{"id":1137,"date":"2016-12-05T22:35:57","date_gmt":"2016-12-05T21:35:57","guid":{"rendered":"http:\/\/www.newslab.sk\/2016\/12\/05\/nove-autoprotilatky-v-diagnostike-autoimunitnych-myopatii\/"},"modified":"2017-10-03T14:59:14","modified_gmt":"2017-10-03T12:59:14","slug":"new-autoantibodies-in-diagnosis-of-autoimmunity-myopathies","status":"publish","type":"post","link":"https:\/\/www.newslab.sk\/en\/new-autoantibodies-in-diagnosis-of-autoimmunity-myopathies\/","title":{"rendered":"New autoantibodies in diagnosis of autoimmunity myopathies"},"content":{"rendered":"<pre><strong><span style=\"color: #ff0000;\">*All tables, charts, graphs and pictures that are featured in this article can be found in the .pdf <\/span><\/strong>\r\n <strong><span style=\"color: #ff0000;\">attachment at the end of the paper. <\/span><\/strong><\/pre>\n<p>&nbsp;<\/p>\n<ol>\n<li><strong>\u00davod<\/strong><\/li>\n<\/ol>\n<p>V\u00fdskyt autoprotil\u00e1tok v\u00a0s\u00e9re je \u010dast\u00fdm prejavom autoimunitn\u00fdch ochoren\u00ed a\u00a0najm\u00e4 syst\u00e9mov\u00fdch ochoren\u00ed spojiva. Napriek tomu, \u017ee sa niektor\u00e9 autoprotil\u00e1tky zasl\u00fa\u017eili o\u00a0objasnenie imunopatologick\u00fdch pochodov vzniku niektor\u00fdch autoimunitn\u00fdch ochoren\u00ed, ich v\u00fdznam je hlavne klinick\u00fd. Klinick\u00e9 vyu\u017eitie je najm\u00e4 diagnostick\u00e9, preto\u017ee niektor\u00e9 s\u00fa \u0161pecifick\u00e9 pre ur\u010dit\u00e9 ochorenie a\u00a0s\u00fa aj s\u00fa\u010das\u0165ou klasifika\u010dn\u00fdch krit\u00e9ri\u00ed (napr. anti-dsDNA a\u00a0anti-Sm pri syst\u00e9movom lupus erythematodes). Niektor\u00e9 autoprotil\u00e1tky s\u00fa zas asociovan\u00e9 s\u00a0klinick\u00fdmi pr\u00edznakmi, \u010do m\u00f4\u017ee by\u0165 n\u00e1pomocn\u00e9 pri odhade \u010fal\u0161ieho priebehu ochorenia,\u00a0pr\u00edpadne progn\u00f3zy a\u00a0teda prispieva aj k\u00a0rozhodovaniu oh\u013eadne sp\u00f4sobu a\u00a0agresivity lie\u010dby.<\/p>\n<p>Mnoh\u00e9 autoprotil\u00e1tky s\u00fa zn\u00e1me u\u017e pomerne dlho, je zn\u00e1my ich v\u00fdznam, m\u00f4\u017ee sa v\u0161ak meni\u0165 sp\u00f4sob ich detekcie, \u010do \u010dasto prispieva k\u00a0zvy\u0161ovaniu senzitivity. St\u00e1le sa v\u0161ak objavuj\u00fa nov\u00e9 autoprotil\u00e1tky, viac alebo menej frekventn\u00e9, \u010dasto v\u0161ak vysoko \u0161pecifick\u00e9 pre dan\u00e9 ochorenie, ktor\u00e9 m\u00f4\u017eu ve\u013emi v\u00fdrazne prispie\u0165 k\u00a0diagnostike autoimunitn\u00e9ho ochorenia. Pr\u00edkladom tak\u00fdchto ochoren\u00ed, u ktor\u00fdch bola v\u00a0posledn\u00fdch rokoch pop\u00edsan\u00e1 asoci\u00e1cia s\u00a0nov\u00fdmi autoprotil\u00e1tkami s\u00fa idiopatick\u00e9 z\u00e1palov\u00e9 myopatie (IIM), a to hlavne polymyozit\u00edda (PM) a\u00a0dermatomyozit\u00edda (DM). U\u00a0myozit\u00edd rozli\u0161ujeme autoprotil\u00e1tky pre myozit\u00eddy \u0161pecifick\u00e9 (myositis specific antibodies-MSA), ktor\u00e9 sa nevyskytuj\u00fa pri\u00a0\u017eiadnych in\u00fdch autoimunitn\u00fdch ochoreniach, ako napr. protil\u00e1tky proti aminoacyl-tRNA syntet\u00e1zam (anti-ARS), naj\u010dastej\u0161ie anti-Jo-1 (proti histidyl-tRNA syntet\u00e1ze), anti-SRP (proti \u201esignal recognition particle\u201c) a\u00a0proti antig\u00e9nu Mi-2 (\u201cnuclear helicase protein, part of NuRD complex\u201c) a protil\u00e1tky s\u00a0myozit\u00eddou asociovan\u00e9 (myositid associated antibodies-MAA), napr. anti-Ro52, anti-PM\/Scl, anti-Ku (\u201cDNA-binding, non-histone protein\u201c) \u010di anti-U1RNP, ktor\u00e9 sa m\u00f4\u017eu vyskytova\u0165 aj pri in\u00fdch syst\u00e9mov\u00fdch ochoreniach ako s\u00fa IIM, m\u00f4\u017eu v\u0161ak by\u0165 n\u00e1pomocn\u00e9 pri definovan\u00ed podtypov ochorenia (tab.1). Popri t\u00fdchto zn\u00e1mych autoprotil\u00e1tkach bolo v\u00a0posledn\u00fdch nieko\u013ek\u00fdch rokoch pop\u00edsan\u00fdch minim\u00e1lne osem nov\u00fdch autoprotil\u00e1tok \u0161pecifick\u00fdch pre IIM. V\u00a0na\u0161om pr\u00edspevku sa pok\u00fasime poda\u0165 stru\u010dn\u00fd preh\u013ead, charakteristiku a\u00a0klinick\u00fd v\u00fdznam t\u00fdchto novo identifikovan\u00fdch protil\u00e1tok.