{"id":1102,"date":"2016-12-09T14:42:50","date_gmt":"2016-12-09T13:42:50","guid":{"rendered":"http:\/\/www.newslab.sk\/2016\/12\/09\/paraneoplasticke-neurologicke-syndromy-a-in-vitro-diagnostika-onkoneuronalnych-protilatok\/"},"modified":"2017-10-03T13:29:18","modified_gmt":"2017-10-03T11:29:18","slug":"paraneoplastic-neurological-syndrome-and-in-vitro-diagnosis-of-onconeural-antibodies","status":"publish","type":"post","link":"https:\/\/www.newslab.sk\/en\/paraneoplastic-neurological-syndrome-and-in-vitro-diagnosis-of-onconeural-antibodies\/","title":{"rendered":"Paraneoplastic neurological syndrome and in vitro diagnosis of onconeural antibodies"},"content":{"rendered":"
*All tables, charts, graphs and pictures that are featured in this article can be found in the .pdf \r\nattachment at the end of the paper. <\/span>\r\n<\/strong><\/pre>\n
 <\/p>\n
\u00da<\/strong>vod<\/strong><\/p>\n
Paraneoplastick\u00e9 neurologick\u00e9 syndr\u00f3my (PNS) s\u00fa syndr\u00f3my vyvolan\u00e9 nepriamym p\u00f4soben\u00edm mal\u00edgneho ochorenia. Vyskytuj\u00fa sa asi u 1 % pacientov s n\u00e1dormi, vy\u0161\u0161\u00ed v\u00fdskyt je pozorovan\u00fd pri malobunkovom karcin\u00f3me p\u013e\u00fac (viac ako 5 %), pri lymf\u00f3moch a myel\u00f3moch (10 %). Postihuj\u00fa r\u00f4zne \u010dasti nervov\u00e9ho syst\u00e9mu od centr\u00e1lneho nervov\u00e9ho syst\u00e9mu pri limbickej encefalit\u00edde a\u017e po nervovosvalov\u00fa platni\u010dku pri myast\u00e9nii gravis.<\/p>\n
Objav protil\u00e1tok proti neuron\u00e1lnym antig\u00e9nom exprimovan\u00fdm v n\u00e1dore, teda onkoneuron\u00e1lnych protil\u00e1tok, viedol \u00a0k potvrdeniu \u00a0hypot\u00e9zy o autoimunitnej patogen\u00e9ze niektor\u00fdch paraneoplastick\u00fdch jednotiek (1). Tieto autoprotil\u00e1tky sa via\u017eu na antig\u00e9ny lokalizovan\u00e9 v nervovom tkanive, \u010do je pravdepodobnou \u00a0pr\u00ed\u010dinou vzniku neurologick\u00fdch por\u00fach (2). Pod\u013ea Grausa m\u00f4\u017eeme paraneoplastick\u00e9 neurologick\u00e9 \u00a0syndr\u00f3my rozdeli\u0165 na klasick\u00e9 a neklasick\u00e9 (tabu\u013eka 1).<\/p>\n
 <\/p>\n
L<\/strong>a<\/strong>b<\/strong>o<\/strong>ra<\/strong>t\u00f3<\/strong>r<\/strong>n<\/strong>a diagnostika paraneoplastick\u00e9ho syndr\u00f3mu<\/strong><\/p>\n
