 \u00faplne v\u0161etky. Lytick\u00e1 f\u00e1za EBV infekcie postupne \u00a0prech\u00e1dza do latentnej. Po\u010det produkovan\u00fdch antig\u00e9nov EBV je v\u00fdrazne redukovan\u00fd, \u010do u\u013eah\u010duje \u00fanik pred \u00fa\u010dinkami imunitn\u00e9ho syst\u00e9mu. EBV dlhodobo pre\u017e\u00edva v pam\u00e4\u0165ov\u00fdch B-bunk\u00e1ch (mo\u017eno i v epiteli\u00e1lnych bunk\u00e1ch) vo forme epizom\u00e1lnej DNA, no predpoklad\u00e1 sa aj mo\u017enos\u0165 integr\u00e1cie v\u00edrusov\u00e9ho gen\u00f3mu do DNA hostite\u013eskej bunky (4, 6).<\/p>\n<p>&nbsp;<\/p>\n<p><strong>L<\/strong><strong>a<\/strong><strong>t<\/strong><strong>e<\/strong><strong>n<\/strong><strong>t<\/strong><strong>n<\/strong><strong>\u00e1 infekcia a reaktiv\u00e1cia<\/strong><\/p>\n<p>Prvotn\u00e1 ak\u00fatna infekcia prech\u00e1dza do \u0161t\u00e1dia latencie. Ide o \u0161t\u00e1dium perzistentnej v\u00edrusovej infekcie bez akt\u00edvnej produkcie v\u00edrusu. V pr\u00edpade, \u017ee sa infikovan\u00fd leukocyt dostane do prostredia, v ktorom m\u00e1 dostatok sign\u00e1lov na aktiv\u00e1ciu a diferenci\u00e1ciu, latentn\u00e1 infekcia je v \u0148om preru\u0161en\u00e1. V\u00edrus sa za\u010dne mno\u017ei\u0165 a infikova\u0165 \u010fal\u0161ie leukocyty. Tento proces nast\u00e1va napr\u00edklad v prostred\u00ed z\u00e1palu v d\u00f4sledku in\u00e9ho ak\u00fatneho ochorenia (napr\u00edklad chr\u00edpky), in\u00fdch chronick\u00fdch ochoren\u00ed (autoimunitn\u00e9 poruchy, n\u00e1dorov\u00e9 ochorenia, diabetes), u star\u0161\u00edch jedincov alebo pri pod\u00e1van\u00ed ur\u010dit\u00fdch druhov liekov, ke\u010f je \u010dinnos\u0165 imunitn\u00e9ho\u00a0 syst\u00e9mu oslaben\u00e1. Naj\u010dastej\u0161ie k reaktiv\u00e1cii v\u00edrusu doch\u00e1dza v lymfatick\u00fdch uzlin\u00e1ch horn\u00fdch d\u00fdchac\u00edch ciest, odkia\u013e b\u00fdva spravidla vylu\u010dovan\u00fd do sl\u00edn a slizni\u010dn\u00fdch \u00a0sekr\u00e9tov, prostredn\u00edctvom ktor\u00fdch sa v\u00edrus \u0161\u00edri v popul\u00e1cii. K reaktiv\u00e1cii doch\u00e1dza \u00a0i u zdrav\u00fdch \u013eud\u00ed bez sprievodn\u00fdch pr\u00edznakov ochorenia. Reaktiv\u00e1cia v\u00edrusu je neust\u00e1le potl\u00e1\u010dan\u00e1 \u010dinnos\u0165ou imunitn\u00e9ho syst\u00e9mu cielen\u00fdm rozpozn\u00e1van\u00edm a r\u00fdchlou likvi- d\u00e1ciou buniek, v ktor\u00fdch sa EBV za\u010dal mno\u017ei\u0165. Produkt\u00edvna f\u00e1za infekcie sa n\u00e1sledne zastav\u00ed a nastol\u00ed sa rovnov\u00e1ha medzi v\u00edrusom a hostite\u013eom formou latencie. EBV takto perzistuje v svojom hostite\u013eovi do konca \u017eivota (6).<\/p>\n<p>&nbsp;<\/p>\n<p><strong>Kli<\/strong><strong>ni<\/strong><strong>c<\/strong><strong>k<\/strong><strong>\u00e1 manifest\u00e1cia EBV infekcie<\/strong><\/p>\n<p>Prim\u00e1rne EBV infekcie naj\u010dastej\u0161ie prebiehaj\u00fa \u00a0u det\u00ed a mlad\u00fdch dospel\u00fdch. U det\u00ed b\u00fdva priebeh infekcie zv\u00e4\u010d\u0161a inaparentn\u00fd, u adolescentov a mlad\u00fdch dospel\u00fdch m\u00f4\u017ee infekcia prebieha\u0165 bezpr\u00edznakovo, s miernymi ne\u0161pecifick\u00fdmi pr\u00edznakmi alebo naj\u010dastej\u0161ie formou infek\u010dnej mononukle\u00f3zy.<\/p>\n<p>\u0164a\u017ekosti spojen\u00e9 s reaktiv\u00e1ciou EBV alebo chronickou \u00a0perzistentnou infekciou s\u00fa \u010dastej\u0161ie pr\u00edtomn\u00e9 u pacientov s oslabenou imunitnou odpove\u010fou (prim\u00e1rne, sekund\u00e1rne).<\/p>\n<p>&nbsp;<\/p>\n<p><strong>Infek\u010dn\u00e1 mononukle\u00f3za (IM)<\/strong><\/p>\n<p>U mlad\u00fdch dospel\u00fdch je typick\u00fdm prejavom infekcie \u2013 infek\u010dn\u00e1 mononukle\u00f3za, \u00a0pseudomembran\u00f3zna ang\u00edna s kr\u010dnou lymfadenit\u00eddou. V ak\u00fatnom \u0161t\u00e1diu m\u00e1 pacient zv\u00e4\u010d\u0161en\u00e9 lymfatick\u00e9 uzliny, b\u00fdva pozorovan\u00e1 mal\u00e1tnos\u0165, \u00fanava, nevo\u013enos\u0165, hor\u00fa\u010dka, zv\u00e4\u010d\u0161en\u00e1 slezina a pe\u010de\u0148, pr\u00edpadne opuch o\u010dn\u00fdch vie\u010dok, respekt\u00edve celej tv\u00e1re. V krvnom obraze je zv\u00fd\u0161en\u00e9 mno\u017estvo \u00a0leukocytov \u00a0(50 %), pri\u010dom \u00a0minim\u00e1lne 10 % z nich m\u00e1 atypick\u00fd tvar (ve\u013ek\u00e9 CD8+ cytotoxick\u00e9 T-lymfocyty s bazofilnou cytoplazmou a excentricky ulo\u017een\u00fdm \u00a0jadrom) (1). Z\u00e1rove\u0148 b\u00fdvaj\u00fa zv\u00fd\u0161en\u00e9 pe\u010de\u0148ov\u00e9 testy (oby\u010dajne nie viac ako desa\u0165n\u00e1sobok referen\u010dn\u00fdch hodn\u00f4t).