<\/p>\n<p>&nbsp;<\/p>\n<ol start=\"2\">\n<li><strong>Nov\u00e9 autoprotil\u00e1tky<\/strong><\/li>\n<\/ol>\n<p><strong>Anti-aminoacyl-tRNA syntet\u00e1zov\u00e9 (ARS) protil\u00e1tky <\/strong><\/p>\n<p>Aminoacyl-tRNA syntet\u00e1zy (ARS) s\u00fa enz\u00fdmy katalyzuj\u00face v\u00e4zbu aminokysel\u00edn k\u00a0tRNA, rozozn\u00e1vame preto 20 typov ARS. ARS s\u00fa aj jedn\u00fdm z\u00a0hlavn\u00fdch antig\u00e9nov\u00fdch ter\u010dov pri myozit\u00edach, a\u00a0protil\u00e1tky proti nim namieren\u00e9 s\u00fa naj\u010dastej\u0161ie sa vyskytuj\u00face tak pri PM ako aj DM. Doned\u00e1vna bolo identifikovan\u00fdch 6 autoprotil\u00e1tok reaguj\u00facich s\u00a0r\u00f4znymi tRNA syntet\u00e1zami: anti-Jo-1 (histidyl), anti-PL-7 (treonyl), anti-PL-12 (alanyl), anti-OJ (isolecyl), anti-EJ (glycyl) a\u00a0anti-KS (asparaginyl-tRNA syntet\u00e1za). A\u017e na mal\u00e9 v\u00fdnimky sa u\u00a0jedn\u00e9ho pacienta vyskytuje v\u017edy len jedna z\u00a0t\u00fdchto autoprotil\u00e1tok, av\u0161ak pacienti napriek tomu vykazuj\u00fa podobn\u00e9 klinick\u00e9 pr\u00edznaky, ktor\u00e9 sa spolo\u010dne naz\u00fdvaj\u00fa tzv. antisyntet\u00e1zov\u00fd syndr\u00f3m (ASS) (1). V\u00a0posledn\u00fdch rokoch boli pop\u00edsan\u00e9 autoprotil\u00e1tky proti \u010fal\u0161\u00edm tRNA syntet\u00e1z\u00e1m, ktor\u00fdch v\u00fdskyt je s\u00edce extr\u00e9mne n\u00edzky, \u0161pecificita v\u0161ak, podobne ako u\u00a0ostatn\u00fdch ARS ve\u013emi vysok\u00e1:<\/p>\n<ul>\n<li><strong>anti-fenylalanyl-tRNA-syntet\u00e1za (anti-Zo)<\/strong> bola pop\u00edsan\u00e1 Betterdgeom a\u00a0kol. v\u00a0roku 2007 u\u00a0pacienta s\u00a0interstici\u00e1lnou pneum\u00f3niou spojenou s proxim\u00e1lnou myopatiou, Raynaudovym fenom\u00e9non and arthralagiou. Imunofluorescen\u010dne na Hep2 bunk\u00e1ch pozorovali\u00a0siln\u00fa pozitivitu\u00a0 zrnitej cytoplazmy, n\u00e1sledne sa v\u0161ak nepodarilo dok\u00e1za\u0165 pr\u00edtomnos\u0165 \u017eiadneho zn\u00e1meho antig\u00e9nu. Imunoprecipit\u00e1ciou autori dok\u00e1zali pr\u00edtomnos\u0165 dvoch prote\u00ednov s\u00a0molekulovou hmotnos\u0165ou pribli\u017ene 60 a\u00a070 kDa a n\u00e1slednou kombin\u00e1ciou imunoprecipit\u00e1cie a\u00a0hmotnostnej spektrometrie identifikovali ter\u010dov\u00fd \u00a0antig\u00e9n ako phenylalanyl-tRNA syntet\u00e1zu (2)<\/li>\n<li><strong>anti-ty<\/strong><strong>rosyl-tRNA syntet\u00e1za (anti-YRS)<\/strong> protil\u00e1tky pop\u00edsal Hashish v\u00a0roku 2005 u\u00a0pacienta s\u00a0ASS, tieto protil\u00e1tky boli zatia\u013e objaven\u00e9 len u\u00a0jedn\u00e9ho pacienta, zara\u010fujeme ich preto ku skupine vz\u00e1cnych ARS (3).<\/li>\n<li><strong>anti-asparaginyl-tRNA syntet\u00e1za (anti-AsnRS)<\/strong> protil\u00e1tky boli pop\u00edsan\u00e9 Hirakatom a\u00a0kol. v\u00a0roku 2007. Autori analyzovali 2500 s\u00e9r pacientov s\u00a0r\u00f4znymi ochoreniami spojiva, pozitivitu anti-AsnRS dok\u00e1zali u\u00a08 pacientov, pri\u010dom a\u017e 4 z\u00a0nich mali ILD, av\u0161ak len dvaja DM, v\u00fdskyt anti-AsnRS je preto asociovan\u00fd sk\u00f4r s\u00a0ILD ako s\u00a0DM. Imunogenetickou anyl\u00fdzou sa navy\u0161e autorom podarila dok\u00e1za\u0165 asoci\u00e1ciu anti-AsnRS s DRB1*1501\/1502 alelou (4).