Diagnostick\u00e9 \u00a0krit\u00e9ri\u00e1 PNS, ktor\u00e9 zaviedla neurologick\u00e1 spolo\u010dnos\u0165 Euronetwork, definuj\u00fa definit\u00edvnu a mo\u017en\u00fa diagn\u00f3zu paraneoplastick\u00e9ho syndr\u00f3mu \u00a0(obr\u00e1zok 1). V ich odl\u00ed\u0161en\u00ed zohr\u00e1va v\u00fdznamn\u00fa \u00a0\u00falohu i<\/em>n vitro <\/em>diagnostika onkoneuron\u00e1lnych \u00a0protil\u00e1tok v s\u00e9re alebo mozgovomiechovom moku pacienta.<\/p>\n
 <\/p>\n
I<\/em><\/strong>n vitro <\/em><\/strong>te<\/strong>s<\/strong>t<\/strong>y<\/strong><\/p>\n
S\u00e9rologick\u00e1 diagnostika neurologick\u00fdch ochoren\u00ed s pou\u017eit\u00edm vysoko\u0161pecifick\u00fdch a citliv\u00fdch testov na detekciu onkoneuron\u00e1lnych protil\u00e1tok (tabu\u013eka 2) vo ve\u013ekej miere \u00a0prispieva k stanoveniu \u00a0diagn\u00f3zy. Spektrum dobre definovan\u00fdch onkoneuron\u00e1lnych \u00a0protil\u00e1tok proti intracelul\u00e1rnym antig\u00e9nom zah\u0155\u0148a:<\/p>\n
\u2013\u00a0\u00a0 \u00a0protil\u00e1tky proti Hu, Yo, Ri, amfifyz\u00ednu, CV2, PNMA1, PNMA2, recover\u00ednu, tit\u00ednu, SOX 1 v izotype IgG.<\/p>\n
 <\/p>\n
I<\/strong>n<\/strong>t<\/strong>e<\/strong>r<\/strong>p<\/strong>r<\/strong>et<\/strong>\u00e1<\/strong>c<\/strong>i<\/strong>a v\u00fdsledkov onkoneuron\u00e1lnych protil\u00e1tok vo vz\u0165ahu k rozl\u00ed\u0161eniu PNS<\/strong><\/p>\n
Klasick\u00e9 PNS, ak s\u00fa diagnostikovan\u00e9, vy\u017eaduj\u00fa intenz\u00edvne p\u00e1tranie po okultnom n\u00e1dore, a to aj v pr\u00edpade, \u017ee nie s\u00fa paralelne pr\u00edtomn\u00e9 onkoneuron\u00e1lne \u00a0protil\u00e1tky. Pri t\u00fdchto klasick\u00fdch PNS sa karcin\u00f3m m\u00f4\u017ee vyvin\u00fa\u0165 do 5 rokov od diagn\u00f3zy \u00a0neurologickej \u00a0poruchy \u00a0(4). Neklasick\u00e9 \u00a0PNS s\u00fa asociovan\u00e9 s n\u00e1dorom iba v niektor\u00fdch pr\u00edpadoch. Pri lie\u010dbe karcin\u00f3mov zaznamen\u00e1vame signifikantn\u00e9 zlep\u0161enie alebo vymiznutie PNS. V pr\u00edpade neklasick\u00fdch syndr\u00f3mov s pr\u00edtomnos\u0165ou onkoneuron\u00e1lnych protil\u00e1tok sa karcin\u00f3m m\u00f4\u017ee rozvin\u00fa\u0165 do 5 rokov.<\/p>\n
