{"id":1242,"date":"2017-09-27T10:11:33","date_gmt":"2017-09-27T08:11:33","guid":{"rendered":"http:\/\/www.newslab.sk\/2017\/09\/27\/prve-skusenosti-so-stanovenim-degalaktozylovaneho-iga1-v-diagnostike-a-monitorovani-pacientov-s-iga-nefropatiou\/"},"modified":"2017-09-27T10:40:10","modified_gmt":"2017-09-27T08:40:10","slug":"the-first-results-of-galactose-deficient-iga1-measurement-in-diagnosis-and-monitoring-of-patients-with-iga-ne-phropathy","status":"publish","type":"post","link":"https:\/\/www.newslab.sk\/en\/the-first-results-of-galactose-deficient-iga1-measurement-in-diagnosis-and-monitoring-of-patients-with-iga-ne-phropathy\/","title":{"rendered":"The first results of galactose-deficient IgA1 measurement in diagnosis and monitoring of patients with IgA ne- phropathy"},"content":{"rendered":"
*All tables, charts, graphs and pictures that are featured in this article can be found in the .pdf <\/span>\r\nattachment at the end of the paper.<\/span> <\/strong><\/pre>\n
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\u00dav<\/strong>od<\/strong><\/p>\n
IgA nefropatia (IgAN) je naj\u010dastej\u0161ou prim\u00e1rnou glomerulonefrit\u00eddou u adolescentov a dospel\u00fdch. Od n\u00e1stupu klinick\u00fdch pr\u00edznakov progreduje do koncov\u00e9ho \u0161t\u00e1dia obli\u010dkov\u00e9ho ochorenia 1,5 % pacientov ro\u010dne \u00a0a pribli\u017ene 25 \u2013 30 % pacientov vy\u017eaduje \u00a0dial\u00fdzu alebo \u00a0transplant\u00e1ciu obli\u010dky do 20 \u2013 25 rokov trvania \u00a0ochorenia. Japonsk\u00ed autori \u00a0uv\u00e1dzaj\u00fa aj pomerne vysok\u00fd v\u00fdskyt subklinickej \u00a0formy IgAN (\u201elanthanic IgAN\u201c), ktor\u00fa histologicky potvrdili u 16 % potenci\u00e1lnych \u017eij\u00facich darcov obli\u010dky bez ak\u00fdchko\u013evek klinick\u00fdch prejavov choroby(1). Typick\u00fdmi klinick\u00fdmi pr\u00edznakmi v \u010dase stanovenia diagn\u00f3zy s\u00fa hemat\u00faria alebo \u00a0kombin\u00e1cia hemat\u00farie s mierne \u00a0a\u017e \u00a0stredne z\u00e1va\u017enou protein\u00fariou (< 2\u2008g\/24 h), pri\u010dom hemat\u00faria je \u010dasto asociovan\u00e1 s infekciou horn\u00fdch \u00a0d\u00fdchac\u00edch ciest. Niektor\u00ed pacienti maj\u00fa u\u017e v \u010dase stanovenia diagn\u00f3zy pr\u00edznaky \u00a0zlyh\u00e1vania obli\u010diek a hypertenziu(2). Pre IgAN je charakteristick\u00e1 mu\u017esk\u00e1 predispoz\u00edcia, n\u00e1stup ochorenia v druhej \u00a0a\u017e tretej \u00a0dek\u00e1de \u017eivota, \u0161irok\u00e9 \u00a0spektrum klinick\u00fdch pr\u00edznakov \u00a0a variabiln\u00e1 \u00a0r\u00fdchlos\u0165 \u00a0progresie ochorenia po stanoven\u00ed diagn\u00f3zy(1).<\/p>\n
Potvrdenie diagn\u00f3zy IgAN na\u010falej \u00a0vy\u017eaduje \u00a0biopsiu obli\u010dky(2). Charakteristick\u00fdm histopatologick\u00fdm znakom s\u00fa ren\u00e1lne \u00a0depozity cirkuluj\u00facich imunokomplexov s d\u00f4kazom imunoglobul\u00ednu A (IgA) v mezangiu glomerulov \u010dasto sprev\u00e1dzan\u00e9ho imunoglobul\u00ednom G (IgG) a C3 zlo\u017ekou \u00a0komplementu(3). Pribli\u017ene 50 % pacientov s IgAN m\u00e1 zv\u00fd\u0161en\u00e9 hodnoty IgA a IgA obsahuj\u00facich imunokomplexy v s\u00e9re(4).<\/p>\n
