{"id":1756,"date":"2019-05-09T13:52:26","date_gmt":"2019-05-09T11:52:26","guid":{"rendered":"http:\/\/www.newslab.sk\/2019\/05\/09\/vyznam-a-diagnostika-antifosfolipidovych-protilatok-u-zien-s-poruchami-reprodukcie\/"},"modified":"2019-05-09T13:57:56","modified_gmt":"2019-05-09T11:57:56","slug":"importance-and-diagnostic-of-anti-phospholipid-antibodies-in-women-with-reproductive-disorders","status":"publish","type":"post","link":"https:\/\/www.newslab.sk\/en\/importance-and-diagnostic-of-anti-phospholipid-antibodies-in-women-with-reproductive-disorders\/","title":{"rendered":"Importance and diagnostic of anti-phospholipid antibodies in women with reproductive disorders"},"content":{"rendered":"

*All tables, charts, graphs and pictures that are featured in this article can be found in the .pdf attachment at the end of the paper.<\/strong><\/span><\/p>\n

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\u00davod<\/strong><\/p>\n

Z\u00e1porne nabit\u00e9 fosfolipidy s\u00fa podstatnou zlo\u017ekou v\u0161etk\u00fdch membr\u00e1n, preto s\u00fa vhodn\u00fdm antig\u00e9nom pre antifosfolipidov\u00e9 protil\u00e1tky (APLA)(1). Tieto protil\u00e1tky sa via\u017eu aj na prote\u00edny, ktor\u00e9 vytv\u00e1raj\u00fa komplexy s fosfolipidmi, kam zara\u010fujeme<\/p>\n

napr\u00edklad \u00df-2-glykoprote\u00edn I (\u00df2GPI)(2). APLA s\u00fa heterog\u00e9nna skupina protil\u00e1tok, ktor\u00e1 sa podie\u013ea na tvorbe nez\u00e1palov\u00e9ho autoimunitn\u00e9ho ochorenia s n\u00e1zvom antifosfolipidov\u00fd syndr\u00f3m (APS). Okrem v\u00fdskytu APLA v s\u00e9re alebo plazme je toto ochorenie asociovan\u00e9 najm\u00e4 s\u00a0tromb\u00f3zami a poruchami tehotenstva(3). U \u017eien, u ktor\u00fdch bol diagnostikovan\u00fd APS po\u010das tehotenstva, m\u00f4\u017ee d\u00f4js\u0165 ku komplik\u00e1ci\u00e1m, \u010do m\u00f4\u017ee by\u0165 sp\u00f4soben\u00e9 namieren\u00edm APLA proti placente, ke\u010f doch\u00e1dza k preeklampsii, placent\u00e1rnej isuficiencii alebo p\u00f4sobia negat\u00edvne na rozvoj a funkciu trofoblastu(4). Okrem toho m\u00f4\u017ee d\u00f4js\u0165 aj k prestupu APLA cez placentu, \u010do m\u00f4\u017ee vies\u0165 k mozgov\u00fdm abnormalit\u00e1m a po\u0161kodeniu kognit\u00edvnych funkci\u00ed u naroden\u00fdch det\u00ed(5). Tvorba tromb\u00f3zy, ktor\u00e1 n\u00e1sledne po\u0161kodzuje placentu, m\u00f4\u017ee vznika\u0165 vplyvom APLA na zr\u00fdchlenie koagul\u00e1cie, zn\u00ed\u017eenie fibrinol\u00fdzy(6), aktiv\u00e1ciou endotelov\u00fdch buniek alebo komplementu(7). APS sa v praxi del\u00ed na prim\u00e1rny a sekund\u00e1rny APS, pri\u010dom prim\u00e1rny APS je ozna\u010dovan\u00fd vtedy, ke\u010f vznikol bez nejakej zjavnej pr\u00ed\u010diny, zatia\u013e \u010do sekund\u00e1rny APS vznikol v\u00a0d\u00f4sledku pr\u00edtomnosti nejak\u00e9ho in\u00e9ho ochorenia \u010di infekcie(8). Diagn\u00f3za APS je stanoven\u00e1 na z\u00e1klade sapporsk\u00fdch krit\u00e9ri\u00ed, pod\u013ea ktor\u00fdch je APS diagnostikovan\u00e9 vtedy, ke\u010f je stanoven\u00e9 aspo\u0148 jedno klinick\u00e9 krit\u00e9rium (tehotensk\u00e1 morbidita alebo tromb\u00f3za) a jedno laborat\u00f3rne krit\u00e9rium, ktor\u00fdm je v\u00fdskyt APLA. Medzi hlavn\u00e9 APLA patria protil\u00e1tky proti \u00df2GPI (anti-\u00df2GPI) a antikardiolip\u00ednov\u00e9 protil\u00e1tky (ACLA). Okrem hlavn\u00fdch typov APLA rozozn\u00e1vame protil\u00e1tky v tzv. non-krit\u00e9ri\u00e1ch, to s\u00fa napr\u00edklad protil\u00e1tky proti fosfatidylser\u00ednu, etanolam\u00ednu \u010di protromb\u00ednu. V\u0161etky APLA sa stanovuj\u00fa \u0161tandardizovan\u00fdmi testami ELISA, pri\u010dom sa stanovuj\u00fa bu\u010f IgG, alebo IgM izotypy, alebo sa rob\u00ed celkov\u00fd skr\u00edning protil\u00e1tok(9).<\/p>\n