<\/p>\n<p>Pri lie\u010dbe antibiotikami pr\u00edznaky neustupuj\u00fa \u00a0a m\u00f4\u017eu sa objavi\u0165 alergick\u00e9 reakcie (prechodn\u00e1 \u00a0hypersenzitivita na penicil\u00ednov\u00e9 deriv\u00e1ty). Ochorenie m\u00f4\u017ee prebieha\u0165 i bez ang\u00edny, len so zduren\u00edm uzl\u00edn alebo ako hor\u00fa\u010dkov\u00e9 ochorenie s n\u00e1padnou splenomeg\u00e1liou. Ak\u00fatna f\u00e1za ochorenia trv\u00e1 v priemere asi 16 dn\u00ed a potom postupne odznieva. V diferenci\u00e1lnej diagnostike je vhodn\u00e9 \u00a0vy\u0161etrenia doplni\u0165 o kultiv\u00e1ciu z v\u00fdteru tonz\u00edl, ASLO a anti-DN-\u00e1zu \u00a0B, vzh\u013eadom na to, \u017ee na tonzilit\u00edde pri IM sa \u010dasto etiologicky podie\u013ea <em>S<\/em><em>t<\/em><em>r<\/em><em>e<\/em><em>p<\/em><em>t<\/em><em>o<\/em><em>c<\/em><em>o<\/em><em>c<\/em><em>c<\/em><em>u<\/em><em>s pyogenes <\/em>(6, 7).<\/p>\n<p>IM b\u00fdva spojen\u00e1 s v\u00fdrazn\u00fdm oslaben\u00edm obranyschopnosti organizmu, najm\u00e4 v oblasti bunkovej imunity. U norm\u00e1lne reaguj\u00facich jedincov je imunosupres\u00edvny vplyv EBV infekcie do\u010dasn\u00fd. Pri klinicky zjavn\u00fdch prejavoch ochorenia b\u00fdva IM sprev\u00e1dzan\u00e1 dlh\u00fdm obdob\u00edm rekonvalescencie (oby\u010dajne nieko\u013eko mesiacov), pre ktor\u00e9 je charakteristick\u00e9 ni\u017e\u0161ia v\u00fdkonnos\u0165 organizmu, zv\u00fd\u0161en\u00e1 \u00fanava, zv\u00fd\u0161en\u00e1 n\u00e1chylnos\u0165 na in\u00e9 infekcie alebo alergick\u00e9 reakcie (7, 8).<\/p>\n<p>Z komplik\u00e1ci\u00ed sa ako najz\u00e1va\u017enej\u0161ou \u00a0jav\u00ed dychov\u00e1 nedostato\u010dnos\u0165 sp\u00f4soben\u00e1 z\u00fa\u017een\u00edm d\u00fdchac\u00edch ciest zduren\u00fdm lymfatick\u00fdm tkanivom. Ve\u013emi \u010dast\u00e9 je po\u0161kodenie pe\u010dene a asi u 5 % chor\u00fdch sa vyskytuje zv\u00fd\u0161en\u00e1 bilirubin\u00e9mia (\u010dastej\u0161ie u dospel\u00fdch jedincov). Vz\u00e1cnej\u0161\u00edmi komplik\u00e1ciami s\u00fa: myokardit\u00edda, prechodn\u00fd \u00a0\u00fatlm krvotvorby, hemolytick\u00e1 an\u00e9mia, rupt\u00fara sleziny, neurologick\u00e9 \u00a0komplik\u00e1cie (encefalit\u00edda, polyradikuloneurit\u00edda), o\u010dn\u00e9 komplik\u00e1cie, a to i bez klinick\u00e9ho obrazu IM (7).<\/p>\n<p>V\u00fdznamnou skuto\u010dnos\u0165ou pre prax je, \u017ee pacienti po prekonan\u00ed ak\u00fatnej EBV infekcie s\u00fa do\u010dasne imunokompromitovan\u00ed, hlavne v oblasti bunkovej imunity, v d\u00f4sledku \u010doho:<\/p>\n<ul>\n<li>s\u00fa n\u00e1chylnej\u0161\u00ed hlavne na v\u00edrusov\u00e9 a mykotick\u00e9 infekcie,<\/li>\n<li>u pacientov s precitlivenos\u0165ou v\u010dasn\u00e9ho typu m\u00f4\u017ee by\u0165 myln\u00e1 negativita ko\u017en\u00fdch testov.<\/li>\n<\/ul>\n<p>Boli op\u00edsan\u00e9 \u00a0sporadick\u00e9 pr\u00edpady pacientov, u ktor\u00fdch sa pr\u00edznaky IM vr\u00e1tili pred koncom ak\u00fatneho ochorenia. Tak\u00e9to rekurentn\u00e9 \u00a0alebo\u00a0\u201esekund\u00e1rne\u201c pr\u00edpady IM po odznen\u00ed ak\u00fatneho \u0161t\u00e1dia sa v\u0161ak len ve\u013emi zriedka podar\u00ed dokumentova\u0165 \u00a0laborat\u00f3rnymi testami sved\u010diacimi \u00a0o akt\u00edvnej EBV infekcii.<\/p>\n<p>&nbsp;<\/p>\n<p><strong>Chronick\u00e1 akt\u00edvna infekcia<\/strong><\/p>\n<p>U niektor\u00fdch jedincov sa po odznen\u00ed \u00a0ak\u00fatneho \u00a0\u0161t\u00e1dia EBV infekcie postupne \u00a0rozv\u00edja chronick\u00e1 akt\u00edvna EBV infekcia (4, 6, 9, 10, 11). Ide o vz\u00e1cnu poruchu, ktor\u00e1 je definovan\u00e1 tromi charakteristikami:<\/p>\n<ul>\n<li>klinick\u00e9 pr\u00edznaky IM (subfebrility, \u00fanava, faryngit\u00edda, lymfadenopatia, bolesti k\u013abov) pr\u00edtomn\u00e9 \u00a0viac ako 6 mesiacov, spojen\u00e9 s pozitivitou protil\u00e1tok proti antig\u00e9nom \u00a0lytickej f\u00e1zy,<\/li>\n<li>histologick\u00fd d\u00f4kaz org\u00e1nov\u00e9ho postihnutia (interstici\u00e1lna pneum\u00f3nia, hepatit\u00edda, hypopl\u00e1zia kostnej drene),<\/li>\n<li>histologick\u00fd n\u00e1lez EBV DNA v tkaniv\u00e1ch.<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n<p><strong>Chronick\u00fd \u00fanavov\u00fd syndr\u00f3m (CFS \u2013 chronic fatigue syndrome)<\/strong><\/p>\n<p>V minulosti sa chronick\u00e1 EBV infekcia zva\u017eovala ako jedna z mo\u017en\u00fdch pr\u00ed\u010din CFS. V s\u00fa\u010dasnosti sa odborn\u00edci \u00a0prikl\u00e1\u0148aj\u00fa k n\u00e1zoru, \u017ee ide o komplexn\u00fa poruchu organizmu vyvolan\u00fa pravdepodobne viacer\u00fdmi sp\u00fa\u0161\u0165a\u010dmi (infekcie, porucha imunitn\u00e9ho syst\u00e9mu, nutri\u010dn\u00e9 deficiencie, stres, n\u00edzky krvn\u00fd tlak). Diagnostika CFS je n\u00e1ro\u010dn\u00e1. \u00danava b\u00fdva \u010dast\u00fdm pr\u00edznakom viacer\u00fdch ochoren\u00ed, preto je potrebn\u00e9 v r\u00e1mci diferenci\u00e1lnej diagnostiky vykona\u0165 \u0161irok\u00fa \u0161k\u00e1lu testov, aby sa zistila prav\u00e1 pr\u00ed\u010dina zdravotn\u00fdch \u0165a\u017ekost\u00ed. Probl\u00e9mom m\u00f4\u017ee by\u0165 interpret\u00e1cia vysok\u00fdch hlad\u00edn protil\u00e1tok proti EBV a in\u00fdm ubikvit\u00e1rnym infek\u010dn\u00fdm patog\u00e9nnym mikroorganizmom, ktor\u00e9 s\u00favisia s celkovou aktiv\u00e1ciou imunitn\u00e9ho syst\u00e9mu charakteristickou pre CFS. \u010cast\u00e1 reaktiv\u00e1cia EBV a \u010fal\u0161\u00edch latentn\u00fdch v\u00edrusov je pravdepodobne ne\u017eiaducou z\u00e1\u0165a\u017eou, ktor\u00e1 m\u00f4\u017ee z\u00e1kladn\u00e9 ochorenie \u00a0zhor\u0161ova\u0165. Jedin\u00e1 mo\u017enos\u0165, ako tomu zabr\u00e1ni\u0165, je snaha o obnovenie rovnov\u00e1hy imunitn\u00e9ho syst\u00e9mu, ku ktorej pri CFS samovo\u013ene nedoch\u00e1dza \u00a0(6, 9, 12).