IgAN je definovan\u00e1 ako \u00a0autoimunitn\u00e9 ochorenie s typickou patogen\u00e9zou viacer\u00fdch \u00faderov (multi-hit), ktor\u00e1 je modulovan\u00e1 \u00a0r\u00f4znymi genetick\u00fdmi aj vonkaj\u0161\u00edmi \u00a0faktormi. K\u013e\u00fa\u010dov\u00fa \u00falohu \u00a0v patogen\u00e9ze IgAN m\u00e1 \u00a0degalaktozylovan\u00e1 forma \u00a0IgA1 (Gd-IgA1)(2). P\u00f4vod \u00a0buniek secernuj\u00facich Gd-IgA1 nie je presne zn\u00e1my. Cirkuluj\u00faci IgA1 je produkovan\u00fd hlavne v kostnej dreni, k\u00fdm Gd-IgA1 m\u00f4\u017ee \u00a0by\u0165 syntetizovan\u00fd ako \u00a0odpove\u010f na\u00a0 slizni\u010dn\u00fa \u00a0infekciu. \u00a0Predpoklad\u00e1 sa, \u00a0\u017ee abnormality \u00a0v slizni\u010dnej \u00a0odpovedi na be\u017en\u00fd \u00a0mikrobi\u00e1lny \u00a0alebo potravinov\u00fd \u00a0antig\u00e9n m\u00f4\u017eu \u00a0preto \u00a0vies\u0165 k produkcii Gd-IgA1(5).<\/p>\n
Podtriedy IgA1 a IgA2 sa l\u00ed\u0161ia hlavne pr\u00edtomnos\u0165ou unik\u00e1tnej dlhej z\u00e1vesnej oblasti tzv. \u201ehinge\u201c regi\u00f3nu u IgA1. T\u00e1to z\u00e1vesn\u00e1 oblas\u0165 je tvoren\u00e1 re\u0165azcom 18 aminokysel\u00edn, na ktor\u00e9 sa m\u00f4\u017ee \u00a0viaza\u0165 a\u017e \u0161es\u0165 \u00a0sacharidov\u00fdch zvy\u0161kov O-glykozylovou v\u00e4zbou(6). (obr\u00e1zok <\/em><\/strong>1)<\/em><\/strong><\/p>\n
U zdrav\u00fdch \u00a0jedincov je v\u00e4\u010d\u0161ina O-re\u0165azcov kompletne glykozylovan\u00e1 s Gal (najmenej \u0161tyri a\u017e \u00a0\u0161es\u0165 re\u0165azcov \u00a0je kompletn\u00fdch), \u00a0k\u00fdm v\u00e4\u010d\u0161ina re\u0165azcov \u00a0u pacientov s IgAN je nekompletne galakozylovan\u00fdch alebo \u00a0skr\u00e1ten\u00fdch (najviac \u00a0dva re\u0165azce zo \u0161iestich s\u00fa kompletn\u00e9)(6). Gd-IgA1 sa uplat\u0148uje ako autoantig\u00e9n, ktor\u00fd je rozli\u0161ovan\u00fd \u0161pecifick\u00fdmi autoprotil\u00e1tkami s n\u00e1slednou tvorbou \u00a0cirkuluj\u00facich imunokomplexov(3).<\/p>\n
Vysok\u00e9 \u00a0koncentr\u00e1cie Gd-IgA1 sami \u00a0o sebe neved\u00fa \u00a0k po\u0161kodeniu obli\u010diek. \u00a0V patogen\u00e9ze ochorenia vy\u00fas\u0165uj\u00facej \u00a0do ren\u00e1lneho po\u0161kodenia sa uplat\u0148uj\u00fa \u0161tyri procesy \u2013 aberantn\u00e1\u00a0 glykozyl\u00e1cia IgA1, synt\u00e9za protil\u00e1tok proti \u00a0Gd-IgA1, form\u00e1cia imunokomplexov a ukladanie imunokomplexov v mezangiu obli\u010diek(5).<\/p>\n
Tieto komplexy nie s\u00fa efekt\u00edvne\u00a0 metabolizovan\u00e9 pe\u010de\u0148ou, \u010do vedie k tvorbe \u00a0glomerulov\u00fdch depozitov, aktiv\u00e1cii a prolifer\u00e1cii mezangi\u00e1lnych buniek, lok\u00e1lnej aktiv\u00e1cii komplementu, produkcii \u00a0extracelul\u00e1rnej matrix \u00a0a cytok\u00ednov, ktor\u00e9 \u00a0m\u00f4\u017eu ovplyvni\u0165 expresiu g\u00e9nov \u00a0podocytmi a glomerul\u00e1rnu permeabilitu. Postihnutie mezangia a podocytov vedie k protein\u00farii a tubulointerstici\u00e1lnym zmen\u00e1m(2).<\/p>\n
IgAN predstavuje syst\u00e9mov\u00e9 ochorenie, \u010do potvrdzuje aj fakt, \u017ee pri transplant\u00e1cii obli\u010dky darcu \u00a0so subklinickou IgAN pr\u00edjemcovi \u00a0s non-IgAN obli\u010dkovou chorobou do\u0161lo \u00a0kr\u00e1tko po transplant\u00e1cii obli\u010dky k vymiznutiu depozitov IgA(5).<\/p>\n
