{"id":1170,"date":"2017-01-31T21:29:25","date_gmt":"2017-01-31T20:29:25","guid":{"rendered":"http:\/\/www.newslab.sk\/2017\/01\/31\/nove-biomarkery-v-diagnostike-iga-nefropatie\/"},"modified":"2017-10-04T14:25:22","modified_gmt":"2017-10-04T12:25:22","slug":"new-biomarkers-in-diagnosis-of-iga-nephropathy","status":"publish","type":"post","link":"https:\/\/www.newslab.sk\/en\/new-biomarkers-in-diagnosis-of-iga-nephropathy\/","title":{"rendered":"New Biomarkers in Diagnosis of IgA Nephropathy"},"content":{"rendered":"
*All tables, charts, graphs and pictures that are featured in this article can be found in the .pdf\u00a0\r\nattachment at the end of the paper.\r\n\r\n<\/strong><\/span><\/pre>\n
\u00da<\/strong>vod<\/strong><\/p>\n
IgA \u00a0nefropatia \u00a0(IgAN), \u00a0po prv\u00fdkr\u00e1t op\u00edsan\u00e1 v roku 1968 ako Bergerova choroba, je celosvetovo naj\u010dastej\u0161ou prim\u00e1rnou glomerulonefrit\u00eddou. U 20 \u2013 40 % pacientov ochorenie v priebehu 20 rokov progreduje do chronick\u00e9ho zlyhania obli\u010diek. Na diagn\u00f3zu je potrebn\u00e1 ren\u00e1lna biopsia s imunof luorescen\u010dn\u00fdm vy\u0161etren\u00edm, \u00a0ktor\u00e9 potvrd\u00ed pr\u00edtomnos\u0165 depozitov komplexov IgA1 s IgG a zlo\u017ekami komplementu v mezangiu \u00a0glomerulov \u00a0(1). Viac ako 50 % pacientov \u00a0m\u00e1 zv\u00fd\u0161en\u00e9 s\u00e9rov\u00e9 koncentr\u00e1cie IgA a cirkuluj\u00facich imunokomplexov obsahuj\u00facich IgA. Ochorenie sa prejavuje intermitentnou \u00a0makroskopickou hemat\u00fariou a vo v\u00e4\u010d\u0161ine pr\u00edpadov miernou protein\u00fariou (do 1 g\/de\u0148), ktor\u00e9 sl\u00fa\u017eia aj ako indik\u00e1tory aktivity ochorenia a\u017e do stanovenia \u00a0diagn\u00f3zy (2). \u0160pecifick\u00e9 neinvaz\u00edvne biomarkery sa pre toto ochorenie rutinne nepou\u017e\u00edvaj\u00fa.<\/p>\n
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P<\/strong>a<\/strong>t<\/strong>og<\/strong>e<\/strong>n<\/strong>\u00e9<\/strong>z<\/strong>a<\/strong><\/p>\n
IgAN m\u00e1 zn\u00e1mky autoimunitn\u00e9ho ochorenia, v ktorom s\u00fa autoantig\u00e9n aj autoprotil\u00e1tka odvoden\u00e9 z rovnakej bunkovej l\u00ednie (CD19+ B-lymfocyty). V centre viacer\u00fdch patogenick\u00fdch \u00a0faktorov stoj\u00ed aberantn\u00e1 glykozyl\u00e1cia p\u00e1ntovej oblasti IgA1, ktor\u00e1 je sp\u00f4soben\u00e1 \u00a0v\u00e4\u010d\u0161inou genetick\u00fdmi \u00a0defektmi buniek produkuj\u00facich \u00a0IgA (3). V\u00fdsledkom \u00a0s\u00fa polym\u00e9rne molekuly IgA1 chudobn\u00e9 na galakt\u00f3zu, \u00a0ktor\u00e9 s\u00fa rozpozn\u00e1van\u00e9 prirodzen\u00fdmi autoprotil\u00e1tkami (oligoklonov\u00e9 \u00a0IgG a mo\u017eno \u00a0aj IgA1) a u disponovan\u00fdch jedincov\u00a0 ved\u00fa k tvorbe cirkuluj\u00facich imunokomplexov. Tieto sa ukladaj\u00fa v mezangiu glomerulov a ich unik\u00e1tne chemick\u00e9 zlo\u017eenie a trojrozmern\u00e1 \u0161trukt\u00fara sp\u00fa\u0161\u0165aj\u00fa kask\u00e1du z\u00e1palov\u00fdch medi\u00e1torov \u00fastiacu do po\u0161kodenia glomerulov (obr\u00e1zok 1) (4).<\/p>\n
