{"id":9944,"date":"2020-04-23T04:51:59","date_gmt":"2020-04-23T01:51:59","guid":{"rendered":"https:\/\/www.synevo.ro\/product\/predispozitie-genetica-boala-celiaca-hla-dq2-dq8\/"},"modified":"2025-01-30T16:40:15","modified_gmt":"2025-01-30T14:40:15","slug":"predispozitie-genetica-boala-celiaca-hla-dq2-dq8","status":"publish","type":"product","link":"https:\/\/old.synevo.md\/ru\/shop\/predispozitie-genetica-boala-celiaca-hla-dq2-dq8\/","title":{"rendered":"\u0413\u0435\u043d\u0435\u0442\u0438\u0447\u0435\u0441\u043a\u0430\u044f \u043f\u0440\u0435\u0434\u0440\u0430\u0441\u043f\u043e\u043b\u043e\u0436\u0435\u043d\u043d\u043e\u0441\u0442\u044c \u043a \u0446\u0435\u043b\u0438\u0430\u043a\u0438\u0438 (HLA-DQ2\/DQ8)"},"content":{"rendered":"<p><span style=\"font-size: medium;\">Boala celiaca (numita si celiachie, intoleranta la gluten, enteropatie glutenica, sprue celiac sau sprue nontropical) este o afectiune inflamatorie digestiva cronica, cauzata de ingestia de gluten, ce impiedica absorbtia nutrientilor, vitaminelor si mineralelor de catre intestin. Se caracterizeaza printr-o sensibilitate mentinuta pe tot parcursul vietii la\u00a0 fractiunile solubile in alcool ale glutenului: gliadinul din grau si prolaminele din orz, secara si ovaz, sensibilitate intalnita la persoanele predispuse genetic. Dintre fractiunile glutenului, gliadinul reprezinta cel mai toxic component. Nu este vorba despre o alergie, ci de o boala autoimuna mediata de catre limfocitele T, in care transglutaminaza tisulara din intestinul subtire formeaza cu gliadinul alimentar autoantigenul propriu-zis. Deoarece numai anumite antigene HLA leaga gliadinul si-l prezinta sistemului imun, boala apare la purtatorii acestor antigene. Astfel se explica caracterul familial al acestei afectiuni, inregistrandu-se o prevalenta de 10% la rudele de gradul I ale persoanelor afectate \u00a0si o concordanta a bolii de pana la 70% la gemenii monozigoti.<\/span><\/p>\n<p><span style=\"font-size: medium;\">Boala celiaca este destul de frecvent intalnita in populatie, in Europa avand o prevalenta de 1:200-1:500. Femeile sunt de 2-3 ori mai afectate decat barbatii<sup>1<\/sup>.<\/span><\/p>\n<p><span style=\"font-size: medium;\">Ca si in cazul altor boli inflamatorii autoimune in patogenia bolii celiace sunt incriminati factori genetici (prezenta anumitor antigene HLA), incarcarea cu gluten a organismului, precum si alti factori insuficient caracterizati care favorizeaza aparitia manifestarilor la unele persoane cu predispozitie genetica<sup>2<\/sup>.<\/span><\/p>\n<p><span style=\"font-size: medium;\">Susceptibilitatea fata de boala celiaca este conferita de anumite alele HLA de clasa a 2-a din regiunea HLA-DQ. Astfel, cei mai multi pacienti (90-95%) prezinta heterodimerul <strong>HLA-DQ2<\/strong> codificat de alelele <strong><em>DQA1*05<\/em><\/strong> si <strong><em>DQB1*02 (denumit \u015fi <b>HLA DQ2.5<\/b>)<\/em><\/strong>, in timp ce ~5% prezinta heterodimerul <strong>HLA-DQ8<\/strong> codificat de alelele <strong><em>DQA1*03<\/em><\/strong> si <strong><em>DQB1*0302<\/em><\/strong>. Majoritatea pacientilor prezinta haplotipul <strong>DR3-DQ2 (<em>DRB1*0301-DQA1*0501-DQB1*0201)<\/em><\/strong> sau sunt heterozigoti pentru <strong>DR5-DQ7\/DR7-DQ2 <em>(DRB1*11\/12-DQA1*0505-DQB1*0301\/DRB1*07-DQA1*0201<\/em>-<em>DQB1*0202)<\/em><\/strong>. Aceasta inseamna ca molecula dimerica DQ2 alcatuita dintr-un lant \u03b1 si un lant \u03b2 poate fi codificata de alele <strong><em>DQA1*0501<\/em><\/strong> si <strong><em>DQB1*0201 <\/em><\/strong>situate pe acelasi cromozom (configuratie <em>cis<\/em> \u2013 fig. 1A) sau de catre alele <strong><em>DQA1*0505 <\/em><\/strong>si <strong><em>DQB1*0202 <\/em><\/strong>situate pe cromozomi diferiti (configuratie <em>trans<\/em> \u2013 fig. 1A). Pacientii negativi pentru DQA1*05 si DQB1*02 sunt adesea pozitivi pentru haplotipul <strong><em>DRB1*04-DQA1*03- DQB1*0302 <\/em><\/strong>(haplotip <strong>DR4-DQ8<\/strong>). Molecula DQ8 alcatuita de asemenea dintr-un lant \u03b1 si un lant \u03b2 este codificata de alele situate pe acelasi cromozom (configuratie <em>cis<\/em> \u2013 fig. 1C). Foarte rar pacientii poarta fie numai lantul \u03b1 (*0501 sau *0505), fie numai lantul \u03b2 (*0201 sau *0202) al heterodimerului DQ2 (jumatate din heterodimerul DQ2)<sup>2;3;4;5<\/sup>.