<\/p>\n<p>&nbsp;<\/p>\n<p><strong>EBV a autoimunitn\u00e9 choroby<\/strong><\/p>\n<p>Autoimunitn\u00e9 \u00a0ochorenia tvoria ve\u013ek\u00fa skupinu chor\u00f4b, pri ktor\u00fdch je pr\u00ed\u010dinou patologick\u00e9ho procesu autoreaktivita imunitn\u00e9ho \u00a0syst\u00e9mu proti\u00a0vlastn\u00fdm tkaniv\u00e1m organizmu. Pr\u00ed\u010dina vzniku t\u00fdchto \u00a0chor\u00f4b \u00a0je doteraz neobjasnen\u00e1, av\u0161ak predpoklad\u00e1 \u00a0sa, \u017ee genetick\u00e9 predispoz\u00edcie a vplyvy vonkaj\u0161ieho prostredia sa m\u00f4\u017eu spolupodie\u013ea\u0165 na incidencii a rozvoji t\u00fdchto ochoren\u00ed. EBV infekcia sa pova\u017euje za jeden z mnoh\u00fdch mo\u017en\u00fdch sp\u00fa\u0161\u0165a\u010dov autoimunitn\u00e9ho procesu. EBV vyvol\u00e1va perzistentn\u00fa \u00a0infekciu s \u00fasporn\u00fdm programom latencie v pam\u00e4\u0165ov\u00fdch B-bunk\u00e1ch, \u010do umo\u017e\u0148uje vyhn\u00fa\u0165 sa \u00fa\u010dinkom imunitn\u00e9mu doh\u013eadu. V\u00edrus produkuje viacer\u00e9 imunomodula\u010dn\u00e9 prote\u00edny a m\u00e1 k dispoz\u00edcii aj in\u00e9 mechanizmy, ktor\u00e9 m\u00f4\u017eu za ur\u010dit\u00fdch podmienok \u00a0vies\u0165 k chronickej aktiv\u00e1cii imunitn\u00e9ho \u00a0syst\u00e9mu, \u010dast\u00fdm reaktiv\u00e1ci\u00e1m EBV a tvorbe polyreakt\u00edvnych protil\u00e1tok. Tieto procesy sa javia ako kritick\u00e9 pre navodenie r\u00f4znych imunopatologick\u00fdch \u00a0stavov (reumatoidn\u00e1 \u00a0artrit\u00edda, lupus erythematosus, Crohnova choroba, roztr\u00fasen\u00e1 skler\u00f3za, proliferat\u00edvna lymfohistiocyt\u00f3za, hemofagocyt\u00e1rny syndr\u00f3m), najm\u00e4 u os\u00f4b s funk\u010dnou poruchou bunkovej zlo\u017eky imunity. Navy\u0161e, pri lie\u010dbe t\u00fdchto ochoren\u00ed m\u00f4\u017eu pod\u00e1van\u00e9 imunosupres\u00edvne \u00a0l\u00e1tky ovplyvni\u0165 \u00fa\u010dinnos\u0165 imunitn\u00e9ho dozoru nad latentnou infekciou, v tom pr\u00edpade m\u00f4\u017ee by\u0165 i reaktiv\u00e1cia v\u00edrusu spojen\u00e1 s pr\u00edznakmi ochorenia. U pacientov b\u00fdvaj\u00fa pozorovan\u00e9 zv\u00fd\u0161en\u00e9 hladiny protil\u00e1tok proti niektor\u00fdm EB-v\u00edrusov\u00fdm antig\u00e9nom, zn\u00ed\u017een\u00e1 T-bunkov\u00e1 odpove\u010f \u00a0proti EBV a zv\u00fd\u0161en\u00e1 n\u00e1lo\u017e EBV DNA. Pre diagnostiku \u00a0je pr\u00ednosn\u00fd najm\u00e4 priamy d\u00f4kaz v\u00edrusu (6, 13).<\/p>\n<p>&nbsp;<\/p>\n<p><strong>Ochorenia s\u00favisiace s onkog\u00e9nnym potenci\u00e1lom EBV<\/strong><\/p>\n<p>EBV prote\u00edny latencie s\u00fa u\u017e dlh\u0161ie zn\u00e1me pre svoj onkog\u00e9nny potenci\u00e1l. V\u00edrus sa d\u00e1va do s\u00favislosti s viacer\u00fdmi lymfoproliferat\u00edvnymi poruchami, ktor\u00e9 var\u00edruj\u00fa od ben\u00edgnych ochoren\u00ed a\u017e po agres\u00edvne mal\u00edgne neopl\u00e1zie. V s\u00fa\u010dasnosti s\u00fa op\u00edsan\u00e9 tri hlavn\u00e9 (pre hostite\u013ea nepriazniv\u00e9) typy latencie EBV, ktor\u00e9 sa l\u00ed\u0161ia v spektre exprimovan\u00fdch antig\u00e9nov a type vyvolan\u00e9ho ochorenia (\u0161tvrt\u00fd typ latencie je u zdrav\u00fdch os\u00f4b).<\/p>\n<p>Infekcia EB v\u00edrusom sama o sebe nesta\u010d\u00ed, aby vyvolala zhubn\u00e9 ochorenie, \u010dasto sa v\u0161ak d\u00e1va do s\u00favislosti s niektor\u00fdmi druhmi lymf\u00f3mov a neopl\u00e1zi\u00ed (Burkittov lymf\u00f3m endemick\u00fd, Hodgkinov lymf\u00f3m asociovan\u00fd s AIDS, non-Hodgkinov lymf\u00f3m mozgu asociovan\u00fd s AIDS, perif\u00e9rny T-bunkov\u00fd lymf\u00f3m, extranod\u00e1lny NK-\/ T-lymf\u00f3m, PTLD, niektor\u00e9 typy karcin\u00f3mu nosohltana, za\u017e\u00edvacieho traktu a zriedka i karcin\u00f3mu \u00a0prsn\u00edka). Diagnostika EBV v s\u00favislosti s n\u00e1dorov\u00fdmi ochoreniami \u00a0je vo v\u0161eobecnosti m\u00e1lo pr\u00ednosn\u00e1. Pr\u00edtomnos\u0165 \u00a0EBV v n\u00e1dorov\u00fdch bunk\u00e1ch nem\u00e1 v\u00e4\u010d\u0161inou \u017eiadny vplyv na diagn\u00f3zu alebo progn\u00f3zu choroby. V\u00fdnimkou je karcin\u00f3m nosohltana, pri ktorom m\u00f4\u017ee vzostup hladiny IgA proti EA (early antigen) signalizova\u0165 relaps ochorenia \u00a0(1, 2, 4, 6, 14, 15).