Prv\u00e9 testy na detekciu Gd-IgA1 boli zalo\u017een\u00e9 na v\u00e4zbovej aktivite vo\u010di \u0161pecifick\u00fdm lekt\u00ednom \u2013 helix aspersa (HAA), helix promatia (HPA) alebo \u00a0vicia villosa (VV) \u2013 pr\u00edrodne \u00a0sa vyskytuj\u00face molekuly \u00a0s vysokou \u00a0v\u00e4zbovou kapacitou vo\u010di sacharidov\u00fdm zvy\u0161kom so \u0161pecifickos\u0165ou ku GalNAc zvy\u0161kom. Yasutake a kol. vyvinuli ELISA test pou\u017eit\u00edm novej Gd-IgA1 \u0161pecifickej monoklonovej protil\u00e1tky KM55(7). V s\u00fa\u010dasnosti s\u00fa pre klinick\u00fa prax dostupn\u00e9 aj \u010fal\u0161ie \u00a0testy, \u00a0ktor\u00fdmi mo\u017eno stanovi\u0165 \u00a0koncentr\u00e1cie Gd-IgA1. V na\u0161ej pr\u00e1ci \u00a0sme pou\u017eili syst\u00e9m Human \u00a0Galactose-Deficient IgA1<\/p>\n
ELISA Kit firmy \u00a0Abbexa. \u00a0Princ\u00edpom vy\u0161etrenia \u00a0je \u00a0zmena sfarbenia produktu po naviazan\u00ed protil\u00e1tky (chicken anti-Galactose-Deficient IgA1) na cie\u013eov\u00fd antig\u00e9n (Protein A). Intenzita novovzniknut\u00e9ho \u017elt\u00e9ho \u00a0sfarbenia je proporcion\u00e1lna ku koncentr\u00e1cii GdIgA1. O.D. absorbancia je meran\u00e1 spektrofotometricky pri 450\u2008nm.<\/p>\n
Cie\u013eom na\u0161ej pr\u00e1ce bolo \u00a0overenie klinickej vyu\u017eite\u013enosti komer\u010dne dostupn\u00e9ho setu na stanovenie Gd-IgA1 pri diagnostike a sledovan\u00ed aktivity IgA nefropatie.<\/p>\n
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Materi\u00e1l a metodika<\/strong><\/p>\n
Do \u00a0nami\u00a0 \u00a0vy\u0161etrovan\u00e9ho s\u00faboru sme \u00a0zaradili\u00a0 \u00a087 \u00a0vzoriek \u00a0pacientov a \u00a0zdrav\u00fdch kontrol \u00a0zozbieran\u00fdch v obdob\u00ed\u00a012. 2016 \u2013 30. 04. 2017. Cel\u00fd s\u00fabor sme rozdelili na \u0161ty<\/span>ri skupiny:<\/p>\n
\u2013 skupina 1: \u00a0pacienti \u00a0so z\u00e1kladnou diagn\u00f3zou IgAN po transplant\u00e1cii obli\u010dky (n = 14),<\/p>\n
\u2013 \u00a0skupina 2: pacienti po transplant\u00e1cii obli\u010dky, ktor\u00ed nemaj\u00fa IgAN ako z\u00e1kladn\u00fa diagn\u00f3zu a ani glomerulov\u00e9 zmeny v protokol\u00e1rnej biopsii transplantovanej obli\u010dky (n = 25),<\/p>\n
\u2013 \u00a0skupina 3: pacienti s biopticky \u00a0dok\u00e1zanou IgAN (n = 4) a suspektnou IgAN na z\u00e1klade klinick\u00fdch a laborat\u00f3rnych n\u00e1lezov (n = 23),<\/p>\n
\u2013 \u00a0skupina 4: zdrav\u00e9 \u00a0kontroly (n = 21).<\/p>\n
Detailnej\u0161ie \u00fadaje \u00a0o podskupin\u00e1ch vy\u0161etrovan\u00e9ho s\u00faboru s\u00fa v tabu\u013eke 1<\/em><\/strong>.<\/p>\n
Pacienti s IgAN v skupine 1 boli 9 \u2013 83 mesiacov po transplant\u00e1cii obli\u010dky, naj\u010dastej\u0161\u00edm typom \u00a0lie\u010dby bola \u00a0trojkombin\u00e1cia \u00a0imunosupres\u00edv \u2013 kortikoidy, mykofenol\u00e1t sodn\u00fd \u00a0a takrolimus \u00a0(78,5 \u00a0% pacientov). 12 \u00a0pacientov malo \u00a0funk\u010dn\u00fa transplantovan\u00fa obli\u010dku, 1 pacientka mala \u00a0zlyh\u00e1vaj\u00faci \u00a0\u0161tep a 1 pacient bol po zlyhan\u00ed \u0161tepu v d\u00f4sledku rekurencie IgAN znovuzaraden\u00fd do \u00a0hemodialyza\u010dn\u00e9ho programu. V skupine 2 mali v\u0161etci \u00a0pacienti stabiln\u00fa funkciu transplantovanej obli\u010dky, 88 % z nich malo \u0161tandardn\u00fa imunosupres\u00edvnu lie\u010dbu (kortikoidy, mykofenol\u00e1t sodn\u00fd \u00a0a takrolimus) a doba \u00a0od transplant\u00e1cie bola 1 \u2013 83 mesiacov. Na \u0161tatistick\u00e9 spracovanie sme pou\u017eili Kruskal-Wallisov test, \u00fadaje \u00a0sme spracovali programom SPSS1.<\/p>\n