<\/span><\/p>\n<p><span style=\"font-size: medium;\"><a title=\"\" href=\"\/wp-content\/uploads\/2009\/08\/boala-celiaca2.jpg\" rel=\"wpdevart_lightbox lightbox-gallery-JT92dqgX\" data-=\"\" data-rl_title=\"\" data-rl_caption=\"\"><img decoding=\"async\" class=\"alignnone size-full wp-image-8293\" src=\"\/wp-content\/uploads\/2009\/08\/boala-celiaca2.jpg\" alt=\"-\" width=\"680\" height=\"278\"><img decoding=\"async\" class=\"alignnone size-full wp-image-8293\" src=\"\/wp-content\/uploads\/2009\/08\/boala-celiaca2.jpg\" alt=\"-\" width=\"680\" height=\"278\"><\/a><\/span><\/p>\n<p><span style=\"font-size: small;\"><em>Fig.1 Formarea moleculelor DQ2 si DQ8 (Adaptare dupa Celiac Disease, Gene Reviews)<\/em><\/span><\/p>\n<p><span style=\"font-size: medium;\">Susceptibilitatea fata de boala legata de genotipul HLA-DQ2 este transmisa <em>autozomal-dominant<\/em> \u0438\u043b\u0438 <em>autozomal recesiv<\/em> in functie de genotipurile HLA predispozante ale parintilor (vezi fig. 2A). Susceptibilitatea fata de boala legata de genotipul HLA-DQ8 este transmisa <em>autozomal-dominant <\/em>(vezi fig. 2B).<\/span><\/p>\n<p><span style=\"font-size: medium;\"><a title=\"\" href=\"\/wp-content\/uploads\/2009\/08\/boala-celiaca.jpg\" rel=\"wpdevart_lightbox lightbox-gallery-JT92dqgX\" data-=\"\" data-rl_title=\"\" data-rl_caption=\"\"><img decoding=\"async\" class=\"alignnone size-full wp-image-8291\" src=\"\/wp-content\/uploads\/2009\/08\/boala-celiaca.jpg\" alt=\"-\" width=\"667\" height=\"488\"><img decoding=\"async\" class=\"alignnone size-full wp-image-8291\" src=\"\/wp-content\/uploads\/2009\/08\/boala-celiaca.jpg\" alt=\"-\" width=\"667\" height=\"488\"><\/a><\/span><\/p>\n<p><em><span style=\"font-size: small;\">Fig. 2 Modul de transmitere a susceptibilitatii legate de DQ2 (A) si DQ8 (B) in familiile in care unul din parinti prezinta haplotipul HLA predispozant respectiv, iar celalalt nu prezinta acest haplotip. Varianta HLA-DQB1*0302 este mostenita intotdeauna impreuna cu secventa HLA-DQA1*03 ca urmare a dezechilibrului de linkaj <\/span><span style=\"font-size: small;\">(Adaptare dupa Celiac Disease, Gene Reviews)<\/span><\/em><\/p>\n<p><span style=\"font-size: medium;\">Deoarece 30% din populatia generala prezinta una dintre alelele HLA asociate cu boala celiaca (care codifica heterodimerii DQ2 si\/sau DQ8) si numai 3% dintre cei care prezinta unul sau ambii heterodimeri dezvolta boala, identificarea acestor alele nu stabileste diagnosticul ci indica numai un risc crescut. Pe de alta parte insa, absenta oricarei alele HLA asociate cu boala celiaca exclude practic acest diagnsotic<sup>1<\/sup>.<\/span><\/p>\n<p><span style=\"font-size: medium;\">Diagnosticul de boala celiaca se confirma prin efectuarea biopsiei de mucoasa intestinala, la care se constata modificari caracteristice (leziuni ce variaza ca severitate, de la atrofie pana la disparitia vilozitatilor intestinale). <\/span><\/p>\n<p><span style=\"font-size: medium;\">Anumite boli, mai ales cele autoimune, apar la pacientii cu celiachie de 10 ori mai frecvent decat in populatia generala. La aparitia lor concomitenta, de multe ori celiachia este asimptomatica: dermatita herpetiforma Duhring, deficit selectiv de Ig A, ciroza biliara primitiva, sindrom Sj\u00f6gren, diabet zaharat de tip I, sindrom Down sau Turner, boala Crohn, colita ulceroasa, osteoporoza, tiroidita autoimuna<sup>3<\/sup>.<\/span><\/p>\n<p><span style=\"font-size: medium;\">Expunerea la gluten este obligatorie pentru ca boala celiaca sa se manifeste la persoanele cu susceptibilitate genetica. Acest fapt este dovedit prin absenta leziunilor si simptomelor la persoanele cu boala celiaca la care s-a instituit dieta fara gluten.