Vysok\u00e1 heterogenita APLA a ich vplyv na priebeh tehotenstva s\u00fa d\u00f4vodom potratov alebo pred\u010dasn\u00fdch p\u00f4rodov. Mnoho lek\u00e1rov v\u0161ak neberie do \u00favahy patologick\u00fd vplyv imunitn\u00e9ho syst\u00e9mu na reprodukciu. Preto bolo na\u0161\u00edm cie\u013eom pouk\u00e1za\u0165 na d\u00f4le\u017eitos\u0165 APLA, a to hlavne t\u00fdch, ktor\u00e9 s\u00fa zaraden\u00e9 do \u201enon-krit\u00e9ri\u00ed\u201c. V tomto projekte sme sa zamerali hlavne na sledovanie v\u00fdskytu APLA u \u017eien s\u00a0diagnostikovanou neplodnos\u0165ou a lie\u010dbu t\u00fdchto protil\u00e1tok.<\/p>\n

\u00a0<\/strong><\/p>\n

Materi\u00e1l a metodika<\/strong><\/p>\n

S\u00fabor tvorilo 1 246 pacientok (vek: 20 \u2013 50 rokov) s\u00a0diagn\u00f3zou neplodnos\u0165 bez lie\u010dby. S\u00e9rum bolo z\u00edskane z\u00a0krvi odobratej do uzavret\u00e9ho odbern\u00e9ho syst\u00e9mu s g\u00e9lom po\u010das prv\u00e9ho vy\u0161etrenia. V s\u00e9rach pacientok sme sledovali osem typov antifosfolipidov\u00fdch protil\u00e1tok, pri\u010dom sa sledovali anti- \u00df2GPI a ACLA z\u00a0hlavn\u00fdch krit\u00e9ri\u00ed a protil\u00e1tky z \u201enon-krit\u00e9ri\u00ed\u201c: protil\u00e1tky proti fosfatidylser\u00ednu, fosfatidyletanolam\u00ednu, kyseline fosfatidovej, anex\u00ednu V a IgG a IgM protil\u00e1tky proti protromb\u00ednu. Na stanovenie APLA sme pou\u017eili kvantitat\u00edvnu met\u00f3du ELISA, ktor\u00e1 je zalo\u017een\u00e1 na interakcii antig\u00e9n \u2013 protil\u00e1tka (anti- \u00df2GPI \u2013 ORGENTEC, ORG 521S; ACLA \u2013 ORGENTEC, ORG 515S; kyselina antifosfatidov\u00e1 \u2013 Delta Biologicals S.r.l, Subsidiary of ERBA Diagnostics, CA-206; antianex\u00edn V \u2013 IMTEC, ITC59550; antifosfatidylser\u00edn \u2013 IMTEC, ITC59027; antifosfatidyletanolam\u00edn \u2013 IMTEC, ITC59400; antiprotromb\u00edn IgG\/ IgM \u2013 AIDA, REF 10229). S\u00e9ra boli uschov\u00e1van\u00e9 v\u00a0mrazni\u010dke pri teplote ni\u017e\u0161ej ako \u201318 \u00b0C. Antig\u00e9n (napr.: \u00df2GPI) je naviazan\u00fd na pevn\u00fa f\u00e1zu a inkubuje sa so vzorkami, kalibr\u00e1tormi a kontrolami, ktor\u00e9 obsahuj\u00fa prim\u00e1rne protil\u00e1tky interaguj\u00face s antig\u00e9nom na pevnej f\u00e1ze. Na prim\u00e1rne protil\u00e1tky sa n\u00e1sledne<\/p>\n

navia\u017ee sekund\u00e1rna, na ktorej je naviazan\u00fd konjug\u00e1t (chrenov\u00e1 peroxid\u00e1za). V\u00fdsledok sa stanovuje spektrofotometricky( 10).<\/p>\n