<\/li>\n<\/ul>\n<p><strong>\u00a0<\/strong><\/p>\n<p><strong>Anti-CADM-140 (anti-MDA5) protil\u00e1tky<\/strong><\/p>\n<p>Amyopatick\u00e1 dermatomyozit\u00edda (clinically amyopathic DM-CADM) je charakterizovan\u00e1 ako ochorenie s\u00a0typick\u00fdmi ko\u017en\u00fdmi prejavmi DM, av\u0161ak bez pr\u00edznakov svalovej slabosti. Asi u 10 % t\u00fdchto pacientov d\u00f4jde nieko\u013eko mesiacov a\u017e rokov po vzniku ko\u017en\u00fdch pr\u00edznakov aj ku klinick\u00fdm prejavom myozit\u00eddy. U \u010fal\u0161\u00edch 10 % pacientov do 6 mesiacov od vzniku ko\u017en\u00fdch zmien doch\u00e1dza k manifest\u00e1cii potenci\u00e1lne fat\u00e1lnej p\u013e\u00facnej fibr\u00f3zy (interstitial lung disease-ILD) bez ak\u00fdchko\u013evek pr\u00edznakov myozitick\u00e9ho postihnutia (5). Doned\u00e1vna sa predpokladalo, \u017ee u amyotickej dermatomyozit\u00eddy na nevyskytuj\u00fa \u017eiadne MSA protil\u00e1tky, \u010do bolo pova\u017eovan\u00e9 za charakteristick\u00fa \u010drtu tohto ochorenia. V\u00a0roku 2005 Sato a\u00a0kol. (6) prv\u00fdkr\u00e1t pop\u00edsali u\u00a0pacientov s amyopatickouj dermatomyozit\u00eddy pr\u00edtomnos\u0165 \u0161pecifick\u00fdch protil\u00e1tok, ktor\u00e9 precipitovali so 140 kDa prote\u00ednom, boli teda nazvan\u00e9 anti-CADM-140. Testovali 298 s\u00e9r pacientov s\u00a0r\u00f4znymi ochorenia spojiva, anti-CADM-140 dok\u00e1zali u\u00a08 zo 42 pacientov s\u00a0DM, av\u0161ak ani u\u00a0jedn\u00e9ho pacienta s\u00a0in\u00fdm ochoren\u00edm, pri\u010dom v\u0161etci 8 pacienti mali amyopatick\u00fa dermatomyozit\u00eddu (CADM) a\u00a0navy\u0161e pacienti anti-CADM-140 pozit\u00edvni rozvinuli r\u00fdchlej\u0161ie progres\u00edvnu ILD oproti pacientom anti-CADM-140 negat\u00edvnym. <strong><em>\u00a0<\/em><\/strong>Nakashima a\u00a0kol. (7) vo svojej \u0161t\u00fadii z\u00a0roku 2010 testovali\u00a0 192 s\u00e9r pacientov s\u00a0r\u00f4znymi ochoreniami spojiva, z\u00a0nich PM=47 , DM=37 a\u00a0CADM=1. U\u00a013 pacientov bola dok\u00e1zan\u00e1 pr\u00edtomnos\u0165 anti-CADM-140 protil\u00e1tok, v\u0161etci pacienti pozit\u00edvni na pr\u00edtomnos\u0165 anti-CADM-140 protil\u00e1tok mali DM (typick\u00fa alebo amyopatick\u00fa), naviac ani u\u00a0jedn\u00e9ho z\u00a0t\u00fdchto pacientov nebola dok\u00e1zan\u00e1 pr\u00edtomnos\u0165 in\u00fd MSA alebo MAA protil\u00e1tok.\u00a0 Z\u00a013 anti-CADM-140 pozit\u00edvnych pacientov 92% malo ILD (54% rozvinulo fat\u00e1lnu ILD). Klinick\u00e1 progn\u00f3za DM pacientov pozit\u00edvnych na anti-CADM-140 bola hor\u0161ia oproti DM pacientom anti-CADM-140 negat\u00edvnym, 46% anti-CADM-140 pozit\u00edvnych pacientov zomrelo na respira\u010dn\u00e9 zlyhanie do 6 mesiacov od prepuknutia ochorenia. Nakashima a\u00a0kol. v\u00a0tejto \u0161t\u00fadii identifikovali aj autoantig\u00e9n anti-CADM-140 protil\u00e1tok, ktor\u00fdm je \u201ethe melanoma differentiation-associated Gene 5\u201c (MDA5), ktor\u00fd hr\u00e1 v\u00fdznamn\u00fa \u00falohu vo vrodenej imunitnej odpovedi svojou schopnos\u0165ou interakcie s v\u00edrusovou RNA. Toto zistenie m\u00f4\u017ee podporova\u0165 doteraj\u0161ie predpoklady vz\u0165ahu myozit\u00eddy a v\u00edrusovej infekcie (hlavne Coxakie infekcie). Na potvrdenie tejto te\u00f3rie je v\u0161ak treba dok\u00e1za\u0165, \u010di\u00a0 anti\u2013CADM-140 a MDA5 hraj\u00fa patogenetick\u00fa \u00falohu v rozvoji DM.