<\/p>\n<p>&nbsp;<\/p>\n<p><strong>Posttransplanta\u010dn\u00e1 lymfoproliferat\u00edvna choroba (PTLD)<\/strong><\/p>\n<p>Ide o polyklon\u00e1lnu alebo monoklon\u00e1lnu \u00a0prolifer\u00e1ciu lymfoidn\u00e9ho tkaniva, ktor\u00e1 sa vyskytuje po transplant\u00e1ci\u00e1ch sol\u00eddnych org\u00e1nov alebo hematopoetick\u00fdch kme\u0148ov\u00fdch buniek. Incidencia PTLD z\u00e1vis\u00ed od viacer\u00fdch faktorov, ako s\u00fa napr\u00edklad vek pacienta, anti-EBV s\u00e9rostatus donora a recipienta pred transplant\u00e1ciou, typ transplantovan\u00e9ho org\u00e1nu, miera zhody darcu a pr\u00edjemcu v HLA syst\u00e9me, typ a intenzita imunosupresie. Frekvencia PTLD var\u00edruje v rozmedz\u00ed cca 1 \u2013 30 %, hoci pri v\u00fdraznej T-bunkovej depl\u00e9cii m\u00f4\u017ee by\u0165 incidencia \u00a0PTLD e\u0161te vy\u0161\u0161ia. Ochorenie m\u00f4\u017ee by\u0165 spojen\u00e9 s pr\u00edznakmi ako pri IM a\u017e po rozvoj monoklon\u00e1lnych a monomorfn\u00fdch lymf\u00f3mov (4, 14).<\/p>\n<p>&nbsp;<\/p>\n<p><strong>Lymfoproliferat\u00edvny syndr\u00f3m viazan\u00fd na chromoz\u00f3m X<\/strong><\/p>\n<p>Mut\u00e1cia v g\u00e9ne k\u00f3duj\u00facom molekulu SAP (SLAM-associated protein; SLAM \u2013 signaling lymphocyte activation molecule) (1, 4). Ide o vroden\u00e9 ochorenie viazan\u00e9 na X-chromoz\u00f3m, postihuj\u00face chlapcov, ktor\u00ed s\u00fa a\u017e do prv\u00e9ho kontaktu s v\u00edrusom \u00a0EBV zdrav\u00ed. Infekcia EBV m\u00f4\u017ee \u00a0u nich vy\u00fasti\u0165 do troch stavov:<\/p>\n<p>\u2212\u00a0 \u00a0\u0165a\u017ek\u00e1 a\u017e fat\u00e1lna IM (58 %),<\/p>\n<p>\u2212\u00a0 \u00a0lymfoproliferat\u00edvny syndr\u00f3m (30 %),<\/p>\n<p>\u2212\u00a0 \u00a0dysimunoglobulin\u00e9mia \u00a0a\u017e hypogamaglobulin\u00e9mia \u00a0(30 %).<\/p>\n<p>&nbsp;<\/p>\n<p><strong>L<\/strong><strong>a<\/strong><strong>b<\/strong><strong>o<\/strong><strong>ra<\/strong><strong>t\u00f3<\/strong><strong>r<\/strong><strong>n<\/strong><strong>a diagnostika<\/strong><\/p>\n<p>Laborat\u00f3rny d\u00f4kaz u imunokompetentn\u00fdch os\u00f4b sa opiera hlavne o stanovenie \u0161pecifick\u00fdch protil\u00e1tok proti EBV imunos\u00e9rologick\u00fdmi \u00a0met\u00f3dami. Molekul\u00e1rno-biologick\u00e9 met\u00f3dy s\u00fa vhodn\u00e9 predov\u0161etk\u00fdm pre imunosuprimovan\u00fdch pacientov a pri vy\u0161\u0161ie uveden\u00fdch \u00a0komplik\u00e1ci\u00e1ch spojen\u00fdch s akt\u00edvnou EBV infekciou.<\/p>\n<p>V diagnostike infek\u010dnej mononukle\u00f3zy \u00a0sa v men\u0161ej miere vyu\u017e\u00edva kvantitat\u00edvne stanovenie heterofiln\u00fdch protil\u00e1tok. Ich vznik indukuj\u00fa neoantig\u00e9ny v bunkovej membr\u00e1ne \u00a0transformovan\u00fdch B-lymfocytov s EBV. Z metodick\u00e9ho h\u013eadiska ide o Paul-Bunnelovu reakciu (aglutin\u00e1cia s baran\u00edmi erytrocytmi), IM test (aglutin\u00e1cia s konsk\u00fdmi erytrocytmi) a Ericsonov test (OCH test, hemol\u00fdza \u00a0hov\u00e4dz\u00edch \u00a0erytrocytov \u00a0v nadbyt- ku komplementu). Testy s\u00fa ekonomicky nen\u00e1ro\u010dn\u00e9 a pri jednozna\u010dnej pozitivite s\u00fa pr\u00ednosom \u00a0pri stanoven\u00ed diagn\u00f3zy. V tomto pr\u00edpade nie je potrebn\u00fd \u00a0d\u00f4kaz \u0161pecifick\u00fdch \u00a0protil\u00e1tok. Limit\u00e1ciou \u00a0stanovenia heterofiln\u00fdch protil\u00e1tok je fakt, \u017ee nemusia by\u0165 pr\u00edtomn\u00e9 v dostato\u010dnej hladine pri prebiehaj\u00facej \u00a0EBV infekcii, a to nielen u mal\u00fdch \u00a0det\u00ed, ale i adolescentov. Pri diagnostike EBV u dospel\u00fdch \u00a0neb\u00fdvaj\u00fa met\u00f3dou vo\u013eby (7, 8). Pri jednozna\u010dnom klinickom obraze infek\u010dnej mononukle\u00f3zy (v\u00fdnimka deti do 4 rokov) sa vol\u00ed vy\u0161etrenie heterofiln\u00fdch protil\u00e1tok. Pri nejednozna\u010dnom klinickom obraze je potrebn\u00e1 kombin\u00e1cia\u00a0 heterofiln\u00fdch protil\u00e1tok so \u0161pecifick\u00fdmi testami. U pacientov so sekund\u00e1rnou imunodeficienciou sa s\u00e9rologick\u00fd obraz vymyk\u00e1 typick\u00fdm n\u00e1lezom.<\/p>\n<p><em>Stanovenie \u0161pecifick\u00fdch protil\u00e1tok proti EBV <\/em>(met\u00f3dami EIA, CLIA) umo\u017e\u0148uje:<\/p>\n<ol>\n<li>zisti\u0165, \u010di sa vy\u0161etrovan\u00fd pacient\u00a0 u\u017e s infekciou stretol, alebo \u010di je s\u00e9ronegat\u00edvny \u00a0(t. j. vn\u00edmav\u00fd k prim\u00e1rnej infekcii),<\/li>\n<li>ak je s\u00e9ropozit\u00edvny, \u010di ide o akt\u00edvnu infekciu, alebo latentn\u00fa,<\/li>\n<li>v pr\u00edpade akt\u00edvnej infekcie rozl\u00ed\u0161i\u0165 prim\u00e1rnu infekciu od reaktiv\u00e1cie.