Medzi definit\u00edvne PNS patria klasick\u00e9 a neklasick\u00e9 neurologick\u00e9 syndr\u00f3my, ktor\u00fdch charakteristika je op\u00edsan\u00e1 vy\u0161\u0161ie.<\/p>\n
Mo\u017en\u00e9 PNS predstavuj\u00fa skupinu klasick\u00fdch neurologick\u00fdch syndr\u00f3mov, ale bez pr\u00edtomnosti onkoneuron\u00e1lnych\u00a0 protil\u00e1tok a karcin\u00f3mu. Patria sem aj neklasick\u00e9 neurologick\u00e9 syndr\u00f3my s negat\u00edvnymi onkoneuron\u00e1lnymi protil\u00e1tkami, pri\u010dom karcin\u00f3m sa m\u00f4\u017ee vyvin\u00fa\u0165 do dvoch rokov.<\/p>\n
Je nutn\u00e9 doda\u0165, \u017ee tieto autoprotil\u00e1tky niekedy nekoreluj\u00fa ani s aktivitou, ani so z\u00e1va\u017enos\u0165ou konkr\u00e9tneho syndr\u00f3mu. Diagnostick\u00e9 krit\u00e9ri\u00e1 neurologick\u00fdch PNS preto nie s\u00fa jednozna\u010dn\u00e9 a pozitivita onkoneur\u00e1lnych protil\u00e1tok m\u00f4\u017ee, ale nemus\u00ed by\u0165 pre diagn\u00f3zu vy\u017eadovan\u00e1 (5).<\/p>\n
Pod\u013ea Nemeckej neurologickej spolo\u010dnosti je nutn\u00e9 autoprotil\u00e1tky pri PNS v\u017edy stanovova\u0165 najmenej dvomi met\u00f3dami (6). Okrem nepriamej imunofluorescencie je nutn\u00e9 na konfirm\u00e1ciu pou\u017ei\u0165 imunoblotov\u00e9
\nstanovenie.<\/p>\n
 <\/p>\n
Predanalytick\u00e9 inform\u00e1cie<\/strong>
\nOdber:<\/em>
\nS\u00e9rum \u2013 uzatvoren\u00fd odberov\u00fd syst\u00e9m s g\u00e9lom
\nMozgovomiechov\u00fd mok<\/p>\n
 <\/p>\n
Autoprotil\u00e1tky pri neuromyelitis optica<\/strong>
\nKlinick\u00fd v\u00fdznam<\/em>
\nNeuromyelitis optica (NMO) postihuje optick\u00e9 nervy a miechu a m\u00e1 relapsremituj\u00faci priebeh. Patogeneticky ide o ak\u00fatny z\u00e1palov\u00fd proces namieren\u00fd proti astrocytom, ktor\u00fd sp\u00f4sobuje demyeliniz\u00e1ciu a axon\u00e1lne po\u0161kodenie zrakov\u00e9ho nervu (7, 8). V diferenci\u00e1lnej diagnostike je potrebn\u00e9 odl\u00ed\u0161i\u0165 ho od klasickej roztr\u00fasenej skler\u00f3zy, preto\u017ee lie\u010dba je rozdielna. Vysoko\u0161pecifick\u00fdm markerom NMO je pr\u00edtomnos\u0165 protil\u00e1tok proti akvapor\u00ednu 4 v s\u00e9re.
\nAkvapor\u00edn 4 je prote\u00edn, ktor\u00fd vytv\u00e1ra vodn\u00fd kan\u00e1l v centr\u00e1lnom nervovom syst\u00e9me, reguluje vodn\u00fa rovnov\u00e1hu medzi mozgom, cerebrospin\u00e1lnou tekutinou a krvou (9).