<\/p>\n<p>Nesk\u00f4r bola pr\u00edtomnos\u0165 anti-CADM-140 dok\u00e1zan\u00e1 na viacer\u00fdch s\u00faboroch pacientov, pri\u010dom najvy\u0161\u0161ia prevalencia anti-CADM-140 protil\u00e1tok u\u00a0DM pacientov bola doteraz zaznamenan\u00e1 v\u00a0Japonsku (25%-35%)\u00a0 (8). Retrospekt\u00edvne \u0161t\u00fadie dok\u00e1zali pr\u00edtomnos\u0165 anti-CADM-140 protil\u00e1tok aj u\u00a0eur\u00f3pskych pacientov (13% DM pacientov), pri\u010dom bola dok\u00e1zan\u00e1 ich korel\u00e1cia s \u0165a\u017ek\u00fdmi formami r\u00fdchlo progreduj\u00facej ILD a\u00a0zlou klinickou progn\u00f3zou pacientov (9,10).<\/p>\n<p><strong><em>\u00a0<\/em><\/strong><\/p>\n<p><strong>Anti-p155(\/p140) (anti-<\/strong><strong>TIF1-\u03b3) protil\u00e1tky<\/strong><\/p>\n<p>Asoci\u00e1cia myopati\u00ed, hlavne dermazomyzozit\u00eddy s\u00a0praneoplastick\u00fdmi ochoreniami je dobre zn\u00e1ma u\u017e nieko\u013eko desa\u0165ro\u010d\u00ed, preto je u\u00a0t\u00fdchto pacientov odpor\u00fa\u010dan\u00fd skr\u00edning paraneoplastick\u00fdch ochoren\u00ed. A\u017e doned\u00e1vna, v\u0161ak nebol zn\u00e1my marker, ktor\u00fd by bol na tak\u00fdto skr\u00edning vhodn\u00fd. V\u00a0roku 2006 Targoff a\u00a0kol. (11) ako prv\u00ed pop\u00edsali u\u00a0pacientov s\u00a0DM nov\u00fa protil\u00e1tku, rozozn\u00e1vaj\u00facu 155 kDa prote\u00edn a\u00a0155\/140 kD doublet (anti-p155\/140), ktorej ter\u010dov\u00fdm antig\u00e9nom je \u201etranscription intermediary factor 1-gamma\u201c (TIF1-\u03b3) a ktor\u00e1 vykazuje siln\u00fa korel\u00e1ciu s\u00a0DM a\u00a0malignitami. Pr\u00edtomnos\u0165 anti-p155 (TIF1-\u03b3) protil\u00e1tok dok\u00e1zali u\u00a051 z\u00a0244 sledovan\u00fdch pacientov s\u00a0myozit\u00eddou (21%), u\u00a0jedn\u00e9ho zo\u00a049 pacientov so SLE av\u0161ak u\u00a0\u017eiadneho bez myozit\u00eddy. Vo svojej \u0161t\u00fadii s\u00fa\u010dasne uk\u00e1zali siln\u00fa imunogenetick\u00fa asoci\u00e1ciu anti-p155\/140 s\u00a0rizikovou alelou DQA1*0301 v kaukazoidnej popul\u00e1cii. Takmer s\u00fa\u010dasne s Targoffom dok\u00e1zal pr\u00edtomnos\u0165 anti-p155\/140 protil\u00e1tok Kaji so spolupracovn\u00edkmi (12), ktor\u00ed dok\u00e1zali u 13% pacientov s DM protil\u00e1tky anti-p155\/140 (TIF1-\u03b3), pri\u010dom a\u017e u 71% anti-p155\/140 pozit\u00edvnych pacientov s DM zaznamenali pr\u00edtomnos\u0165 malign\u00edt. Vysok\u00e1 asoci\u00e1cia anti-p155\/140 (TIF1-\u03b3) protil\u00e1tok s malignitami u pacientov s DM a mo\u017enos\u0165 ich vyu\u017eiatia ako skr\u00edningov\u00e9ho markera pre vyh\u013ead\u00e1vanie malign\u00edt u t\u00fdchto pacientov, bola n\u00e1sledne potvrden\u00e1 viacer\u00fdmi \u0161t\u00fadiami (13, 14). Horrilo so spolupracovn\u00edkmi na z\u00e1klade svojej \u0161t\u00fadie, v\u00a0ktorej porovnali viacer\u00e9 met\u00f3dy detekcie anti-p155\/140 protil\u00e1tok s\u00a0ve\u013emi dobrou zhodou,\u00a0 odpor\u00fa\u010daj\u00fa zavies\u0165 anti-p155\/140 (TIF1-\u03b3) do laborat\u00f3rnej praxe ako marker v\u00fdskytu malign\u00edt u\u00a0pacientov s\u00a0DM (15). Z metatanal\u00fdzy, ktor\u00fa publikoval Trallero-Araguas vypl\u00fdva, \u017ee pozitivita anti-p155 protil\u00e1tok predstavuje 89% \u0161pecificitu a 78% senzitivitu pre diagn\u00f3zu malignity asociovanej s DM, s\u00a0pozit\u00edvnou a negat\u00edvnou predikt\u00edvnou hodnotou 58 resp. 95% (16).