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V<\/strong>\u00fdsledky<\/strong><\/p>\n
Priemern\u00e9 s\u00e9rov\u00e9 koncentr\u00e1cie Gd-IgA1 v skupin\u00e1ch 1, 2, 3 a 4 boli: 58,05\u2008\u03bcg\/l, 10,53\u2008\u03bcg\/l, 165,2\u2008\u03bcg\/l a 6,4\u2008\u03bcg\/l \u00a0\u2013 graf 1<\/em><\/strong>. \u0160tatisticky v\u00fdznamn\u00e9 rozdiely medzi \u00a0vy\u0161etrovan\u00fdmi skupinami a kontrolami a ani medzi \u00a0jednotliv\u00fdmi skupinami pacientov sme nezistili.<\/p>\n
Zv\u00fd\u0161en\u00e9 \u00a0hodnoty Gd-IgA1 malo \u00a06 pacientov (7 %) z cel\u00e9ho s\u00faboru \u2013 jedna \u00a0pacientka v skupine 1 a piati pacienti zo skupiny 3. Koncentr\u00e1cie Gd-IgA1 u t\u00fdchto \u00a0pacientov dosahovali 43 \u2013 152-n\u00e1sobok priemernej koncentr\u00e1cie Gd-IgA1 u zdrav\u00fdch \u00a0kontrol. \u00a0V tabu\u013eke 2 <\/em><\/strong>uv\u00e1dzame vybran\u00e9 \u00a0klinick\u00e9 a laborat\u00f3rne charakteristiky pacientov so \u00a0zv\u00fd\u0161en\u00fdmi s\u00e9rov\u00fdmi koncentr\u00e1ciami Gd-IgA1. U pacientky po transplant\u00e1cii obli\u010dky bola koncentr\u00e1cia Gd-IgA1 stanoven\u00e1 v \u010dase ak\u00fatneho zhor\u0161enia funkcie \u00a0\u0161tepu. V histologickom vy\u0161etren\u00ed neboli op\u00edsan\u00e9 patologick\u00e9 morfologick\u00e9 zmeny \u00a0glomerulov, ale ch\u00fdba n\u00e1m \u00a0imunofluorescen\u010dn\u00e9 vy\u0161etrenie. U pacientky 2\u2008s \u00a0histologicky potvrdenou IgAN bol po redukcii \u00a0imunosupresie pri stabilnom funk\u010dnom ren\u00e1lnom n\u00e1leze zaznamenan\u00fd vzostup s\u00e9rov\u00e9ho kreatin\u00ednu a protein\u00farie. Pacienti 3 a 4 nemaj\u00fa realizovan\u00fa ren\u00e1lnu \u00a0biopsiu. \u00a0U t\u00fdchto \u00a0pacientov m\u00f4\u017eu zv\u00fd\u0161en\u00e9 hodnoty Gd-IgA1 podporova\u0165 diagn\u00f3zu IgAN. Prekvapiv\u00e9 s\u00fa n\u00e1lezy u pacientov 5 a 6, ktor\u00ed maj\u00fa biopticky potvrden\u00fa \u00a0FSGS a mal\u00e9 \u00a0abnormality glomerulov s negat\u00edvnou expresiou IgA pri imunofluorescen\u010dnom vy\u0161etren\u00ed. V prvej skupine boli dvaja pacienti so v\u010dasn\u00fdm zlyhan\u00edm transplantovanej obli\u010dky v d\u00f4sledku rekurencie IgAN, u ktor\u00fdch sa zv\u00fd\u0161en\u00e9 hodnoty Gd-IgA1 nepotvrdili.<\/p>\n
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Diskusia<\/strong><\/p>\n
Neinvaz\u00edvne biomarkery IgAN by mohli potenci\u00e1lne \u00a0vies\u0165 ku skor\u0161ej diagnostike ochorenia, k detailnej\u0161iemu monitorovaniu klinick\u00e9ho \u00a0priebehu ako aj odpovede na lie\u010dbu. Hlavn\u00fdm \u00a0kandid\u00e1tom spomedzi t\u00fdchto \u00a0biomarkerov je Gd-IgA1(8). Moldoveanu a kol. vy\u0161etrili Gd-IgA1 ako diagnostick\u00fd marker \u00a0u pacientov s IgAN. Anal\u00fdza ROCC (Receiver \u00a0Operating Characteristic Curve) potvrdila \u00a0senzitivitu 0,77 a \u0161pecifickos\u0165 0,90 pri rozl\u00ed\u0161en\u00ed \u00a0pacientov s IgAN od zdrav\u00fdch \u00a0kontrol(5). Viacer\u00e9 \u00a0\u0161t\u00fadie potvrdili zv\u00fd\u0161enie Gd-IgA1 u pacientov s IgAN v porovnan\u00ed so zdrav\u00fdmi kontrolami(9). V na\u0161om s\u00fabore pacientov sme toto pozorovanie nepotvrdili, \u010do vysvet\u013eujeme mal\u00fdm po\u010dtom pacientov s histologicky potvrdenou IgAN a mo\u017en\u00fdm vplyvom imunosupres\u00edvnej lie\u010dby u \u010dasti pacientov. Zv\u00fd\u0161en\u00e9 \u00a0hodnoty Gd-IgA1 boli op\u00edsan\u00e9 u pacientov kaukazsk\u00e9ho, \u00e1zijsk\u00e9ho aj africk\u00e9ho p\u00f4vodu s vari\u00e1ciou u jednotliv\u00fdch pohlav\u00ed a etnick\u00fdch skup\u00edn. \u00a0Zv\u00fd\u0161en\u00e9 \u00a0hodnoty Gd-IgA1 boli pozorovan\u00e9 aj u 5 % zdrav\u00fdch \u00a0jedincov(8). 40 \u2013 50 % prvostup\u0148ov\u00fdch pr\u00edbuzn\u00fdch chor\u00fdch m\u00e1 \u00a0zv\u00fd\u0161en\u00e9 hodnoty Gd-IgA1 porovnate\u013en\u00e9 s hodnotami pacientov, z \u010doho \u00a0vypl\u00fdva vysok\u00fd podiel dedi\u010dnosti na tomto ochoren\u00ed\u00a0 a taktie\u017e fakt, \u017ee aberantn\u00e1 glykozyl\u00e1cia IgA1 predch\u00e1dza klinicky zjavn\u00fa \u00a0chorobu a predstavuje dedi\u010dn\u00fd \u00a0rizikov\u00fd faktor IgAN. Tento \u00a0dedi\u010dn\u00fd \u00a0defekt v\u0161ak \u00a0neposta\u010duje na vyvolanie IgAN, o \u010dom \u00a0sved\u010d\u00ed \u00a0aj to, \u017ee nie v\u0161etky \u00a0osoby \u00a0so \u00a0zv\u00fd\u0161enou hodnotou Gd-IgA1 maj\u00fa klinick\u00fa symptomatol\u00f3giu ren\u00e1lneho postihnutia a \u017ee pri po\u0161koden\u00ed obli\u010diek sa uplat\u0148uj\u00fa aj \u010fal\u0161ie patofyziologick\u00e9 mechanizmy(5). V na\u0161om s\u00fabore m\u00e1me zaraden\u00fd \u00a0pr\u00edbuzensk\u00fd p\u00e1r rodi\u010d \u2013 die\u0165a, v ktorom \u00a0pr\u00edjemca obli\u010dky m\u00e1 IgAN. Ani jeden z vy\u0161etrovan\u00fdch nem\u00e1 v s\u00fa\u010dasnosti zv\u00fd\u0161en\u00e9 hodnoty Gd-IgA1, av\u0161ak je potrebn\u00e9 sledovanie dynamiky koncentr\u00e1ci\u00ed Gd-IgA1, pr\u00edpadne aj in\u00fdch neinvaz\u00edv- nych markerov IgAN, ktor\u00e9 uv\u00e1dzame v tabu\u013eke 3<\/em><\/strong>. Pre skupinu pacientov s kontraindik\u00e1ciou ren\u00e1lnej \u00a0biopsie, \u00a0ako s\u00fa pacienti so solit\u00e1rnou obli\u010dkou vr\u00e1tane \u017eij\u00facich darcov \u00a0obli\u010dky, je dostupnos\u0165 uveden\u00fdch vy\u0161etren\u00ed ve\u013emi v\u00fdznamn\u00e1.<\/p>\n
V s\u00favislosti so \u00a0zisten\u00edm zv\u00fd\u0161enej hodnoty Gd-IgA1 u pacientov s in\u00fdmi typmi glomerulopati\u00ed (FSGS a mal\u00e9 abnormality glomerulov) sme v literat\u00fare na\u0161li \u00fadaj o asoci\u00e1cii nefrit\u00eddy a Gd-IgA1 komplexov u chor\u00fdch\u00a0 s Henochovou-Schoenleinovou purpurou a IgA1 myel\u00f3mom(10). Pacient 6 m\u00e1 v anamn\u00e9ze potravinov\u00fa alergiu, ktor\u00e1 je spojen\u00e1 s poruchou slizni\u010dnej imunity, a preto na z\u00e1klade liter\u00e1rnych \u00fadajov mo\u017eno predpoklada\u0165 aj tento \u00a0mechanizmus zv\u00fd\u0161enej produkcie Gd-IgA1(5).<\/p>\n