\nTieto vodn\u00e9 kan\u00e1ly s\u00fa pr\u00edtomn\u00e9 v miestach centr\u00e1lneho nervov\u00e9ho syst\u00e9mu, ktor\u00e9 s\u00fa atakovan\u00e9 pri neuromyelitis optica, teda hlavne zrakov\u00e9 nervy a miecha \u00a0(2, 8).<\/p>\n
 <\/p>\n
I<\/strong>n<\/strong>dik<\/strong>\u00e1<\/strong>c<\/strong>ie<\/strong><\/p>\n
    \n
  • Neuromyelitis optica<\/li>\n
  • Longitudin\u00e1lna extenz\u00edvna transverzn\u00e1 myelit\u00edda<\/li>\n
  • Optick\u00e1 neurit\u00edda<\/li>\n
  • Diferenci\u00e1lna diagnostika sklerosis multiplex<\/li>\n
  • SLE a prom\u00e1rny Sj\u00f6grenov syndr\u00f3m s neurologickou asoci\u00e1ciou.<\/li>\n<\/ul>\n
     <\/p>\n
    P<\/strong>r<\/strong>e<\/strong>d<\/strong>an<\/strong>a<\/strong>l<\/strong>y<\/strong>t<\/strong>i<\/strong>c<\/strong>k<\/strong>\u00e9 inform\u00e1cie<\/strong><\/p>\n
    Odber:
    \n<\/em>S\u00e9rum \u2013 uzatvoren\u00fd odberov\u00fd syst\u00e9m s g\u00e9lom
    \nMozgovomiechov\u00fd mok<\/p>\n
     <\/p>\n
    A<\/strong>u<\/strong>to<\/strong>pr<\/strong>o<\/strong>t<\/strong>il<\/strong>\u00e1<\/strong>t<\/strong>k<\/strong>y pri autoimunitnej encefalit\u00edde<\/strong><\/p>\n
    Kli<\/strong>ni<\/strong>c<\/strong>k<\/strong>\u00fd v\u00fdznam<\/strong><\/p>\n
    Limbick\u00e1 encefalit\u00edda je z\u00e1palov\u00e9 ochorenie mozgu s ak\u00fatnym a\u017e subak\u00fatnym rozvojom. Je charakterizovan\u00e1 poruchou kr\u00e1tkodobej pam\u00e4ti, v\u00fdskytom parci\u00e1lnych alebo generalizovan\u00fdch epileptick\u00fdch z\u00e1chvatov, zmenou osobnosti, \u00fazkos\u0165ou alebo depresiou, \u010duchov \u00fd- mi alebo chu\u0165ov\u00fdmi halucin\u00e1ciami, poruchami sp\u00e1nku a poruchou homeostatick\u00fdch funkci\u00ed (5). Tieto sympt\u00f3my m\u00f4\u017eu ma\u0165 non-para-neoplastick\u00fa alebo paraneoplastick\u00fa etiol\u00f3giu asociovan\u00fa s Hu, Ma2\/ Ta, CRM5\/C V2 protil\u00e1tkami (tabu\u013eka 3). Autoimunitn\u00e1 encefalit\u00edda je asociovan\u00e1 s protil\u00e1tkami proti membr\u00e1nov\u00fdm a synaptick\u00fdm antig\u00e9nom (tabu\u013eka 3). Pri pozit\u00edvnom laborat\u00f3rnom n\u00e1leze je nutn\u00e9 p\u00e1tra\u0165 po pr\u00edtomnosti n\u00e1dorov.<\/p>\n
     <\/p>\n
    I<\/strong>n<\/strong>dik<\/strong>\u00e1<\/strong>c<\/strong>ie<\/strong><\/p>\n
    Limbick\u00e1 encefalit\u00edda Morvanov syndr\u00f3m Paraneoplastick\u00e1 etiol\u00f3gia
    \nOnkologick\u00e1 asoci\u00e1cia pr\u00edtomnosti autoprotil\u00e1tok<\/p>\n
     <\/p>\n
    P<\/strong>r<\/strong>e<\/strong>d<\/strong>an<\/strong>a<\/strong>l<\/strong>y<\/strong>t<\/strong>i<\/strong>c<\/strong>k<\/strong>\u00e9 inform\u00e1cie<\/strong><\/p>\n
    Odber:
    \n<\/em>S\u00e9rum \u2013 uzatvoren\u00fd odberov\u00fd syst\u00e9m s g\u00e9lom
    \nMozgovomiechov\u00fd mok<\/p>\n
     <\/p>\n
    Dos<\/strong>t<\/strong>up<\/strong>nos<\/strong>\u0165 vy\u0161etrenia <\/strong><\/p>\n
    Centr\u00e1lne laborat\u00f3rium Ko\u0161ice Centr\u00e1lne laborat\u00f3rium Bratislava<\/p>\n