<\/p>\n<p><strong><em>\u00a0<\/em><\/strong><\/p>\n<p><strong>Anti-NXP-2 (anti-MJ) protil\u00e1tky<\/strong><\/p>\n<p>Anti-MJ protil\u00e1tky, boli prv\u00fdkr\u00e1t pop\u00edsan\u00e9 u\u00a018% pacientov s\u00a0juvenilnou dermatomyozit\u00eddou (JDM) (17), nesk\u00f4r bol pop\u00edsan\u00fd ich antig\u00e9nov\u00fd ter\u010d, ktor\u00fdm je \u201enuclear matrix protein 2\u201c (NXP-2), a ich v\u00fdskyt u pacientov s JDM bol dok\u00e1zan\u00fd vo viacer\u00fdch \u0161t\u00fadia\u00e1ch s v\u00fdskytom 23-25%. Gunawardena so spolupracovn\u00edkmi dok\u00e1zal pr\u00edtomnos\u0165 anti-NXP-2 protil\u00e1tok u 23% pacientov s JDM, av\u0161ak u \u017eiadneho pacienta s JDM overlap syndr\u00f3mom ani v kontrolnej skupine. Vo svojej pr\u00e1ci navy\u0161e dak\u00e1zali pr\u00edtomnos\u0165 alely HLA-DRB1*08 ako mo\u017en\u00e9ho rizikov\u00e9ho faktora pre pozitivitu anti-NXP-2 protil\u00e1tok (18). V\u00a0skupine argent\u00ednskych pacientov s\u00a0JDM bol v\u00fdskyt anti-NXP-2 protil\u00e1tok (25%) podobn\u00fd ako v skupine pacientov z\u00a0Ve\u013ekej Brit\u00e1nie a\u00a0podobne ako v\u00a0tejto skupine aj s\u00a0vysokou incidenciou (19). Na z\u00e1klade t\u00fdchto \u0161t\u00fadi\u00ed sa predpokladalo, \u017ee v\u00fdskyt anti-NXP-2 je asociovan\u00fd len s\u00a0JDM, av\u0161ak Betteridge a\u00a0kol. detegovali anti-NXP-2 aj v\u00a0skupine dospel\u00fdch pacientov s\u00a0DM, napriek tomu, \u017ee ich v\u00fdskyt je ove\u013ea ni\u017e\u0161\u00ed (6% pacientov s\u00a0DM) (20). V\u00a0dvoch \u010fal\u0161\u00edch \u0161t\u00fadi\u00e1ch bol v\u00fdskyt anti-NXP-2 u\u00a0dospel\u00fdch DM pacientov ve\u013emi rozdielny. V\u00a0talianskej \u0161t\u00fadii 58 pacientov s IIM boli anti-NXP-2 protil\u00e1tky detegovan\u00e9\u00a0 u 30% DM a 8% PM pacientov, v\u00fdskyt protil\u00e1tok bol pritom asociovan\u00fd s\u00a0mlad\u00fdm vekom a\u00a0dobrou odpove\u010fou na terapiu, zatia\u013e \u010do v\u00a0japonskej skupine 507 dospel\u00fdch pacientov boli anti-NXP-2 detegovan\u00e9 len u\u00a01,6% DM ako aj 1,6% pacientov s\u00a0PM. V\u0161etci anti-NXP-2 pozit\u00edvni pacienti mali signifikantn\u00e9 bolesti svalov a\u00a0zv\u00fd\u0161en\u00e9 hodnoty kretin\u00edn kin\u00e1zy,\u00a0u\u00a038% sa do 3 rokov od stanovenia diagn\u00f3zy polymozit\u00eddy objavilo mal\u00edgne ochorenie. Aby sme mohli poveda\u0165, \u010di s\u00fa rozdielne v\u00fdsledky medzi \u0161tudovan\u00fdmi skupinami v\u00fdsledkom r\u00f4znych detek\u010dn\u00fdch met\u00f3d stanovenia protil\u00e1tok, alebo ide o\u00a0vplyv popula\u010dno-genetick\u00fdch aspektov, pr\u00edpadne vplyv prostredia, bude treba \u010fal\u0161ie \u0161t\u00fadie s v\u00e4\u010d\u0161\u00edm po\u010dtom pacientov (21,22).<\/p>\n<p>&nbsp;<\/p>\n<p><strong>Anti-SAE protil\u00e1tky<\/strong><\/p>\n<p>Anti-SAE \u201esmall ubiquitin-like modifier activating enzyme\u201c protil\u00e1tky boli prv\u00fdkr\u00e1t dentifikovan\u00e9 Betteridgeom a\u00a0kol. v\u00a0roku 2007 a v\u00a0roku 2009 tou istou skupinou potvrden\u00e9 na v\u00e4\u010d\u0161ej skupine IIM pacientov. Cie\u013eov\u00fdm antig\u00e9nom anti-SAE protil\u00e1tok je\u00a0\u00a0 \u201eSmall Ubiquitin-like MOdifier (SUMO) activating enzyme\u201c, ktor\u00fd sa sklad\u00e1 z\u00a0dvoch podjednotiek SAE1 a\u00a0SAE2, s\u00a0molekulovou hmostnos\u0165ou 40a 90 kDa. SUMO je mal\u00fd prote\u00edn \u0161trukt\u00farne podobn\u00fd ubiquit\u00ednu a hr\u00e1 k\u013e\u00fa\u010dov\u00fa \u00falohu v\u00a0posttransla\u010dnej \u00faprave \u0161pecifick\u00fdch prote\u00ednov ako napr. prote\u00edn kin\u00e1za a\u00a0transkrip\u010dn\u00e9 faktory. Autori vo svojej\u00a0\u0161t\u00fadii zistili pr\u00edtomnos\u0165 anti-SAE protil\u00e1tok u\u00a08% dospel\u00fdch pacientov s\u00a0DM, av\u0161ak ani u\u00a0jedn\u00e9ho s\u00a0in\u00fdm ochoren\u00edm, ani u\u00a0zdrav\u00fdch jedincov. V\u00a0pr\u00e1ci z\u00a0roku 2009 Betteridge a\u00a0kol. tie\u017e identifikovali imunogenetick\u00fa asoci\u00e1ciu medzi produkciou anti-SAE protil\u00e1tok a\u00a0HLA syst\u00e9mom. V\u0161etci anti-SAE pozit\u00edvni pacienti exprimovali