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P<\/strong>o<\/strong>t<\/strong>e<\/strong>n<\/strong>c<\/strong>i\u00e1l<\/strong>n<\/strong>e nov\u00e9 diagnostick\u00e9 a prognostick\u00e9 markery<\/strong><\/p>\n
Zlat\u00fdm \u0161tandardom \u00a0diagnostiky aj pos\u00fadenia \u00a0aktivity ochorenia \u00a0je obli\u010dkov\u00e1 biopsia, ktor\u00fa v\u0161ak mnohokr\u00e1t \u00a0nemo\u017eno \u00a0vykona\u0165 pre rizik\u00e1 s \u0148ou spojen\u00e9 a tie\u017e z etick\u00fdch \u010di soci\u00e1lno-ekonomick\u00fdch d\u00f4vodov. H\u013eadaj\u00fa sa preto nov\u0161ie citliv\u00e9 a neivaz\u00edvne \u00a0markery, ktor\u00e9 by boli pr\u00ed- nosom pri terapeutick\u00fdch rozhodnutiach v ka\u017edom \u0161t\u00e1diu IgAN. V roku<\/p>\n
2007 Moldoveanu et al. vyvinuli s\u00e9rologick\u00fd \u00a0test na kvantifik\u00e1ciu galaktozyl-deficientnej formy IgA1 (Gd-IgA1), ktor\u00fd bol zalo\u017een\u00fd na \u0161pecifickej v\u00e4zbe slima\u010dieho lekt\u00ednu (H<\/em>elix aspersa<\/em>) \u00a0s acetyl-galaktozam\u00ednom v p\u00e1ntovej oblasti IgA1. Autori zistili, \u017ee s\u00e9rov\u00e9 hladiny Gd-IgA1 mali 77 % senzitivitu a 94 % \u0161pecificitu pri odl\u00ed\u0161en\u00ed pacientov \u00a0s IgAN a zdrav\u00fdch jedincov (5). Met\u00f3du s pou\u017eit\u00edm lekt\u00ednu vyu\u017e\u00edvali viacer\u00ed autori v z\u00e1kladnom aj \u00a0klinickom \u00a0v\u00fdskume. \u00a0Berthoux et al. \u00a0deklarovali, \u00a0\u017ee koncentr\u00e1cie Gd-IgA1 a imunokomplexov Gd-IgA1\/IgG m\u00f4\u017eu ma\u0165 predikt\u00edvnu hodnotu pri sledovan\u00ed progresie IgAN do \u0161t\u00e1dia obli\u010dkov\u00e9ho \u00a0zlyhania (6). In\u00ed autori sledovali s\u00e9rov\u00e9 koncentr\u00e1cie Gd-IgA1 a ich cirkuluj\u00facich imunokomplexov ako neinvaz\u00edvny marker na pos\u00fadenie \u00a0aktivity ochorenia \u00a0a na\u0161li ich dobr\u00fa korel\u00e1ciu s hemat\u00fariou a protein\u00fariou (7). V s\u00fa\u010dasnosti s\u00fa dostupn\u00e9 \u00a0ELISA testy vyu\u017e\u00edvaj\u00face monoklonov\u00e9 \u00a0protil\u00e1tky proti Gd-IgA1, ktor\u00e9 deklaruj\u00fa v\u00e4\u010d\u0161iu robustnos\u0165 a stabilitu v porovnan\u00ed s lekt\u00ednov\u00fdmi met\u00f3dami (8).<\/p>\n
In\u00fdm \u0161tudovan\u00fdm markerom je CD89, solubiln\u00fd receptor pre IgA (sCD89), exprimovan\u00fd na povrchu monocytov a makrof\u00e1gov, ktor\u00fd v cirkul\u00e1cii via\u017ee imunokomplexy \u00a0Gd-IgA1 \u2013 IgG alebo Gd-IgA1 \u2013 IgA. Tento trimolekulov\u00fd komplex sa po v\u00e4zbe s transfer\u00ednov\u00fdm receptorom \u00a0(TfR) uklad\u00e1 v mezangiu a prispieva k depozitom \u00a0a z\u00e1palov\u00e9mu po\u0161kodeniu glomerulov. Uvo\u013e\u0148ovanie sCD89 z povrchu cirkuluj\u00facich myeloidn\u00fdch buniek nast\u00e1va na za\u010diatku cel\u00e9ho patogenetick\u00e9ho procesu a mohlo by by\u0165 v\u010dasn\u00fdm indik\u00e1torom relapsu ochorenia po transplant\u00e1cii (9).<\/p>\n