<\/li>\n<\/ol>\n<p>V r\u00e1mci s\u00e9rologick\u00e9ho vy\u0161etrenia je nutn\u00e9 vykona\u0165 s\u00fabor nieko\u013ek\u00fdch testov, v ktor\u00fdch sa stanovuj\u00fa \u00a0r\u00f4zne druhy protil\u00e1tok proti nieko\u013ek\u00fdm diagnosticky d\u00f4le\u017eit\u00fdm v\u00edrusov\u00fdm antig\u00e9nom. Niektor\u00e9\u00a0 protil\u00e1tky sa tvoria pri prvom kontakte s v\u00edrusom a n\u00e1sledne pretrv\u00e1vaj\u00fa cel\u00fd \u017eivot (tzv. anamnestick\u00e9 \u00a0protil\u00e1tky, napr\u00edklad IgG proti v\u00edrusov\u00e9mu \u00a0kapsidov\u00e9mu antig\u00e9nu \u2013 VCA). In\u00e9 protil\u00e1tky sa tvoria prechodne \u00a0ako odozva na akt\u00edvnu infekciu (prim\u00e1rna \u00a0infekcia alebo \u00a0reaktiv\u00e1cia v\u00edrusu), napr\u00edklad protil\u00e1tky v triede IgM alebo IgA proti VCA, alebo IgG proti v\u010dasn\u00e9mu \u00a0antig\u00e9nu (EA). IgG proti nukle\u00e1rnemu antig\u00e9nu EBV (EBNA 1) sa tvor\u00ed po prim\u00e1rnej infekcii oneskorene (oby\u010dajne v 2. a\u017e 5. mesiaci \u00a0po infekcii, v\u00fdnimo\u010dne a\u017e v 6. a\u017e 12. mesiaci) a pou\u017e\u00edva sa na rozl\u00ed\u0161enie prim\u00e1rnej infekcie od reaktiv\u00e1cie. Pri prim\u00e1rnej infekcii sa spravidla tvoria \u0161pecifick\u00e9 IgM a IgA vo vysokej\u00a0hladine a \u010dasto pretrv\u00e1vaj\u00fa e\u0161te nieko\u013eko t\u00fd\u017ed\u0148ov, respekt\u00edve mesiacov po odznen\u00ed ochorenia. Pri reaktiv\u00e1cii EBV dosahuj\u00fa \u00a0tieto protil\u00e1tky len n\u00edzke hladiny, alebo sa v\u00f4bec netvoria. Naopak, nako\u013eko je reaktiv\u00e1cia v\u00edrusu naj\u010dastej\u0161ie bezpr\u00edznakov\u00e1, m\u00f4\u017eeme \u00a0tieto protil\u00e1tky (najm\u00e4 IgG proti EA\u00a0alebo IgA proti VCA) n\u00e1hodne zachyti\u0165 u zdrav\u00fdch jedincov \u00a0(1, 4, 6, 16).<\/p>\n<p>Reaktiv\u00e1cia mnoh\u00fdch \u00a0herpetick\u00fdch \u00a0v\u00edrusov vr\u00e1tane EBV je be\u017en\u00fdm\u00a0javom v gravidite, v s\u00favislosti s prirodzen\u00fdm oslaben\u00edm bunkovej imunity. Riziko prenosu infekcie na plod je v\u0161ak vo v\u00e4\u010d\u0161ine pr\u00edpadov zanedbate\u013en\u00e9 \u00a0(5).\u00a0Laborat\u00f3ri\u00e1 maj\u00fa mo\u017enos\u0165 pou\u017ei\u0165 r\u00f4zne algoritmy d\u00f4kazu protil\u00e1tok \u00a0proti EBV. Na\u0161e pracovisko stanovuje \u00a0protil\u00e1tky v dvoch modeloch:<\/p>\n<ol>\n<li>protil\u00e1tky proti celoviri\u00f3nov\u00e9mu \u00a0antig\u00e9nov\u00e9mu \u00a0komplexu met\u00f3dou\u00a0ELISA (VCA, EA a EBNA-1 s\u00fa\u010dasne) v triede IgM, IgG, IgA, doplnen\u00e9 o anti-EBNA1 IgG (met\u00f3da CLIA),<\/li>\n<li>protil\u00e1tky proti VCA met\u00f3dou \u00a0CLIA v triede IgM, IgG a anti-EBNA 1 IgG, vo vybran\u00fdch pr\u00edpadoch doplnen\u00e9 o stanovenie protil\u00e1tok triedy IgA\u00a0proti celoviri\u00f3nov\u00e9mu antig\u00e9nov\u00e9mu komplexu (met\u00f3da ELISA).<\/li>\n<\/ol>\n<p>Algoritmus s\u00e9rologick\u00fdch testov v s\u00fa\u010dasnosti v mnoh\u00fdch pr\u00edpadoch umo\u017e\u0148uje laborat\u00f3rnemu pracovn\u00edkovi interpret\u00e1ciu v\u00fdsledku a ur\u010denie \u0161t\u00e1dia infekcie z vy\u0161etrenia jednej vzorky (tabu\u013eka 1).<\/p>\n<p>Ak je potrebn\u00e9 \u00a0pos\u00fadi\u0165 signifikantn\u00e9 zmeny v protil\u00e1tkovej aktivite, vy\u0161etrenie druhej vzorky pri sledovan\u00ed IgM je vhodn\u00e9 minim\u00e1lne o 5 \u2013 10 dn\u00ed, pri sledovan\u00ed IgG o 2 \u2013 3 t\u00fd\u017edne, respekt\u00edve pod\u013ea odpor\u00fa\u010dania laborat\u00f3ria.<\/p>\n<p>V\u00fdsledok s\u00e9rologick\u00e9ho \u00a0vy\u0161etrenia mus\u00ed by\u0165 hodnoten\u00fd v s\u00favislosti s klinick\u00fdm stavom pacienta a s v\u00fdsledkami in\u00fdch laborat\u00f3rnych vy\u0161etren\u00ed. Stanovenie samotn\u00fdch anti-EBV IgM nesta\u010d\u00ed na d\u00f4kaz prim\u00e1rnej \u010di rekurentnej infekcie, mo\u017en\u00e1 je aj heterotypick\u00e1 imunitn\u00e1 odpove\u010f \u00a0vplyvom inej prebiehaj\u00facej \u00a0infekcie (napr\u00edklad CMV, in\u00e9 herpetick\u00e9 \u00a0v\u00edrusy, bor\u00e9lie, v\u00edrus parotit\u00eddy, v\u00edrus rubeoly, v\u00edrus hepatit\u00eddy A) (1, 4, 6, 16).<\/p>\n<p><em>D<\/em><em>\u00f4<\/em><em>k<\/em><em>a<\/em><em>z EBV DNA <\/em>(met\u00f3da PCR). V\u00fdznam priamej DNA diagnostiky spo\u010d\u00edva predov\u0161etk\u00fdm pri diagnostike lymfoproliferat\u00edvnych ochoren\u00ed u imunodeficientn\u00fdch pacientov, chronick\u00fdch \u00a0akt\u00edvnych EBV infekci\u00e1ch, neurologick\u00fdch komplik\u00e1ci\u00e1ch spojen\u00fdch s EB v\u00edrusovou infekciou, monitorovan\u00ed reakcie na lie\u010dbu.<\/p>\n<p>Kvalitat\u00edvne met\u00f3dy detekcie EBV DNA maj\u00fa n\u00edzku predikt\u00edvnu hodnotu, preto sa v s\u00fa\u010dasnosti odpor\u00fa\u010daj\u00fa met\u00f3dy kvantitat\u00edvnej PCR, ktorej v\u00fdsledky s\u00fa pr\u00ednosn\u00e9 v pr\u00edpade, \u017ee s\u00fa interpretovan\u00e9 v s\u00favislosti s v\u00fdsledkami s\u00e9rologick\u00fdch \u00a0vy\u0161etren\u00ed (s v\u00fdnimkou \u00a0\u0165a\u017eko imunosuprimovan\u00fdch pacientov) a s oh\u013eadom na klinick\u00fd stav pacienta.