aspo\u0148 jednu k\u00f3piu alely HLA-DQB1*03 a HLA-DRB1*04-DQA1*03-DQB1*03, pr\u00edtomnos\u0165 t\u00fdchto aliel je teda vysoko rizikov\u00fdm faktorom (23). Talianski autori na skupine 183 pacientov dok\u00e1zali pr\u00edtomnos\u0165 anti-SAE protil\u00e1tok u\u00a07% pacientov s\u00a0DM, \u010d\u00edm potvrdili anti-SAE ako protil\u00e1tky \u0161pecifick\u00e9 pre DM.. Pacienti anti-SAE pozit\u00edvni trpeli hlavne na ko\u017en\u00e9 a\u00a0svalov\u00e9 prejavy DM, na druhej strane dysf\u00e1gie, ILD a artrit\u00edda sa u\u00a0nich zv\u00e4\u010d\u0161a nevyskytovali (24). Na druhej strane japonsk\u00ed autori potvrdili pr\u00edtomnos\u0165 anti-SAE protil\u00e1tok len u\u00a02 zo 110 (1,8%) sledovan\u00fdch pacientov s\u00a0DM,\u00a0 ani jeden nemal amyotick\u00fa alebo juveniln\u00fa DM (25). Na z\u00e1klade uveden\u00fdch publik\u00e1cii m\u00f4\u017eeme anti-SAE protil\u00e1tky pova\u017eova\u0165 za \u0161pecifick\u00fd marker pre DM.<\/p>\n<p><strong>Anti-200\/100 (<\/strong><strong>anti-HMGCR) protil\u00e1tky<\/strong><\/p>\n<p>Pomerne ned\u00e1vno boli u\u00a0pacientov s\u00a0nekrotizuj\u00facou myopatiou pop\u00edsan\u00e9 nov\u00e9 autoprotil\u00e1tky. Christopher-Stine a\u00a0kol. vo svojej \u0161t\u00fadii z\u00a0roku 2010 (26) testovali u 225 pacientov s\u00a0myozyt\u00eddou s\u00fa\u010dasne vzorky biopsie svalov a\u00a0autoprotil\u00e1tky v s\u00e9re. \u00a0U\u00a038 pacientov bola histologicky dok\u00e1zan\u00e1 nekr\u00f3za myofybr\u00edl, pri\u010dom u\u00a026 z\u00a0t\u00fdchto pacientov neboli dok\u00e1zan\u00e9 \u017eiadne zn\u00e1me autoprotil\u00e1tky. Imunoprecipit\u00e1ciou boli v\u00a016 s\u00e9rach t\u00fdchto pacientov objaven\u00e9 nov\u00e9 autoprotil\u00e1tky, ktor\u00e9 reagovali s\u00a0200 a 100 kDa prote\u00ednmi (anti-200\/100 protil\u00e1tky), zo zvy\u0161n\u00fdch 187 s\u00e9r pacientov bez nekr\u00f3zy myofybr\u00edl boli tieto protil\u00e1tky zachyten\u00e9 len u\u00a0jedn\u00e9ho pacienta. Zauj\u00edmav\u00fdm zisten\u00edm bolo tie\u017e, \u017ee a\u017e u\u00a063% z\u00a0t\u00fdchto pacientov boli pred prepuknut\u00edm svalov\u00fdch bolest\u00ed pod\u00e1van\u00e9 stat\u00edny, \u010do je signifikantne viac oproti ostatn\u00fdm pacientom s\u00a0DM (15,2%), pr\u00edpadne PM (18,4%). Autori teda charakterizuj\u00fa anti-200\/100 ako protil\u00e1tky asociovan\u00e9 so stat\u00ednmi indukovanou nekrotizuj\u00facou myopatipou. Nesk\u00f4r bol tou istou skupinou autorov (27) identifikovan\u00fd ter\u010dov\u00fd antig\u00e9n anti-200\/100 protil\u00e1tok, ktor\u00fdm je \u201e3-hydroxy-3-methylglutaryl-coenzyme A reductase\u201c (HMGCR) a bola zistetn\u00e1 aj imunogenetick\u00e1 asoci\u00e1cia produkcie anti-HMGCR s HLA syst\u00e9mom,\u00a0 kde sa alela DRB1*11:01 jav\u00ed ako vysoko asociovan\u00e1 s anti-HMGCR myopatiou a\u00a0to bez vplyvu etnickej skupiny. Tieto v\u00fdsledky napovedaj\u00fa o\u00a0vz\u0165ahu medzi expoz\u00edciou stat\u00ednmi, zv\u00fd\u0161enou expresiou HMGCR a prezent\u00e1ciou HMGC- peptidov alelou DRB1*11:01. Napriek tomu, \u017ee mechanizmus vzniku a\u00a0rozvoja anti-HMGCR autoimunity nie je zn\u00e1my, vieme, \u017ee expresia HMGCR prote\u00ednov je up-regulovan\u00e1 v\u00a0bunkov\u00fdch kult\u00farach vystaven\u00fdch stat\u00ednom, HMGCR prote\u00edny s\u00fa exprimovan\u00e9 v\u00a0n\u00edzkych koncentrci\u00e1ch v norm\u00e1lnych svaloch, av\u0161ak vo vysok\u00fdch v bioptick\u00fdch vzork\u00e1ch regeneruj\u00facich svalov pacientov s HMGCR-asociovanou nekrotizuj\u00facou myopatiou. Tieto poznatky napovedaj\u00fa, \u017ee anti-HMGCR myopatia m\u00f4\u017ee by\u0165 u\u00a0geneticky predisponovan\u00fdch jedincov iniciovan\u00e1 nadexpresiou HMGCR v\u00a0s\u00favislosti s\u00a0u\u017e\u00edvan\u00edm stat\u00ednov a\u00a0pokra\u010duje (po\u010das pod\u00e1vania stat\u00ednov) v\u00a0d\u00f4sledku zv\u00fd\u0161en\u00fdch hodn\u00f4t HMGCR v\u00a0regeneruj\u00facich svalov\u00fdch bunk\u00e1ch, ktor\u00e9 sa st\u00e1vaj\u00fa ter\u010dom imunitn\u00e9ho syst\u00e9mu. Tento koncept HMGCR-myopatie v\u0161ak e\u0161te vy\u017eaduje experiment\u00e1lne potvrdenie (28).