Z\u00edskan\u00e9 v\u00fdsledky sme \u0161tatisticky vyhodnotili pomocou \u0161tatistick\u00e9ho programu StatsDirect Statistal Analysis Software. V pr\u00edpade kvalitat\u00edvnych d\u00e1t sme po\u010d\u00edtali len percentily. Pri testoch, kde sa sledovala lie\u010dba, sme najprv zis\u0165ovali normalitu d\u00e1t pomocou StatsDirectu a n\u00e1sledne sme zvolili pri nenorm\u00e1lnom rozdelen\u00ed d\u00e1t \u0161tatistick\u00fd Mannov-Whitneyho test (sledovanie \u00fa\u010dinnosti lie\u010dby v pr\u00edpade protil\u00e1tok proti fosfatidylser\u00ednu, fosfatidyletanolam\u00ednu, anex\u00ednu V a\u00a0protromb\u00ednu IgG). Pri sledovan\u00ed lie\u010dby v pr\u00edpade protil\u00e1tok proti IgM a \u00df2GPI sme zistili norm\u00e1lne rozdelenie d\u00e1t, preto sme vyu\u017eili t-test paired. V\u00fdsledky sme pova\u017eovali za \u0161tatisticky v\u00fdznamn\u00e9, ke\u010f p-hodnota bola men\u0161ia ako 0,05.<\/p>\n

\u00a0<\/strong><\/p>\n

V\u00fdsledky<\/strong><\/p>\n

Z 1 246 pacientok bolo 24 % \u017eien pozit\u00edvnych na niektor\u00fa protil\u00e1tku z APLA (tabu\u013eka 1)<\/em><\/strong>. Z hlavn\u00fdch krit\u00e9ri\u00ed sa naj\u010dastej\u0161ie vyskytovali protil\u00e1tky anti-\u00df2GPI (1,13 %). ACLA sa vyskytovali iba u 0,40 % pacientok, \u010di\u017ee mali najni\u017e\u0161ie zast\u00fapenie zo v\u0161etk\u00fdch APLA, ktor\u00e9 sme sledovali. Z \u201enon-krit\u00e9ri\u00ed\u201c sa naj\u010dastej\u0161ie vyskytovali protil\u00e1tky proti fosfatidylser\u00ednu (12,43 %). Tieto protil\u00e1tky mali najvy\u0161\u0161ie zast\u00fapenie zo v\u0161etk\u00fdch sledovan\u00fdch APLA. IgM protil\u00e1tky proti protromb\u00ednu boli pozit\u00edvne u 8,51 % pacientok a IgG antiprotrob\u00ednov\u00e9 protil\u00e1tky boli pozit\u00edvne u 5,58 % pacientok. Protil\u00e1tky proti placent\u00e1rnemu prote\u00ednu anex\u00ednu V boli pozit\u00edvne u 1,59 % \u017eien, zatia\u013e \u010do fosfatidyletanolam\u00ednov\u00e9 protil\u00e1tky boli pozit\u00edvne u 0,92 % pacientok. Z \u201enon-krit\u00e9ri\u00ed\u201c boli najmenej zast\u00fapen\u00e9 protil\u00e1tky proti kyseline fosfatidovej, ktor\u00e1 bola pozit\u00edvna iba u 0,70 % \u017eien, \u010do je o 0,30 % vy\u0161\u0161\u00ed v\u00fdskyt ako v pr\u00edpade ACLA. Zast\u00fapenie jednotliv\u00fdch protil\u00e1tok mo\u017eno vidie\u0165 v tabu\u013eke 1<\/em><\/strong>.<\/p>\n