<\/p>\n<p>Pri interpret\u00e1cii \u00a0v\u00fdsledku\u00a0 vy\u0161etrenia \u00a0je potrebn\u00e9 \u00a0ma\u0165 na zreteli prirodzen\u00fa pr\u00edtomnos\u0165 latentn\u00e9ho alebo asymptomaticky vylu\u010dovan\u00e9ho v\u00edrusu v ur\u010dit\u00fdch kompartmentoch. EBV a prechodne \u00a0i CMV, HHV6 alebo HHV7 mo\u017eno citlivou met\u00f3dou \u00a0dok\u00e1za\u0165 i u zdrav\u00fdch asymptomatick\u00fdch jedincov. Na \u00fa\u010dely diagnostiky \u010di monitorovania infekcie je preto nevyhnutn\u00e9 kvantitat\u00edvne stanovenie hlad\u00edn t\u00fdchto v\u00edrusov v krvi, pr\u00edpadne sledovanie ich dynamiky.<\/p>\n<p>\u0160pecifick\u00e9 miesto v priamej diagnostike m\u00e1 d\u00f4kaz\u00a0 EBV v lymfoproliferat\u00edvnych lo\u017eisk\u00e1ch, optim\u00e1lnym vy\u0161etren\u00edm je met\u00f3da \u00a0zalo\u017een\u00e1 na imunohistochemickom d\u00f4kaze v\u00edrusovej latentnej RNA v biopsii pomocou hybridiz\u00e1cie <em>i<\/em><em>n situ <\/em>so zna\u010den\u00fdmi fluorescen\u010dn\u00fdmi sondami. Toto vy\u0161etrenie je dostupn\u00e9 \u00a0len na \u0161pecializovan\u00fdch patologicko-anatomick\u00fdch pracovisk\u00e1ch \u00a0(4, 6, 16, 17, 18, 19).<\/p>\n<p><strong>T<\/strong><strong>e<\/strong><strong>r<\/strong><strong>a<\/strong><strong>pi<\/strong><strong>a a profylaxia<\/strong><\/p>\n<p>Lie\u010dba infek\u010dnej mononukle\u00f3zy je symptomatick\u00e1 a oby\u010dajne zah\u0155\u0148a pod\u00e1vanie \u00a0antipyret\u00edk, analget\u00edk, dodr\u017eiavanie pe\u010de\u0148ovej \u00a0di\u00e9ty, av\u0161ak s dostato\u010dn\u00fdm pr\u00edsunom tekut\u00edn a \u017eiv\u00edn a obmedzenie \u00a0fyzicky n\u00e1ro\u010dn\u00fdch aktiv\u00edt. Antivirotik\u00e1, ktor\u00e9 sa pou\u017e\u00edvaj\u00fa pri lie\u010dbe in\u00fdch herpetick\u00fdch v\u00edrusov (napr\u00edklad acyklovir), p\u00f4sobia \u00a0na EBV iba v ur\u010ditej f\u00e1ze \u017eivotn\u00e9ho \u00a0cyklu, ke\u010f prebieha\u00a0 replik\u00e1cia v\u00edrusovej DNA v infikovanej bunke. Ochorenie sp\u00f4soben\u00e9 \u00a0EBV v\u0161ak nes\u00favis\u00ed len s mno\u017een\u00edm v\u00edrusu, ale aj s mno\u017een\u00edm latentne infikovan\u00fdch buniek, na ktor\u00e9 antivirotik\u00e1 nep\u00f4sobia. Preto nem\u00e1 aplik\u00e1cia antivirot\u00edk pre lie\u010dbu \u00a0z\u00e1sadn\u00fd v\u00fdznam. V pr\u00edpade potreby sa aplikuje symptomatick\u00e1 lie\u010dba a pri bakteri\u00e1lnej superinfekcii antibiotik\u00e1 s v\u00fdnimkou aminopenicil\u00ednov a kotrimoxazolu. Na potla\u010denie anaer\u00f3bnej fl\u00f3ry sa osved\u010dil metronidazol. Pri ob\u0161trukcii horn\u00fdch d\u00fdchac\u00edch \u00a0ciest je nevyhnutn\u00e1 \u00a0intervencia \u00a0kortikosteroidmi \u00a0(4, 6).<\/p>\n<p>Z nov\u0161\u00edch terapeutick\u00fdch postupov sa najm\u00e4 v s\u00favislosti s PTLD sk\u00fa\u0161a pod\u00e1vanie monoklon\u00e1lnych \u00a0protil\u00e1tok (anti-CD19, anti-CD20, anti-CD21 a anti-CD24), intraven\u00f3zneho imunoglobul\u00ednu, EBV-\u0161pecifick\u00fdch cytoto- xick\u00fdch T-lymfocytov a multimod\u00e1lne pr\u00edstupy.<\/p>\n<p>\u010eal\u0161ie \u0161t\u00fadie sa zameriavaj\u00fa na v\u00fdskum nov\u00fdch \u00a0l\u00e1tok vr\u00e1tane lie\u010div ovplyv\u0148uj\u00facich miRNA, EBV vakc\u00edn, \u0161pecifick\u00fdch \u00a0inhib\u00edtorov pre EBV sig- n\u00e1lne molekuly a kombin\u00e1cie indukcie lytickej f\u00e1zy EBV infekcie a anti-EBV chemoterapeut\u00edk (20, 21, 22, 23).<\/p>\n<p>&nbsp;<\/p>\n<p><strong>L<\/strong><strong>it<\/strong><strong>e<\/strong><strong>ra<\/strong><strong>t<\/strong><strong>\u00fa<\/strong><strong>ra<\/strong><\/p>\n<ol>\n<li>Raj\u010d\u00e1ni J, \u010ciampor F. <em>L<\/em><em>e<\/em><em>k\u00e1rska \u00a0<\/em><em>v<\/em><em>i<\/em><em>r<\/em><em>o<\/em><em>l<\/em><em>\u00f3<\/em><em>g<\/em><em>i<\/em><em>a<\/em>. Bratislava: Veda; 2006: 574.<\/li>\n<li>\u010cipkov\u00e1-Jar\u010du\u0161kov\u00e1 J, Mistr\u00edkov\u00e1 J. V\u00edrus Epsteina a Barrovej: jeden \u00a0z najroz\u0161\u00edrenej\u0161\u00edch v\u00edrusov v dospelej \u013eudskej popul\u00e1cii. <em>S<\/em><em>lo<\/em><em>vensk\u00fd lek\u00e1r. <\/em>2013;23(3):55\u201365.<\/li>\n<li>\u010cipkov\u00e1-Jar\u010du\u0161kov\u00e1 J, Chalupkov\u00e1 A, Hrabovsk\u00e1 Z, et al. Biological and pathogenetic characterization of different isolates of murine gammaherpesvirus 68 (MHV-68) in the context of study of human oncogenic gammaherpesviruses. <em>A<\/em><em>c<\/em><em>t<\/em><em>a Virol. <\/em>2013;57(2):105\u201312.<\/li>\n<\/ol>\n<ol start=\"4\">\n<li>Odumade OA, Hogquist KA, Balfour HH Jr. Progress and Problems in Understanding an Managing \u00a0Primary Epstein-Barr Virus Infections. <em>Clin Microbiol <\/em><em>R<\/em><em>e<\/em><em>v<\/em>. 2011;24(1):193\u2013209.<\/li>\n<\/ol>\n<ol start=\"5\">\n<li>Eskild A, Bruu AL, Stray-Pedersen B, et al. Epstein-Barr virus infection \u00a0during \u00a0pregnancy and the risk of adverse pregnancy outcom <em>BJOG: An International Journal of Obstetrics <\/em><em>&amp; Gynaecology. <\/em>2005;112:1620\u20131624.