     <\/p>\n
    Z<\/strong>\u00e1<\/strong>ver<\/strong><\/p>\n
      \n
    1. Asi dve tretiny \u00a0PNS predch\u00e1dzaj\u00fa \u00a0diagn\u00f3zu vlastn\u00e9ho \u00a0n\u00e1doru.
      \nPr\u00edtomnos\u0165 onkoneuron\u00e1lnych \u00a0protil\u00e1tok v s\u00e9re pacientov preto m\u00f4\u017ee v\u010das odhali\u0165 pr\u00edtomnos\u0165 n\u00e1doru a odpor\u00fa\u010da sa ako cielen\u00fd onkologick\u00fd skr\u00edningov\u00fd test. Ich pr\u00edtomnos\u0165 \u00a0m\u00f4\u017ee by\u0165 prv\u00fdm varovn\u00fdm sign\u00e1lom, ktor\u00fd sa objavuje aj nieko\u013eko mesiacov \u00a0sk\u00f4r ako prim\u00e1rny n\u00e1dor.<\/li>\n<\/ol>\n
        \n
      1. Ak s\u00fa pr\u00edtomn\u00e9 \u00a0onkoneuron\u00e1lne \u00a0protil\u00e1tky v s\u00e9re alebo v likvore, je nutn\u00e9 p\u00e1tra\u0165 po n\u00e1dore.<\/li>\n
      2. Pr\u00edtomnos\u0165, \u00a0respekt\u00edve nepr\u00edtomnos\u0165 \u00a0autoprotil\u00e1tok je potrebn\u00e9 laborat\u00f3rne potvrdi\u0165 inou met\u00f3dou.<\/li>\n<\/ol>\n
         <\/p>\n
        L<\/strong>it<\/strong>e<\/strong>ra<\/strong>t<\/strong>\u00fa<\/strong>ra<\/strong><\/p>\n
          \n
        1. Maverakis E, Goodrazi H, Wehrli LN, Ono Y, Garcia MS. The etiology of paraneoplastic au- toimmunity. Clinic Rev Allerg Immunol. <\/em>2012;42:135\u201314<\/li>\n
        2. \u0160toura\u010d P, Ambler Z. Paraneoplastick\u00e9 neurologick\u00e9 syndromy \u2013 z\u00e1kladn\u00ed charakteristika, klasifikace, etiopatogeneze a diagnostika. N<\/em>eu<\/em>r<\/em>ol<\/em>o<\/em>gi<\/em>e pro praxi. <\/em>2013;14(1):8\u201315.<\/li>\n<\/ol>\n
            \n
          1. Graus F, Delattre JY, Antoine \u00a0JC, Dalmau \u00a0J, Giometto \u00a0B, Grisold \u00a0W, Honnorat \u00a0J, Smitt \u00a0PS, Vedeler Ch, Verschuueren JJGM, Vincent \u00a0A, Voltz R. Reccommended \u00a0diagnostic criteria for paraneoplastic neurological syndromes. J Neurol Neurosurg Psychiatry. <\/em>2004;75:1135 \u20131140.<\/li>\n
          2. Roberts WK, Darnell RB. Neuroimmunology of the paraneoplastic neurological degenerations. C<\/em>ur<\/em>r Opin Immunol. <\/em>2004;16:616\u2013622.<\/li>\n<\/ol>\n
              \n
            1. Weinshenker BG, Wingerchuk DM. Neuromyelitis optica: clinical syndrome and the NMO\u2013 IgG autoantibody marker. C<\/em>ur<\/em>r Top Microbiol <\/em>I<\/em>mm<\/em>u<\/em>no<\/em>l<\/em>. 2008;318:343\u2013356.<\/li>\n<\/ol>\n
                \n
              1. Takahashi T, Fujihara K, Nakashima I, Misu T, Miyazawa I, Nakamura \u00a0M, Watanabe \u00a0S, IshiiN, Itoyama \u00a0Y. Establishment of a new sensitive assay for anti-human \u00a0aquaporin-4 \u00a0antibody in neuromyelitis optica. J Exp Med. <\/em>2006;210:1365\u20131377.<\/li>\n
              2. Jarius S, Wildemann B. Neuromyelitis optica. D<\/em>e<\/em>r Nervenarz <\/em>2007;12:1365\u20131377.<\/li>\n
              3. Voltz R. Marker paraneoplasticher neurologischer Erkrankungen. J Lab Med. <\/em>2004;28:431\u2013438.<\/li>\n