ACLA ako najmenej zast\u00fapen\u00e9 protil\u00e1tky mali najvy\u0161\u0161iu kombin\u00e1ciu s in\u00fdm typom APLA (100 %). Najviac sa vyskytovali v kombin\u00e1cii s protil\u00e1tkami proti \u00df2GPI a\u00a0fosfatidylser\u00ednu (pri oboch 80 %). Fosfatidyletanolam\u00ednov\u00e9 protil\u00e1tky boli v kombin\u00e1cii s in\u00fdmi APLA v 81,82 %, pri\u010dom najviac sa vyskytovali s protil\u00e1tkami fosfatidylser\u00ednu (88,89 %). Protil\u00e1tky proti kyseline fosfatidovej boli v kombin\u00e1cii s in\u00fdmi APLA u\u00a02 z 3 pozit\u00edvnych pacientov. A\u017e 100 % kombin\u00e1ciu mali s ACLA, anti-\u00df2GPI a fosfatidylser\u00ednovymi protil\u00e1tkami. Anti-\u00df2GPI protil\u00e1tky boli pozit\u00edvne s viacer\u00fdmi protil\u00e1tkami u 42,86 % pacientok. Naj\u010dastej\u0161iu kombin\u00e1ciu mali s ACLA a\u00a0fosfatidylser\u00ednov\u00fdmi protil\u00e1tkami (pri oboch 66,67 %). Protromb\u00ednov\u00e9 IgG protil\u00e1tky sa vyskytovali v kombin\u00e1cii s in\u00fdmi APLA \u010dastej\u0161ie (32,31 %) ne\u017e IgM protromb\u00ednov\u00e9 protil\u00e1tky (30,30 %). IgG protil\u00e1tky proti protromb\u00ednu boli najviac v\u00a0kombin\u00e1cii s protil\u00e1tkami proti fosfatidylser\u00ednu a IgM protil\u00e1tkami proti protrob\u00ednu (pri oboch 47,62 %). IgM boli naj\u010dastej\u0161ie v\u00a0kombin\u00e1cii s protil\u00e1tkami proti fosfatidylser\u00ednu (43,33 %). Fosfatidylser\u00ednov\u00e9 protil\u00e1tky mali najni\u017e\u0161ie percento v\u00a0kombin\u00e1cii s in\u00fdmi protil\u00e1tkami (28,19 %), pri\u010dom najviac bol pozit\u00edvny s IgM protil\u00e1tkami proti protromb\u00ednu (30,95 %). V\u00fdsledky je mo\u017en\u00e9 vidie\u0165 v tabu\u013eke 2<\/em><\/strong>.<\/p>\n

Okrem v\u00fdskytu jednotliv\u00fdch APLA sme sledovali ich v\u00fdskyt vzh\u013eadom na vek. Pacientky sme rozdelili do 4 vekov\u00fdch skup\u00edn: 20 \u2013 29 rokov, 30 \u2013 35 rokov, 36 \u2013 40 rokov a 41 \u2013 50 rokov. Z\u00e1vislos\u0165 protil\u00e1tok od veku sme zaznamenali iba v pr\u00edpade protil\u00e1tok proti \u00df2GPI a protromb\u00ednu IgG (graf 1)<\/em><\/strong>. Okrem toho protil\u00e1tky proti anex\u00ednu V boli vy\u0161\u0161ie u\u00a0star\u0161\u00edch \u017eien, ale rozdiel nie je \u0161tatisticky v\u00fdznamn\u00fd. V\u00fdskyt ostatn\u00fdch<\/p>\n

protil\u00e1tok nez\u00e1visel od veku. Na z\u00e1klade dostupn\u00fdch inform\u00e1ci\u00ed o pacientkach sme vybrali s\u00fabor pacientok, u ktor\u00fdch bolo mo\u017en\u00e9 sledova\u0165 vplyv lie\u010dby na v\u00fdskyt APLA. T\u00fdmto \u017een\u00e1m bol nasaden\u00fd LMWH (low molecular hepariny), <\/em>aspir\u00edn, vitam\u00edn D a kortikoidy. Sledovali sme obsah protil\u00e1tok pred nasaden\u00edm lie\u010dby a\u00a0obsah protil\u00e1tok po nasaden\u00ed lie\u010dby. Okrem protil\u00e1tok IgG proti protromb\u00ednu do\u0161lo u v\u0161etk\u00fdch pacientok k poklesu APLA po nasaden\u00ed lie\u010dby (tabu\u013eka 3)<\/em><\/strong>. Niektor\u00e9 pacientky boli pozit\u00edvne na viacero APLA naraz, pri\u010dom po nasaden\u00ed lie\u010dby do\u0161lo vo v\u0161etk\u00fdch pr\u00edpadoch k poklesu protil\u00e1tok, ktor\u00e9 boli pred lie\u010dbou zv\u00fd\u0161en\u00e9. Av\u0161ak v niektor\u00fdch pr\u00edpadoch po nasaden\u00ed lie\u010dby do\u0161lo k vzostupu in\u00e9ho typu protil\u00e1tok, ktor\u00e9 pred lie\u010dbou pozit\u00edvne neboli. Naj\u010dastej\u0161ie boli takto zv\u00fd\u0161en\u00e9 protil\u00e1tky proti anex\u00ednu V a oba izotypy protromb\u00ednov\u00fdch protil\u00e1tok. Niektor\u00fdm pacientkam sa podarilo po nasaden\u00ed lie\u010dby otehotnie\u0165, av\u0161ak presn\u00e9 inform\u00e1cie o poklese neplodnosti a \u00faspe\u0161nosti tehotenstva nie s\u00fa k dispoz\u00edcii vzh\u013eadom na ukon\u010denie \u0161t\u00fadie pred z\u00edskan\u00edm t\u00fdchto inform\u00e1ci\u00ed.<\/p>\n