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Z<\/strong>\u00e1<\/strong>ver<\/strong><\/p>\n
Patologick\u00e1 glykozyl\u00e1cia IgA s tvorbou degalaktozylovan\u00fdch polym\u00e9r- nych molek\u00fal IgA1 je jedn\u00fdm z k\u013e\u00fa\u010dov\u00fdch faktorov v patogen\u00e9ze vzniku a progresie IgAN. Na klinick\u00fa manifest\u00e1ciu nefrit\u00eddy s\u00fa v\u0161ak potrebn\u00e9 \u010fal\u0161ie autoimunitn\u00e9 procesy modulovan\u00e9 \u00a0genetick\u00fdmi aj environment\u00e1lnymi faktormi. Nov\u0161ie neinvaz\u00edvne biomarkery, ktor\u00e9 sa priebe\u017ene validuj\u00fa v klinick\u00fdch \u0161t\u00fadi\u00e1ch, predstavuj\u00fa s\u013eubn\u00fd neinvaz\u00edvny prostriedok na identifik\u00e1ciu rizikov\u00fdch jedincov, na diagnostiku ochorenia, sledovanie jeho aktivity a progresie v r\u00f4znych \u0161t\u00e1di\u00e1ch ochorenia.<\/p>\n
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L<\/strong>it<\/strong>e<\/strong>ra<\/strong>t<\/strong>\u00fa<\/strong>ra<\/strong><\/p>\n
1<\/strong>. <\/strong>Cattran DC, et al. The Oxford classification of IgA nephropathy: rationale, clinicopathological correlations, and classification. Working Group of the International IgA Nephropathy Network and the renal Pathology Society [online]. K<\/em>idn<\/em>e<\/em>y In <\/em>2009;76(5):534\u20135. Available from: <http:\/\/www.kidney-international.org\/article\/S0085-2538%2815%2954011-8\/pdf<\/a>>. Accessed April 21, 2015.<\/span><\/p>\n
2<\/strong>. <\/strong>Goto M, Wakai K, Kawamura T, et al. A scoring system to predict renal<\/span> outcome \u00a0in IgA nephropathy: \u00a0a nationwide \u00a010-year prospective \u00a0cohor t study. \u00a0Ne<\/em>ph<\/em>rol Dial Transplant.\u00a0<\/em>2009;24:3068\u201374.<\/p>\n
3<\/strong>. <\/strong>Suzuki H, Moldoveanu Z, Hall S, et al. IgA1-secreting cell lines from patients with IgA nephropathy produce aberrantly glycosylated IgA1. J Clin Inves <\/em>2008;118:629\u2013639.<\/p>\n
4<\/strong>. <\/strong>Novak J, Tomana M, Matousovic K, et al. IgA1-containing immune complexes in IgA nephropathy differentially affect proliferation of mesangial cells [online]. K<\/em>idney Int. <\/em>2005;67(2):504\u2013513. Available from: <http:\/\/www.kidney-international.org\/article\/S0085-2538%2815%2950485-<\/a><\/span>7\/pdf>. Accessed April 21, 2015.<\/span><\/p>\n
5<\/strong>. <\/strong>Moldoveanu Z, Wyatt RJ, Lee JY, et al. Patients with IgA nephropathy have increased serum galactose-deficient IgA1 levels [online]. K<\/em>id<\/em>ne<\/em>y <\/em>I<\/em> 2007;71:1148\u20131154. Available from:\u00a0<http:\/\/www.kidney-international.org\/article\/S0085-2538%2815%2952272-2\/pdf<\/a>>. Accessed\u00a0<\/span>April 21, 2015.<\/span><\/p>\n