Pod\u013ea \u00a0Zhao \u00a0a kol. s\u00fa \u00a0vysok\u00e9 \u00a0hodnoty s\u00e9rov\u00e9ho Gd-IgA1 asociovan\u00e9 aj so zv\u00fd\u0161en\u00fdm rizikom progresie ochorenia a maj\u00fa prognostick\u00fd v\u00fdznam(9), pod\u013ea niektor\u00fdch \u0161t\u00fadi\u00ed \u00a0v\u0161ak \u00a0s\u00e9rov\u00e9 hodnoty Gd-IgA1 nekoreluj\u00fa s hodnotou protein\u00farie a s poklesom glomerulovej filtr\u00e1cie, ale percento Gd-IgA1\/celkov\u00e9 IgA koreluje \u00a0s klinick\u00fdmi faktormi \u00a0nepriaznivej progn\u00f3zy, ktor\u00fdmi s\u00fa pokles glomerulovej filtr\u00e1cie a z\u00e1va\u017enos\u0165 protein\u00farie(8).<\/p>\n
Jedn\u00fdm z cie\u013eov na\u0161ej \u0161t\u00fadie bolo interpretova\u0165 hodnoty Gd-IgA1 v skupine pacientov s IgAN po transplant\u00e1cii obli\u010dky, ktor\u00ed u\u017e\u00edvaj\u00fa imunosupres\u00edvnu lie\u010dbu. \u00a0Je dok\u00e1zan\u00e9, \u017ee imunosupres\u00edvna terapia ovplyv\u0148uje hodnoty Gd-IgA1. Kim a kol. (2016) hodnotili vplyv imunosupres\u00edvnej lie\u010dby na koncentr\u00e1cie Gd-IgA1 po 3 a 6 mesiacoch od transplant\u00e1cie, pri\u010dom po 3 mesiacoch bola \u00a0imunosupres\u00edvna lie\u010dba \u00a0redukovan\u00e1.<\/p>\n
Hodnoty \u00a0Gd-IgA1 boli signifikantne ni\u017e\u0161ie po 3 mesiacoch od transplant\u00e1cie, po redukcii \u00a0imunosupres\u00edvnej lie\u010dby boli hodnoty Gd-IgA1 po 6 mesiacoch signifikantne vy\u0161\u0161ie. \u00a0Zmeny koncentr\u00e1ci\u00ed Gd-IgA1 boli asociovan\u00e9 hlavne so zmenami v d\u00e1vkovan\u00ed predniz\u00f3nu(11). V \u010dase odberu krvn\u00fdch vzoriek na stanovenie Gd-IgA1 u\u017e\u00edvalo predniz\u00f3n 93 % pacientov v skupine 1 a 92 % pacientov v skupine 2. Priemern\u00e1 d\u00e1vka predniz\u00f3nu bola 7,5\u2008mg v oboch skupin\u00e1ch. Vy\u0161etrenie Gd-IgA1 bolo zrealizovan\u00e9 iba raz, \u010do pova\u017eujeme za nedostatok na\u0161ej \u0161t\u00fadie. Preto \u00a0u na\u0161ich pacientov nem\u00f4\u017eeme hodnoti\u0165 \u00a0vplyv redukcie d\u00e1vky predniz\u00f3nu na koncentr\u00e1ciu Gd-IgA1.<\/p>\n
Rekurencia IgAN v transplantovanej obli\u010dke po transplant\u00e1cii nie je zriedkav\u00e1. Histologick\u00e9 zn\u00e1mky rekurencie mo\u017eno n\u00e1js\u0165 a\u017e u 60 % pacientov, pri\u010dom\u00a0 25 % m\u00e1 zn\u00e1mky dysfunkcie \u0161tepu a u 5 % pacientov vedie \u00a0rekurencia IgAN k strate \u0161tepu(12). Berthelot \u00a0a kol. (2015) \u00a0potvrdili, \u017ee pacienti s rekurenciou IgAN po transplant\u00e1cii obli\u010dky mali vy\u0161\u0161ie koncentr\u00e1cie Gd-IgA1 predtransplanta\u010dne ako transplantovan\u00ed pacienti bez rekurencie a ako kontroln\u00e1 skupina pacientov(13). Pre na\u0161u anal\u00fdzu \u00a0sme nemali\u00a0 k dispoz\u00edcii \u00a0predtransplanta\u010dn\u00e9 s\u00e9ra na vy\u0161etrenie Gd-IgA1. V s\u00fabore pacientov s\u00fa dvaja pacienti s rekurenciou IgAN, ktor\u00e1 viedla k zlyhaniu \u0161tepu. T\u00edto pacienti nemali zv\u00fd\u0161en\u00e9 koncentr\u00e1cie Gd-IgA1. Niektor\u00ed autori v\u0161ak uv\u00e1dzaj\u00fa vy\u0161\u0161iu predikt\u00edvnu hodnotu ostatn\u00fdch biomarkerov, ako s\u00fa napr. \u00a0protil\u00e1tky proti Gd-IgA1 a solubiln\u00e9 CD89 komplexy. Preh\u013ead \u00a0t\u00fdchto \u00a0biomarkerov uv\u00e1dzame v tabu\u013eke 3<\/em><\/strong>.<\/p>\n