\u00a0<\/strong><\/p>\n

Diskusia<\/strong><\/p>\n

V na\u0161ej \u0161t\u00fadii sme sledovali v\u00fdskyt APLA u \u017eien s\u00a0poruchami reprodukcie. Tieto protil\u00e1tky s\u00fa zodpovedn\u00e9 za spont\u00e1nne potraty, vn\u00fatromaternicov\u00fa smr\u0165 plodu, preeklampsiu \u010di \u017eilov\u00fa tromb\u00f3zu(2). Z 1 246 \u017eien bolo 24 % pozit\u00edvnych na niektor\u00fa<\/p>\n

z APLA. Protil\u00e1tky proti ACLA a anti-\u00df2GPI s\u00fa zaraden\u00e9 medzi hlavn\u00e9 krit\u00e9ri\u00e1 APS, no ich v\u00fdskyt u pacientok s\u00a0poruchami reprodukcie je minoritn\u00fd. N\u00e1zory na vplyv pr\u00edtomnosti ACLA a anti-\u00df2GPI protil\u00e1tok na priebeh tehotenstva s\u00fa kontroverzn\u00e9. Na jednej strane sa uv\u00e1dza, \u017ee ACLA sa podie\u013ea na reproduk\u010dn\u00fdch probl\u00e9moch, zatia\u013e \u010do druh\u00e1 strana tvrd\u00ed, \u017ee ACLA nie s\u00fa spojen\u00e9 s tehotenskou morbiditou(11). V na\u0161om s\u00fabore \u017eien nebola frekvencia v\u00fdskytu ACLA protil\u00e1tok u \u017eien s\u00a0poruchami reprodukcie v\u00fdrazn\u00e1 (len 0,4 %), vyskytovali sa v\u017edy v kombin\u00e1cii s in\u00fdm typom APLA. Protil\u00e1tky anti-\u00df2GPI sa v na\u0161om s\u00fabore vyskytoval len u 1,13 % \u017eien. Anti-\u00df2GPI sa vyskytovali hlavne v kombin\u00e1cii s fosfatidylser\u00ednov\u00fdmi protil\u00e1tkami a s ACLA. Prepojenie medzi ACLA a anti-\u00df2GPI m\u00f4\u017ee by\u0165 sp\u00f4soben\u00e9 t\u00fdm, \u017ee ACLA maj\u00fa epitop na bielkovine \u00df2GPI, preto s\u00fa schopn\u00e9 priamo sa na\u0148 viaza\u0165. V pr\u00edpade v\u00fdskytu dvoch hlavn\u00fdch typov protil\u00e1tok u neplodn\u00fdch \u017eien sa zvy\u0161uje pravdepodobnos\u0165 vzniku APS aj \u0165a\u017e\u0161ie zdravotn\u00e9 probl\u00e9my po\u010das tehotenstva(12).<\/p>\n

V na\u0161om s\u00fabore neplodn\u00fdch \u017eien sa naj\u010dastej\u0161ie vyskytovali protil\u00e1tky proti fosfatidylser\u00ednu (12,43 %). Aj \u0161t\u00fadie Nayfe a kol. (2013) a \u017digona a kol. (2013) uv\u00e1dzaj\u00fa, \u017ee najviac sa na poruch\u00e1ch tehotenstva podie\u013eaj\u00fa fosfatidylser\u00ednov\u00e9 protil\u00e1tky. Zv\u00fd\u0161en\u00e9 boli aj protil\u00e1tky proti protromb\u00ednu. Viac sa vyskytoval izotyp IgM ne\u017e IgG, no vo v\u00e4\u010d\u0161ine \u0161t\u00fadi\u00ed je s\u00a0APS najviac sp\u00e1jan\u00fd IgG izotyp. Predpoklad\u00e1 sa, \u017ee v\u00fdskyt IgM m\u00f4\u017ee by\u0165 spojen\u00fd s prebiehaj\u00facim infek\u010dn\u00fdm stavom(15). IgG<\/p>\n