6<\/strong>. <\/strong>Berthoux F, Suzuki H, Thibaudin L, et al. Autoantibodies targeting galactose-deficient IgA1 associate with progression of IgA nephropathy. J Am Soc Nephrol. <\/em>2012;23:1579\u201387.<\/p>\n
7<\/strong>. <\/strong>Suzuki Y, Matsuzaki K, Suzuki H, et al. Serum levels of galactose-deficient immunoglobulin (Ig) A1 and related immune complex are associated with disease activity of IgA nephro- pathy. Clin Exp Nephrol. <\/em>2014;18:770\u2013777.<\/p>\n
8<\/strong>. <\/strong>Yasutake J, Suzuki Y, Suzuki H, et al. Novel lectin-independent approach to detect galactose-deficient IgA1 in IgA nephropathy. Ne<\/em>ph<\/em>r<\/em>o<\/em>l Dial Transplant. <\/em>2015;30:1315\u20131321.<\/p>\n
9<\/strong>. <\/strong>Berthelot F, Robert T, Vuiblet V, et al. Recurrent IgA nephropathy \u00a0is predicted\u00a0 by altered glycosylated IgA, autoantibodies and soluble CD89 complexes [online]. K<\/em>idn<\/em>e<\/em>y In <\/em>2015;88:815\u20138 Available from: 2815%2932243-<<\/a>http:\/\/www.kidney-international.org\/article\/S2157-1716%<\/a><\/span>7\/pdf>. Accessed May 2, 2016.<\/p>\n","protected":false},"excerpt":{"rendered":"
*All tables, charts, graphs and pictures that are featured in this article can be found in the .pdf\u00a0 attachment at the end of the paper. \u00davod IgA \u00a0nefropatia \u00a0(IgAN), \u00a0po prv\u00fdkr\u00e1t op\u00edsan\u00e1 v roku 1968 ako Bergerova choroba, je celosvetovo naj\u010dastej\u0161ou prim\u00e1rnou glomerulonefrit\u00eddou. U 20 \u2013 40 % pacientov ochorenie v priebehu 20 rokov progreduje<\/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":[759,761,760,506],"class_list":["post-1170","post","type-post","status-publish","format-standard","hentry","category-biochemistry","tag-autoimmunity-disease","tag-diagnostic-marker","tag-galactosyl-deficient-iga1","tag-iga-nephropathy","typ_clanku-news"],"acf":{"abstrakt":"
IgA nephropathy is currently considered an autoimmunity disease with a specific autoantigen (galactosyl-deficient IgA1), specific autoantibodies (IgG a IgA1), production of immunocomplexes and their subsequent deposit in mesangium and inflammatory damage of glomeruli. Pathogenesis of the disease is influenced also by other factors, including genetics, external factors and interaction between multiple present risks. New knowledge is gradually applied in clinical practice, particularly in the shape of determining serum biomarkers in patients with IgA nephropathy.<\/p>\n
Key words: <\/strong>IgA nephropathy, autoimmunity disease, galactosyl-deficient IgA1, diagnostic marker<\/p>\n","casopis":[{"ID":991,"post_author":"7","post_date":"2017-02-01 09:43:42","post_date_gmt":"2017-02-01 08:43:42","post_content":"