Yanagawa a kol. (2014) potvrdili signifikantne vy\u0161\u0161ie hodnoty s\u00e9rov\u00fdch anti-Gd-IgA1 IgG a IgA autoprotil\u00e1tok u pacientov s IgAN v porovnan\u00ed s pacientmi s non-IgAN chronickou obli\u010dkovou chorobou. 91 % pacientov s IgAN a norm\u00e1lnou hodnotou Gd-IgA1 malo \u00a0zv\u00fd\u0161en\u00e9 hodnoty anti-Gd-IgA1 IgG autoprotil\u00e1tok, produkcia autoprotil\u00e1tok je preto \u00a0pravdepodobne nez\u00e1visl\u00e1 od koncentr\u00e1cie Gd-IgA1.<\/p>\n
S\u00e9rov\u00e9 hodnoty anti-Gd-IgA1 IgA autoprotil\u00e1tok koreluj\u00fa s intenzitou mezangi\u00e1lnych IgA depozitov a s\u00e9rov\u00e9 hodnoty IgG autoprotil\u00e1tok s\u00fa asociovan\u00e9 s histologick\u00fdm stup\u0148om a so z\u00e1va\u017enos\u0165ou protein\u00farie(14).<\/p>\n
 <\/p>\n
Z\u00e1ver<\/strong><\/p>\n
Stanovenie diagn\u00f3zy IgAN, naj\u010dastej\u0161ej prim\u00e1rnej glomerulonefrit\u00eddy \u00a0v adolescentnom a dospelom veku, vy\u017eaduje biopsiu \u00a0obli\u010dky. V klinickej praxi s\u00fa ve\u013emi cenn\u00e9 neinvaz\u00edvne met\u00f3dy, \u00a0ktor\u00e9\u00a0 \u00a0sl\u00fa\u017eia \u00a0na \u00a0monitorovanie \u00a0aktivity \u00a0choroby a umo\u017e\u0148uj\u00fa individualizova\u0165 \u00a0lie\u010dbu \u00a0a minimalizova\u0165 jej ne\u017eiaduce \u00fa\u010dinky. V pr\u00e1ci poskytujeme liter\u00e1rny preh\u013ead potenci\u00e1lnych biomarkerov relevantn\u00fdch pre IgAN a prv\u00e9 v\u00fdsledky stanovenia Gd-IgA1 u chor\u00fdch s chronick\u00fdm nefritick\u00fdm syndr\u00f3mom a nefrotick\u00fdm syndr\u00f3mom. V\u00fdznamnej\u0161\u00ed potenci\u00e1l opisovan\u00e9ho vy\u0161etrenia mo\u017eno o\u010dak\u00e1va\u0165 pri pravidelnom dlhodobej\u0161om vy\u0161etrovan\u00ed pacientov.<\/p>\n
 <\/p>\n
 <\/p>\n
L<\/strong>I<\/strong>TER<\/strong>A<\/strong>T\u00daRA<\/strong><\/p>\n
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              1. Berthelot L, Robert T, Vuiblet V, et al. Recurrent IgA nephropathy is predicted by altered \u00a0glycosylated IgA, autoantibodies and soluble \u00a0CD 89 complexes. Kidney Int. 2015; 88(4): 815-822.<\/li>\n
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                1. Boyd J, Cheung ChK, Molyneux K, et al. An update on the pathogenesis and treatment of IgA nephropathy. Kidney International 2012; 81: 833- 84<\/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 IgA nefropatia (IgAN) je naj\u010dastej\u0161ou prim\u00e1rnou glomerulonefrit\u00eddou u adolescentov a dospel\u00fdch. Od n\u00e1stupu klinick\u00fdch pr\u00edznakov progreduje do koncov\u00e9ho \u0161t\u00e1dia obli\u010dkov\u00e9ho ochorenia 1,5 % pacientov ro\u010dne \u00a0a pribli\u017ene 25<\/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":[289],"tags":[507,503,506,508,505],"class_list":["post-1242","post","type-post","status-publish","format-standard","hentry","category-biochemistry","tag-galactose-deficient-iga1","tag-hematuria-en","tag-iga-nephropathy","tag-noninvasive-biomarkers","tag-proteinuria-en","typ_clanku-original-work"],"acf":{"abstrakt":"