izotypy s\u00fa sp\u00e1jan\u00e9 hlavne so stratami plodu v skor\u00fdch f\u00e1zach tehotenstva(16). Protil\u00e1tky proti protromb\u00ednu maj\u00fa \u010dast\u00e9 kr\u00ed\u017eov\u00e9 reakcie aj s fosfatidylser\u00ednov\u00fdmi protil\u00e1tkami, a\u00a0tak\u00e1to kombin\u00e1cia sa podie\u013ea na zv\u00fd\u0161en\u00fdch tromb\u00f3zach a\u00a0poruch\u00e1ch tehotenstva(9). V na\u0161om pr\u00edpade bol tak\u00fdto kombinovan\u00fd v\u00fdskyt zisten\u00fd medzi fosfatidylser\u00ednov\u00fdmi protil\u00e1tkami a IgG protromb\u00ednov\u00fdmi protil\u00e1tkami (u 47,62 % \u017een) a\u00a0\u010falej bol zisten\u00fd medzi fosfatidylser\u00ednov\u00fdmi protil\u00e1tkami a\u00a0IgM protromb\u00ednov\u00fdmi protil\u00e1tkami (u 43,33 % \u017eien). Viacer\u00e9 \u0161t\u00fadie uv\u00e1dzaj\u00fa, \u017ee protromb\u00ednov\u00e9 protil\u00e1tky s\u00fa dependentn\u00e9 od fosfatidylser\u00ednu, preto sa odpor\u00fa\u010da vy\u0161etrova\u0165 fosfatidylser\u00ednov\u00e9 aj protromb\u00ednov\u00e9 protil\u00e1tky s\u00fa\u010dasne v jednom behu ELISA. Tak\u00e9to vy\u0161etrenie zlep\u0161\u00ed kvalitu diagnostick\u00e9ho testu zachyten\u00edm v\u00e4\u010d\u0161ieho mno\u017estva protil\u00e1tok, preto k nemu<\/p>\n

chceme prist\u00fapi\u0165 aj my. \u010eal\u0161\u00edmi v\u00fdznamn\u00fdmi APLA s\u00fa protil\u00e1tky proti fosfatidyletanolam\u00ednu, ktor\u00e9 sme detegovali u 0,92 % pacientok. Sugi a kol. (2004) vo svojej \u0161t\u00fadii uv\u00e1dzaj\u00fa vy\u0161\u0161\u00ed v\u00fdskyt t\u00fdchto protil\u00e1tok u \u017eien s poruchami tehotenstva v skor\u0161ej aj v\u00a0neskor\u0161ej f\u00e1ze gravidity. Protil\u00e1tky proti anex\u00ednu V boli detegovan\u00e9 u 1,59 % \u017eien. Anex\u00edn V je bielkovina produkovan\u00e1 placentou, ktor\u00e1 m\u00e1 ve\u013emi dobr\u00fa afinitu k fosfolipidom a\u00a0via\u017ee sa aj na povrch trombocytov. V\u010faka tejto afinite k\u00a0fosfolipidom vytv\u00e1ra mrie\u017eku okolo membr\u00e1ny, \u010d\u00edm zabra\u0148uje aktivite koagula\u010dnej kask\u00e1dy. V d\u00f4sledku zv\u00fd\u0161enej produkcie protil\u00e1tok proti anex\u00ednu V doch\u00e1dza k vy\u0161tiepovaniu tejto bielkoviny z povrchu a sp\u00fa\u0161\u0165a sa koagul\u00e1cia. V\u00fdsledkom je zv\u00fd\u0161en\u00e9 riziko straty plodu(18). Ve\u013emi \u010dast\u00fdm javom je s\u00fa\u010dasn\u00fd v\u00fdskyt protil\u00e1tok proti r\u00f4znym antig\u00e9nom, napr. kombin\u00e1cia protil\u00e1tok proti anex\u00ednu V s protil\u00e1tkami proti fosfatidylser\u00ednu sa vyskytla u 63,64 % \u017eien. Plodnos\u0165 \u017eeny z\u00e1vis\u00ed od jej veku. Zauj\u00edmalo n\u00e1s, \u010di s\u00fa APLA z\u00e1visle od veku u \u017eien s diagnostikovanou neplodnos\u0165ou, preto\u017ee publik\u00e1ci\u00ed o vplyve veku na APLA je m\u00e1lo. Nezaznamenali sme z\u00e1vislos\u0165 v\u00fdskytu protil\u00e1tok proti fosfolipidom (kardiolip\u00edn, fosfatidylser\u00edn, fosfatidyletanolam\u00edn a\u00a0kyselina fosfatidov\u00e1) od veku. Naopak, zistili sme, \u017ee s rast\u00facim vekom st\u00fapa v\u00fdskyt anti-\u00df2GPI. Mehdi a kol. zistili, \u017ee frekvencia v\u00fdskytu \u00df2GPI u \u017eien st\u00fapa s vekom(19), preto je mo\u017en\u00e9, \u017ee aj protil\u00e1tky proti nemu m\u00f4\u017eu by\u0165 \u010dastej\u0161ie. Podobn\u00fd trend sme zachytili taktie\u017e pri IgG protil\u00e1tkach proti protromb\u00ednu, ale u\u017e nie pri IgM protil\u00e1tkach proti protromb\u00ednu.<\/p>\n