<\/li>\n<li>Roubalov\u00e1 K. <em>C<\/em><em>o je EB-virus a jak\u00fd m\u00e1 vztah k lidsk\u00fdm nemocem <\/em>[online]. Available from:&lt;<a style=\"color: #000000;\" href=\"http:\/\/www.alergieimunita.cz\/2012\/05\/08\/co-je-eb-virus-a-jaky-ma-vztah-k-lidskym-ne-\">http:\/\/www.alergieimunita.cz\/2012\/05\/08\/co-je-eb-virus-a-jaky-ma-vztah-k-lidskym-ne- <\/a>mocem\/;&gt;. Updated \u00a0April 2, 2014.\u00a02010;2(1):e2010022.7.<\/li>\n<li>Hu\u010dkov\u00e1 D. Laborat\u00f3rna diagnostika v\u00edrusov\u00fdch ochoren\u00ed, B6\/1-52. In: Gajdo\u0161\u00edk J, Moro M, eds. <em>D<\/em><em>iagn<\/em><em>ostika <\/em><em>a lie\u010dba infek\u010dn\u00fdch ochoren\u00ed v ambulantnej praxi. <\/em>Raabe; 2009: 1342.<\/li>\n<\/ol>\n<ol start=\"7\">\n<li>Roubalov\u00e1 K. Laboratorn\u00ed diagnostika herpetick\u00fdch vir\u016f. <em>Me<\/em><em>d<\/em><em>. Pro Praxi. <\/em>2010;7(5):241\u2013244.<\/li>\n<li>Pizzigallo E, Racciatti D, Gorgoretti \u00a0V. EBV Chronic \u00a0Infections. <em>Me<\/em><em>di<\/em><em>t J Hemat Infect Dis.<\/em><\/li>\n<\/ol>\n<ol start=\"10\">\n<li>Petrova M, Kamburov V. Epstein-Barr virus: Silent companion or causative agent of chronic liver disease? <em>W<\/em><em>orl<\/em><em>d <\/em><em>J Gastroenterol. <\/em>2010;16(33):4130\u20134134.<\/li>\n<li>Okano M, Gross TG. Acute or chronic life-threatening \u00a0diseases \u00a0associated \u00a0with Epstein-Barr virus infection. <em>A<\/em><em>m J Med Sci. <\/em>2012;343(6):483\u20139.<\/li>\n<\/ol>\n<ol start=\"12\">\n<li><em>C<\/em><em>e<\/em><em>nt<\/em><em>er<\/em><em>s for Disease Control <\/em><em>an<\/em><em>d Prevention: Chronic Fatigue Syndrome (CFS) <\/em>[online]. Availa- ble from: <span style=\"color: #000000;\">&lt;<a style=\"color: #000000;\" href=\"http:\/\/www.cdc.gov\/cfs\/general\/index.html\">http:\/\/www.cdc.gov\/cfs\/general\/index.html.<\/a>&gt;.<\/span><\/li>\n<li>Holck Draborg A, Duus K, Houen G. Epstein-Barr Virus in Systemic Autoimmune Diseases.\u00a0<em>Clin Dev Immunol. <\/em>2013;535738.<\/li>\n<\/ol>\n<ol start=\"14\">\n<li>Ok CY, Li L, Young KH. EBV-driven B-cell lymphoproliferative disorders: from biology, clas- sification and differential diagnosis to clinical management. <em>E<\/em><em>x<\/em><em>p<\/em><em>eri<\/em><em>m<\/em><em>e<\/em><em>n<\/em><em>t<\/em><em>a<\/em><em>l <\/em><em>&amp; Molecular Medi- cine. <\/em>2015;47:e132. doi:10.1038.<\/li>\n<li>\u010ci\u017em\u00e1r A, Predn\u00fd J, Hu\u010dkov\u00e1 D, et al. Infekcia v\u00edrusom Epsteina-Barrovej asociovan\u00e1 s hemofagocytuj\u00facou lymfohistocyt\u00f3zou. <em>K<\/em><em>linick\u00e1 mikrobiologie \u00a0<\/em><em>a infek\u010dn\u00ed l\u00e9ka\u0159stv\u00ed. <\/em>2002;8(4):177\u2013181.<\/li>\n<\/ol>\n<ol start=\"16\">\n<li>Gulley ML, Tang W. Laboratory Assays for Epstein-Barr Virus-Related Diseas <em>J<\/em><em>o<\/em><em>urna<\/em><em>l <\/em><em>o<\/em><em>f\u00a0<\/em><em>M<\/em><em>ole<\/em><em>cular Diagnostics. <\/em>2008;10(4):279\u2013292.<\/li>\n<\/ol>\n<ol start=\"17\">\n<li>Stuhlmann-Laeisz C, Oschlies I, Klapper W. Detection \u00a0of EBV in reactive and neoplastic lymphoproliferations in adults \u2013 when and how? <em>J Hematopathol. <\/em>2014;7:165\u2013170.<\/li>\n<li>Visco C, Falisi E, Young KH, et al. Epstein-Barr virus DNA load in chronic lymphocytic leukemia is an independent predictor of clinical course and survival. <em>O<\/em><em>n<\/em><em>c<\/em><em>otarget. <\/em>2015;6(21):18653\u201318663.<\/li>\n<\/ol>\n<ol start=\"19\">\n<li>Gulley ML, Tang W. Using Epstein-Barr Viral Load Assays to Diagnose, Monitor, and Prevent Posttransplant Lymphoproliferative Disorder. <em>Clin. Microbiol. <\/em>2010;23(2):350\u2013366.<\/li>\n<\/ol>\n<ol start=\"20\">\n<li>Breton CS, Nahimana A, Aubry D, et al. A novel anti-CD19 monoclonal \u00a0antibody (GBR 401) with high killing activity against B cell malignancies. Journal of Hematology &amp; Oncology 2014;7:33. Breton CS, Nahimana \u00a0A, Aubry D, et al. A novel anti-CD19 monoclonal antibody (GBR 401) with high killing activity against B cell malignancies. <em>J<\/em><em>o<\/em><em>urna<\/em><em>l <\/em><em>o<\/em><em>f Hematology &amp; On- cology<\/em>. 2014;7:33. doi:10.1186\/1756-8722-7-33.<\/li>\n<\/ol>\n<ol start=\"21\">\n<li>Kuehnle I, Huls MH, Liu Z, et al. CD20 monoclonal antibody (rituximab) for therapy of Epstein-Barr virus lymphoma after hemopoietic stem-cell transplantation. <em>Bl<\/em><em>oo<\/em><em>d<\/em><em>. \u00a0<\/em>2000;95(4): 1502\u20135.<\/li>\n<\/ol>\n<ol start=\"22\">\n<li>Benkerrou M, Jais JP, Leblond V, et al. Anti-B-Cell Monoclonal Antibody Treatment of Severe Posttransplant B-Lymphoproliferative Disorder: Prognostic Factors and Long-Term Outcom <em>Bl<\/em><em>oo<\/em><em>d<\/em><em>. <\/em>1998;92(9):3137\u201347.<\/li>\n<li>Khanna R, Smith C. Cellular immune \u00a0therapy for viral infections\u00a0 in transplant patients.\u00a0<em>Indian J Med Res<\/em>. 2013;138(5):796\u2013807.