                  IgA nephropathy (IgAN) is the most common primary glomerulonephritis in adolescence and adult patients and is defined as an autoimmune disease with multi-hit pathogenesis and contributing genetic and environmental fac- tors. \u00a0Galactose-deficient IgA1 plays a major role in this pathogenetic process. High serum levels of Gd-IgA1 are found in most patients with IgAN, and they are associated with poor prognosis, as confirmed by various studies. A renal biopsy \u00a0is required for accurate diagnosis, and \u00a0hence the application of noninvasive biomarkers can \u00a0be helpful in monitoring disease activity, choosing an individual approach for therapy and decreasing side \u00a0effects. In our study, \u00a0we provide \u00a0a review about noninvasive biomarkers of IgAN and the first results of Gd-IgA1 meas- urement in patients with chronic nephritic and nephrotic syndromes, increased serum Gd-IgA1 levels \u00a0were ob- served in 6 patients (7%). The difference among groups was not statistically significant.<\/p>\n
                  K<\/strong>e<\/strong>ywords<\/strong>: IgA nephropathy, galactose-deficient IgA1, noninvasive biomarkers, hematuria, proteinuria<\/p>\n","casopis":[{"ID":1223,"post_author":"7","post_date":"2017-09-26 14:15:30","post_date_gmt":"2017-09-26 12:15:30","post_content":"
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                  • Fertility disorders: immunological causes and possible curative impact<\/li>\r\n \t
                  • The first results of galactose-deficient IgA1 measurement in diagnosis and monitoring of patients with IgA nephropathy<\/li>\r\n \t
                  • Application of autovaccines in the treatment of chronic and recurrent colpitises<\/li>\r\n \t
                  • Infections of the hip endoprostheses<\/li>\r\n \t
                  • Non-invasive markers of liver fibrosis<\/li>\r\n<\/ul>","post_title":"Newslab","post_excerpt":"","post_status":"publish","comment_status":"closed","ping_status":"closed","post_password":"","post_name":"newslab-2017-2","to_ping":"","pinged":"","post_modified":"2017-09-26 14:19:35","post_modified_gmt":"2017-09-26 12:19:35","post_content_filtered":"","post_parent":0,"guid":"http:\/\/www.newslab.sk\/casopis\/newslab-2017-2\/","menu_order":0,"post_type":"casopis","post_mime_type":"","comment_count":"0","filter":"raw"}],"strana":"78","upload_clanok":{"ID":1237,"id":1237,"title":"NEWSLAB 2-2017_Oravcov\u00e1","filename":"NEWSLAB-2-2017_Oravcov\u00e1.pdf","filesize":844728,"url":"https:\/\/www.newslab.sk\/wp-content\/uploads\/2017\/09\/NEWSLAB-2-2017_Oravcov\u00e1.pdf","link":"https:\/\/www.newslab.sk\/en\/the-first-results-of-galactose-deficient-iga1-measurement-in-diagnosis-and-monitoring-of-patients-with-iga-ne-phropathy\/newslab-2-2017_oravcova-2\/","alt":"","author":"7","description":"","caption":"","name":"newslab-2-2017_oravcova-2","status":"inherit","uploaded_to":1242,"date":"2017-09-27 08:08:20","modified":"2017-09-27 08:08:20","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\/1242","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=1242"}],"version-history":[{"count":0,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/posts\/1242\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/media?parent=1242"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/categories?post=1242"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/tags?post=1242"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}