Na\u0161e pacientky s pozit\u00edvnymi APLA boli lie\u010den\u00e9 aspir\u00ednom, LMWH, vitam\u00ednom D a kortikoidmi. Viacer\u00e9 \u0161t\u00fadie pouk\u00e1zali na to, \u017ee lie\u010dba aspir\u00ednom s hepar\u00ednom alebo kortikoidmi je \u00fa\u010dinnej\u0161ia ako lie\u010dba samotn\u00fdm aspir\u00ednom(20,21). Po nasaden\u00ed<\/p>\n

lie\u010dby do\u0161lo poklesu protil\u00e1tok proti fosfatidylser\u00ednu, etanolam\u00ednu a anex\u00ednu V. Protil\u00e1tky proti \u00df2GPI a protromb\u00ednu IgM tie\u017e poklesli, av\u0161ak tento pokles nebol \u0161tatisticky v\u00fdznamn\u00fd. V pr\u00edpade anti-\u00df2GPI to mohlo by\u0165 sp\u00f4soben\u00e9 nedostato\u010dn\u00fdm mno\u017estvom pacientov pozit\u00edvnych na t\u00fato protil\u00e1tku. Protil\u00e1tky proti protromb\u00ednu IgG st\u00fapli v porovnan\u00ed s\u00a0hladinou pred lie\u010dbou. Tento rozdiel v\u0161ak nie je signifikantn\u00fd.<\/p>\n

\u00a0<\/strong><\/p>\n

Z\u00e1ver<\/strong><\/p>\n

Antifosfolipidov\u00e9 protil\u00e1tky sa podie\u013eaj\u00fa na poruch\u00e1ch reprodukcie u takmer \u0161tvrtiny \u017eien s poruchami reprodukcie. V na\u0161ej \u0161t\u00fadii sme uk\u00e1zali \u010dast\u00fd v\u00fdskyt protil\u00e1tok proti fosfatidylser\u00ednu (12,43 %) a protromb\u00ednu (8,51 % \u2013 IgM, 5,58 % \u2013 IgG) u \u017eien s poruchami reprodukcie. Naopak, v\u00fdskyt klasick\u00fdch protil\u00e1tok proti ACLA a anti-\u00df2GPI bol ve\u013emi n\u00edzky (0,40 %, resp. 1,13 %). Po nasaden\u00ed lie\u010dby pacientkam so zv\u00fd\u0161en\u00fdmi APLA (aspir\u00edn, vitam\u00edn D, LMWH a kortikoidy) doch\u00e1dzalo k zn\u00ed\u017eeniu APLA protil\u00e1tok. Lie\u010dbu treba udr\u017eiava\u0165 aj po\u010das gravidity, aby sa predch\u00e1dzalo potratom.<\/p>\n

\u00a0<\/strong><\/p>\n

Literat\u00fara<\/strong><\/p>\n

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  1. Laz\u00far J. Antifosfolipidov\u00fd syndr\u00f3m. Inertn\u00e1 med 2008; 8: 527-531.<\/li>\n
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    Rheumatology 2013; 52: 1358-1367.<\/p>\n

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    1. \u017digon P, \u010cu\u010dnik S, Ambro\u017ei\u010d A, et al. Detection of Antiphosphatidylserine\/ Prothrombin Antibodies and Their Potential Diagnostic Value, Clin. Dev. Immunol 2013; 2013: 1-8.<\/li>\n
    2. Gr\u00f6nwall C, Vas J, Silverman GJ. Protective Roles of Natural IgM Antibodies. Front Immunol 2012; 3: 1-10.<\/li>\n
    3. von Landenberg P, Matthias T, Zaech J, et al. Antiprothrombin antibodies are associated with pregnancy loss in patients with the antiphospholipid syndrome. AJRI 2003; 49: 51-56.<\/li>\n
    4. Sugi T, Matsubayashi H, Inomo A, et al. Antiphosphatidylethanolamine antibodies in recurrent early pregnancy loss and mid-to-late pregnancy loss. J Obstet Gynaecol Res 2004; 30: 326-332.<\/li>\n
    5. Rand JH.Molecular Pathogenesis of the Antiphospholipid Syndrome. Circ Res 2002; 90: 29-37.<\/li>\n
    6. Mehdi H, Aston CE, Sanghera DK, et al. Genetic variation in the apolipoprotein H (beta2-glycoprotein I) gene affects plasma apolipoprotein H concentrations. Hum Genet 1999; 105: 63-71.<\/li>\n
    7. Rai R, Cohen H, Dave M, et al. Randomised controlled trial of aspirin and aspirin plus heparin in pregnant women with recurrent miscarriage associated with phospholipid antibodies (or antiphospholipid antibodies) BMJ 1997; 314: 253-257.<\/li>\n
    8. Silver RK, MacGregor SN, Sholl JS, et al. Comparative trial of prednisone plus aspirin versus aspirin alone in the treatment of anticardiolipin antibody-positive obstetric patients. Am J Obstet Gynecol 1993; 169: 1411-1417.<\/li>\n<\/ol>\n","protected":false},"excerpt":{"rendered":"