              4. Waters P, Vincent A. Detection of Anti-Aquaporin -4 Antibodies in Neuromyelitis Optica. Current Status of the Assays. T<\/em>h<\/em>e International <\/em>M<\/em>S Journal. <\/em>2008;15:99\u2013105.<\/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 Paraneoplastick\u00e9 neurologick\u00e9 syndr\u00f3my (PNS) s\u00fa syndr\u00f3my vyvolan\u00e9 nepriamym p\u00f4soben\u00edm mal\u00edgneho ochorenia. Vyskytuj\u00fa sa asi u 1 % pacientov s n\u00e1dormi, vy\u0161\u0161\u00ed v\u00fdskyt je pozorovan\u00fd pri malobunkovom karcin\u00f3me p\u013e\u00fac<\/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":[712,711],"class_list":["post-1102","post","type-post","status-publish","format-standard","hentry","category-imunology","tag-onconeural-antibodies","tag-paraneoplastic-syndrome","typ_clanku-review-article"],"acf":{"abstrakt":"
                Paraneoplastic syndrome is a collection of all the symptoms that occur due to presence of a tumor, but that are not directly related to its growth nor the development of metastases. It may affect any part of the nervous system, neuromuscular junction and muscle, or individual cells, for example ganglion cells of the posterior brain stems. The syndrome arises due to a crossed immune response between tumor cells and components of the nervous system. The presence of paraneoplastic syndrome may be the first warning sign that appears even several months earlier than the primary tumor.<\/p>\n
                Key words<\/strong>: paraneoplastic syndrome, onconeural antibodies<\/p>\n","casopis":[{"ID":995,"post_author":"7","post_date":"2016-11-16 12:14:30","post_date_gmt":"2016-11-16 11:14:30","post_content":"
                Biochemistry <\/strong><\/h4>\r\n
                  \r\n \t
                • Biochemical inflammation markers<\/li>\r\n \t
                • Biochemical examinations in liver diseases<\/li>\r\n \t
                • Biochemical diagnosis in diseases of GIT<\/li>\r\n \t
                • Hypoglycemia<\/li>\r\n \t
                • Urolithiasis as a result of metabolic diseases<\/li>\r\n \t
                • Indication and application of tumor markers in clinical practice<\/li>\r\n \t
                • Monoclonal gammopathies \u2013 laboratory examinations in diagnosis and monitoring<\/li>\r\n \t
                • Hormones in diagnosis of reproductive function disorders<\/li>\r\n \t
                • Cerebrospinal fluid diagnosis of diseases affecting the nervous system<\/li>\r\n \t
                • Determining trace elements in blood serum<\/li>\r\n<\/ul>\r\n
                  Genetics<\/strong><\/h4>\r\n
                    \r\n \t
                  • Assessing the therapeutic response in patients with chronic myelocyte leukemia treated with tyrosine kinase inhibitors<\/li>\r\n \t
                  • Hormones in diagnosis of reproductive functions\u2019 disorders<\/li>\r\n<\/ul>\r\n
                    Hematology <\/strong><\/h4>\r\n
                      \r\n \t
                    • Anemias \u2013 laboratory diagnosis of the most frequently prevalent types of anemia<\/li>\r\n \t
                    • Laboratory and hematological technical equipment<\/li>\r\n<\/ul>\r\n
                      Immunology <\/strong><\/h4>\r\n
                        \r\n \t
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