<\/p>\n<p><strong><em>\u00a0<\/em><\/strong><\/p>\n<ol start=\"3\">\n<li><strong>Klinick\u00e9 vyu\u017eitie a\u00a0z\u00e1ver<\/strong><\/li>\n<\/ol>\n<p>V\u00a0na\u0161om pr\u00edspevku sme sa sna\u017eili urobi\u0165 stru\u010dn\u00fd preh\u013ead nov\u00fdch autoprotil\u00e1tok a\u00a0ich antig\u00e9nov\u00fdch ter\u010dov, ktor\u00e9 boli pop\u00edsan\u00e9 pri autoimunitn\u00fdch myopati\u00e1ch v\u00a0posledn\u00fdch rokoch. Ide hlavne o\u00a0MSA autoprotil\u00e1tky, ktor\u00fdch prevalencia s\u00edce nemus\u00ed by\u0165 vysok\u00e1, av\u0161ak \u0161pecificita pre dan\u00e9 ochorenie sa jav\u00ed ve\u013emi vysok\u00e1. Podstatn\u00fdm poznatkom je, \u017ee sa vo v\u00e4\u010d\u0161ine pr\u00edpadov nestret\u00e1vame s\u00a0prekr\u00fdvan\u00edm t\u00fdchto protil\u00e1tok u\u00a0jedn\u00e9ho pacienta, aj preto je odpor\u00fa\u010dan\u00e9 testova\u0165 ich v\u017edy paralelne. \u010co je ale najpodstatnej\u0161ie, napriek tomu, \u017ee za zlat\u00fd \u0161tandard detekcie autoprotil\u00e1tok pri autoimunitn\u00fdch myopati\u00e1ch m\u00f4\u017ee by\u0165 pova\u017eovan\u00e1 imunoprecipit\u00e1cia, st\u00e1le r\u00fdchlej\u0161ie sa do klinickej praxe dost\u00e1vaj\u00fa aj in\u00e9 detek\u010dn\u00e9 syst\u00e9my (ELISA, Imunoblot), ktor\u00fdch senzitivita a\u00a0\u0161pecificita je porovnate\u013en\u00e1 s\u00a0imunoprecipit\u00e1ciou a\u00a0d\u00f4kaz nov\u00fdch autoprotil\u00e1tok sa preto postupne st\u00e1va s\u00fa\u010das\u0165ou klinickej imunologickej diagnostiky autoimunitn\u00fdch myopati\u00ed. V\u00a0s\u00fa\u010dasnosti u\u017e vieme, okrem protil\u00e1tok anti-HMGCR, stanovi\u0165 v\u0161etky z\u00a0uveden\u00fdch nov\u00fdch autoprotil\u00e1tok imunoblotom, pri\u010dom sa predpoklad\u00e1, \u017ee aj anti-HMGCR sa \u010doskoro stan\u00fa s\u00fa\u010das\u0165ou rutinnej imunologickej diagnostiky.<\/p>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>*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. &nbsp; \u00davod V\u00fdskyt autoprotil\u00e1tok v\u00a0s\u00e9re je \u010dast\u00fdm prejavom autoimunitn\u00fdch ochoren\u00ed a\u00a0najm\u00e4 syst\u00e9mov\u00fdch ochoren\u00ed spojiva. Napriek tomu, \u017ee sa niektor\u00e9 autoprotil\u00e1tky zasl\u00fa\u017eili o\u00a0objasnenie imunopatologick\u00fdch pochodov vzniku niektor\u00fdch autoimunitn\u00fdch ochoren\u00ed, ich v\u00fdznam<\/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":[537,739,741,740],"class_list":["post-1137","post","type-post","status-publish","format-standard","hentry","category-imunology","tag-autoantibodies","tag-autoantigens","tag-dermatomyositis","tag-myositis","typ_clanku-review-article"],"acf":{"abstrakt":"<p>Autoantibodies to various cellular constituents are detected in the sera of patients with idiopathic inflammatory myopathy (IIM). The sera are closely associated with characteristic clinical manifestations of the diseases. Therefore, autoantibodies give us a\u00a0lot of information on clinical diagnosis, classification, prediction of prognosis and choice of treatment in patients with IIM. During the last decade, novel myositis (MSA)-specific autoantibodies have been identified, such