      *All tables, charts, graphs and pictures that are featured in this article can be found in the .pdf attachment at the end of the paper.     \u00davod Z\u00e1porne nabit\u00e9 fosfolipidy s\u00fa podstatnou zlo\u017ekou v\u0161etk\u00fdch membr\u00e1n, preto s\u00fa vhodn\u00fdm antig\u00e9nom pre antifosfolipidov\u00e9 protil\u00e1tky (APLA)(1). Tieto protil\u00e1tky sa via\u017eu aj na prote\u00edny, ktor\u00e9 vytv\u00e1raj\u00fa komplexy s<\/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":[291],"tags":[1221,1222,482,1224,681,1223],"class_list":["post-1756","post","type-post","status-publish","format-standard","hentry","category-imunology","tag-antifosfolipidove-protilatky-en","tag-antifosfolipidovy-syndrom-en","tag-antiphospholipid-antibodies","tag-antiphospholipid-syndrome","tag-infertility","tag-neplodnost-en","typ_clanku-original-work"],"acf":{"abstrakt":"

      Antiphospholipid antibodies bind to the phospholipids or complex protein-phospholipid. The occurrence of those antibodies can lead to the creation of thrombosis or pregnancy disorders that are symptoms of non-inflammatory autoimmune disease – antiphospholipid syndrome. Main criteria of antiphospholipid syndrome are cardiolipin antibodies and antibodies against \u00df-2-glycoprotein 1. Other types of antibodies detected in sera of patients are antibodies against phosphatidylserine, phosphatidylethanolamine, prothrombin or annexin V. Origin and development of those antibodies are not known, and there is ongoing discussion which antibodies are the most present in patients with antiphospholipid syndrome and which ones should be part of main criteria. Therefore, our aim was to observe the occurrence and effect of antiphospholipid antibodies in women with reproductive disorders and their treatment.<\/p>\n

      Keywords: antiphospholipid antibodies, antiphospholipid syndrome, infertility<\/p>\n","casopis":[{"ID":1633,"post_author":"7","post_date":"2019-05-09 08:56:48","post_date_gmt":"2019-05-09 06:56:48","post_content":"

        \r\n \t
      • Primary pancreatic liposarcoma \u2013 the case report and iterature review<\/li>\r\n \t
      • DNA sequencing in laboratory diagnostics of bacterial pathogens<\/li>\r\n \t
      • Importance and diagnostic of anti-phospholipid antibodies in women with reproductive disorders<\/li>\r\n \t
      • Development of complex chromosome rearrangements in a patient with ALL<\/li>\r\n \t
      • HCV infection \u2013 more than 20 years of drug development<\/li>\r\n<\/ul>","post_title":"newsLab","post_excerpt":"","post_status":"publish","comment_status":"closed","ping_status":"closed","post_password":"","post_name":"newslab-3","to_ping":"","pinged":"","post_modified":"2019-05-09 08:56:48","post_modified_gmt":"2019-05-09 06:56:48","post_content_filtered":"","post_parent":0,"guid":"http:\/\/www.newslab.sk\/?post_type=casopis&p=1633","menu_order":0,"post_type":"casopis","post_mime_type":"","comment_count":"0","filter":"raw"}],"strana":"5-8","upload_clanok":{"ID":1754,"id":1754,"title":"V\u00fdznam a diagnostika antifosfolipidov\u00fdch protil\u00e1tok u \u017eien s poruchami","filename":"V\u00fdznam-a-diagnostika-antifosfolipidov\u00fdch-protil\u00e1tok-u-\u017eien-s-poruchami.pdf","filesize":293514,"url":"https:\/\/www.newslab.sk\/wp-content\/uploads\/2019\/05\/V\u00fdznam-a-diagnostika-antifosfolipidov\u00fdch-protil\u00e1tok-u-\u017eien-s-poruchami.pdf","link":"https:\/\/www.newslab.sk\/en\/importance-and-diagnostic-of-anti-phospholipid-antibodies-in-women-with-reproductive-disorders\/vyznam-a-diagnostika-antifosfolipidovych-protilatok-u-zien-s-poruchami-2\/","alt":"","author":"7","description":"","caption":"","name":"vyznam-a-diagnostika-antifosfolipidovych-protilatok-u-zien-s-poruchami-2","status":"inherit","uploaded_to":1756,"date":"2019-05-09 11:51:09","modified":"2019-05-09 11:51:09","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\/1756","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=1756"}],"version-history":[{"count":0,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/posts\/1756\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/media?parent=1756"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/categories?post=1756"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/tags?post=1756"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}