<\/li>\n<\/ol>\n","protected":false},"excerpt":{"rendered":"<p>*All tables, charts, graphs and pictures that are featured in this article can be found in the .pdf\u00a0 attachment at the end of the paper. &nbsp; V\u00edrus Epsteina-Barrovej V\u00edrus Epsteina-Barrovej \u00a0(EBV) patr\u00ed medzi \u00a0\u013eudsk\u00e9 herpetick\u00e9 \u00a0v\u00edrusy (niekedy \u00a0ozna\u010dovan\u00fd \u00a0ako \u013eudsk\u00fd herpesv\u00edrus \u00a04, HHV-4). \u013dudsk\u00fd jedinec je jedin\u00fdm prirodzen\u00fdm \u00a0hostite\u013eom. EBV sa vyskytuje sporadicky alebo v<\/p>\n","protected":false},"author":7,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_mi_skip_tracking":false,"footnotes":""},"categories":[292],"tags":[648,645,646,647,564],"class_list":["post-1046","post","type-post","status-publish","format-standard","hentry","category-microbiology","tag-epstein-barr-virus","tag-laboratory-diagnosis","tag-primary-infection","tag-secondary-infection","tag-therapy","typ_clanku-review-article"],"acf":{"abstrakt":"<p>Epstein-Barr virus (EBV) infection is typically manifested as an infectious mononucleosis. The disease is associated with significant impairment of the host immunity, the cellular immunity in particular. The chronically active EBV infection may participate in the formation of a variety of autoimmune processes in individuals with malfunction of cellular immunity (rheumatoid arthritis, proliferative lymphohistiocytosis, hemophagocytic syndrome). Therefore, the differential diagnosis of these clinical problems should include EBV serological tests.<\/p>\n<p>The risk of developing lymphoproliferative disorders and malignant lymphomas (Hodgkin\u2019s disease, lymphomas of B-, T- and NK-cell origin) has been associated with EBV infection in patients with severe immunodeficiency\/immunosuppression. The risk of initializing these processes in immunocompetent individuals is minimal, but exceptionally, the disease may arise in the superposition of several unfavourable factors (environmental influences, genetic predisposition).<\/p>\n<p><strong>Key words:<\/strong> Epstein-Barr virus, laboratory diagnosis, primary infection, secondary infection, therapy<\/p>\n","casopis":[{"ID":991,"post_author":"7","post_date":"2017-02-01 09:43:42","post_date_gmt":"2017-02-01 08:43:42","post_content":"<ul>\r\n \t<li>Pulmonary aspergillosis<\/li>\r\n \t<li>Infections caused by cytomegalovirus \u2013 diagnosis and therapy<\/li>\r\n \t<li>Long-term molecular remission as a precondition for successful pregnancy in patients with chronic myelocyte leukemia<\/li>\r\n \t<li>Chromosome 11 aberrations in a patient with acute myeloid leukemia \u2013 a case study<\/li>\r\n \t<li>New biomarkers in diagnosing IgA nephropathy<\/li>\r\n<\/ul>","post_title":"newslab","post_excerpt":"","post_status":"publish","comment_status":"closed","ping_status":"closed","post_password":"","post_name":"newslab-2016-02","to_ping":"","pinged":"","post_modified":"2017-08-16 21:36:48","post_modified_gmt":"2017-08-16 19:36:48","post_content_filtered":"","post_parent":0,"guid":"http:\/\/www.newslab.sk\/casopis\/newslab-2016-02\/","menu_order":0,"post_type":"casopis","post_mime_type":"","comment_count":"0","filter":"raw"}],"strana":"84","upload_clanok":{"ID":1047,"id":1047,"title":"Newslab_2_2016_Klinick\u00fd v\u00fdznam v\u00edrusu Epsteina-Barrovej_Hu\u010dkov\u00e1_Koll\u00e1rov\u00e1","filename":"Newslab_2_2016_Klinick\u00fd-v\u00fdznam-v\u00edrusu-Epsteina-Barrovej_Hu\u010dkov\u00e1_Koll\u00e1rov\u00e1.pdf","filesize":326579,"url":"https:\/\/www.newslab.sk\/wp-content\/uploads\/2017\/01\/Newslab_2_2016_Klinick\u00fd-v\u00fdznam-v\u00edrusu-Epsteina-Barrovej_Hu\u010dkov\u00e1_Koll\u00e1rov\u00e1.pdf","link":"https:\/\/www.newslab.sk\/en\/clinical-significance-of-the-epstein-barr-virus\/newslab_2_2016_klinicky-vyznam-virusu-epsteina-barrovej_huckova_kollarova\/","alt":"","author":"7","description":"","caption":"","name":"newslab_2_2016_klinicky-vyznam-virusu-epsteina-barrovej_huckova_kollarova","status":"inherit","uploaded_to":1046,"date":"2017-02-01 19:42:23","modified":"2017-02-01 19:42:23","menu_order":0,"mime_type":"application\/pdf","type":"application","subtype":"pdf","icon":"https:\/\/www.newslab.sk\/wp-includes\/images\/media\/document.png"}},"_links":{"self":[{"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/posts\/1046","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/users\/7"}],"replies":[{"embeddable":true,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/comments?post=1046"}],"version-history":[{"count":0,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/posts\/1046\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/media?parent=1046"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/categories?post=1046"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/tags?post=1046"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}