as anti-CADM-140, anti-p155, anti-NXP-2, anti-SAE and anti-200\/100, all of which, except for anti-200\/100 are dermatomyositis-specific autoantibodies. The anti-CADM-140 antibodies are associated with clinically amyopathic dermatomyositis and acute progressive interstitial pneumonia. Anti-p155 are identified in malignancy-associated myositis while anti-200\/100 are associated with necrotizing myositis. Target autoantigens have also been identified and in some cases their pathogenic role in IIM has been suggested. Better understanding of autoantigenic properties of these targeted proteins will help us to reveal the pathophysiology of IIM or its complications, and may lead to better and more efficient therapy.<\/p>\n<p>&nbsp;<\/p>\n<p><strong>Key words<\/strong>: autoantibodies, autoantigens, myositis, dermatomyositis.<\/p>\n","casopis":[{"ID":1000,"post_author":"7","post_date":"2015-11-21 14:33:24","post_date_gmt":"2015-11-21 13:33:24","post_content":"<h4><strong>GENETICS<\/strong><\/h4>\r\n<ul>\r\n \t<li>The laboratory age<\/li>\r\n \t<li>The Odyssey of DNA reading<\/li>\r\n \t<li>Comparative genomic hybridisation: a methodological introduction<\/li>\r\n \t<li>Next generation sequencing and its application in clinical genetics<\/li>\r\n<\/ul>\r\n<h4><\/h4>\r\n<h4><strong>BIOCHEMISTRY<\/strong><\/h4>\r\n<ul>\r\n \t<li>Determining of the trace elements in blood serum<\/li>\r\n \t<li>Determining of \u03b1-tocopherol (vitamin E) in serum by way of liquid chromatography with tandem mass spectrometry (LC\/MS\/MS)<\/li>\r\n \t<li>Analysis of urinary calculi and its path to Europe<\/li>\r\n<\/ul>\r\n&nbsp;\r\n<h4><strong>IMMUNOLOGY <\/strong><\/h4>\r\n<ul>\r\n \t<li>New autoantibodies in diagnosis of autoimmunity myopathies<\/li>\r\n \t<li>Taking advantage of flow-based cytometry in determining prognostic markers<\/li>\r\n<\/ul>\r\nCD38 and ZAP-70 in patients with B-CLL\r\n\r\n&nbsp;\r\n<h4><strong>CYTOLOGY AND PATHOLOGY <\/strong><\/h4>\r\n<ul>\r\n \t<li>Mucinous ovarian carcinoma \u2013 news in diagnosis from the pathologist\u2019s perspective<\/li>\r\n<\/ul>","post_title":"newsLab","post_excerpt":"","post_status":"publish","comment_status":"closed","ping_status":"closed","post_password":"","post_name":"newslab-12015","to_ping":"","pinged":"","post_modified":"2017-08-16 21:43:10","post_modified_gmt":"2017-08-16 19:43:10","post_content_filtered":"","post_parent":0,"guid":"http:\/\/www.newslab.sk\/casopis\/newslab-12015\/","menu_order":0,"post_type":"casopis","post_mime_type":"","comment_count":"0","filter":"raw"}],"strana":"34","upload_clanok":{"ID":1138,"id":1138,"title":"medirex_1_2015-tibenska","filename":"MEDIREX_1_2015-\u2013-Tibenska.pdf","filesize":157990,"url":"https:\/\/www.newslab.sk\/wp-content\/uploads\/2016\/12\/MEDIREX_1_2015-\u2013-Tibenska.pdf","link":"https:\/\/www.newslab.sk\/en\/new-autoantibodies-in-diagnosis-of-autoimmunity-myopathies\/medirex_1_2015-tibenska\/","alt":"","author":"7","description":"","caption":"","name":"medirex_1_2015-tibenska","status":"inherit","uploaded_to":1137,"date":"2016-12-05 21:29:03","modified":"2016-12-05 21:29:03","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\/1137","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=1137"}],"version-history":[{"count":0,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/posts\/1137\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/media?parent=1137"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/categories?post=1137"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.newslab.sk\/en\/wp-json\/wp\/v2\/tags?post=1137"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}