<\/span><\/p>\n<p><span style=\"font-size: medium;\">Proteinele din structura glutenului se caracterizeaza printr-un continut crescut de prolina si glutamina care le confera o rezistenta relativa fata de degradarea enzimatica si le permite astfel sa se mentina la dimensiunea necesara pentru se lega de moleculele DQ2 sau DQ8 de pe suprafata macrofagelor si de a stimula celulele T CD4+. Intr-adevar au fost izolate din mucoasa pacientilor cu boala celiaca celule T ce reactioneaza cu peptidele glutenului in prezenta moleculelor DQ2 sau DQ8. Pe de alta parte celulele T izolate din mucoasa normala nu sunt reactive fata de gluten chiar la persoanele DQ2+.<\/span><\/p>\n<p><span style=\"font-size: medium;\">Exista argumente foarte convingatoare cu privire la rolul important al celulelor T CD4+ din lamina propria in patogenia bolii celiace (vezi fig.2). Deoarece celulele T sunt separate de peptidele de gluten prin stratul epitelial, peptidele trebuie sa traverseze mucoasa, iar mecanismul acestei translocatii este neclar. In lamina proprie transglutaminazele tisulare actioneaza asupra peptidelor glutenului pentru a le deamida, transformand glutaminele selectate in acid glutamic incarcat negativ. S-a demonstrat ca peptidele de gliadin deamidate au capacitatea de a se lega mai bine de \u201csantul\u201d moleculei HLA de tip DQ2 sau DQ8 care prezinta \u201cbuzunare\u201d incarcate pozitiv. De fapt, celulele T CD4+ din lamina propria a mucoasei afectate recunosc in principal peptide de gliadin deamidate. Desi exista o mare variabilitate a secventelor peptidice specifice care activeaza celulele T izolate de la persoane diferite, a fost identificat un \u201cmotiv\u201c peptidic care poate activa un numar mare de clone de celule T izolate din mucoasa celiaca. Acest \u201cmotiv\u201c\u00a0 poate fi relationat cu \u201csantul\u201d DQ2 de legare a antigenului, a carui structura cristalina este cunoscuta. S-a estimat ca numarul proteinelor din grau, orz, secara care prezinta \u201cmotive\u201c corecte de legare DQ2 sau DQ8 reprezinta doar o mica fractiune din totalul secventelor potential prezente in aceste cereale. Celulele T CD4+ gliadin-specifice din lamina proprie a pacientilor cu celiachie secreta interferon gamma (INF-\u03b3), ceea ce sugereaza ca acestea sunt polarizate catre un fenotip efector Th1. Aceste celule activeaza o varietate de citokine inflamatorii, metaloproteinazele tisulare care se presupune ca genereaza leziunile histopatologice locale. INF-\u03b3 creste permeabilitatea intestinala si faciliteaza translocatia unui numar si mai mare de peptide, intretinand astfel un cerc vicios. Evenimentul care declanseaza intreaga cascada nu este inca precizat, dar infectiile gastrointestinale cu virusuri enterice au fost de mult suspectate ca fiind un trigger crucial. Lamina proprie contine celule T reglatoare (Tregl) dar rolul acestora in boala celiaca este putin cunoscut<sup>2<\/sup>.<\/span><\/p>\n<p><span style=\"font-size: medium;\"><a title=\"\" href=\"\/wp-content\/uploads\/2009\/08\/boala-celiaca1.jpg\" rel=\"wpdevart_lightbox lightbox-gallery-JT92dqgX\" data-=\"\" data-rl_title=\"\" data-rl_caption=\"\"><img decoding=\"async\" class=\"alignnone size-full wp-image-8292\" src=\"\/wp-content\/uploads\/2009\/08\/boala-celiaca1.jpg\" alt=\"-\" width=\"491\" height=\"325\"><img decoding=\"async\" class=\"alignnone size-full wp-image-8292\" src=\"\/wp-content\/uploads\/2009\/08\/boala-celiaca1.jpg\" alt=\"-\" width=\"491\" height=\"325\"><\/a><\/span><\/p>\n<p><span style=\"font-size: small;\"><em>\u00a0Fig. 2 Patogenia bolii celiace<\/em><\/span><\/p>\n<p><span style=\"font-size: medium;\">Transglutaminaza tisulara (tTG) a fost identificata ca fiind autoantigenul major in boala celiaca. In conditii patologice transglutaminaza (tTG) eliberata extracelular poate forma complexe cu proteine (sau cu peptide rezultate din hidroliza lor) cu un continut crescut in glutamina, ca cele din grau. Aceste complexe reprezinta neonatigene ce pot stimula de asemenea productia de anticorpi specifici; din punct de vedere diagnostic, anticorpii anti-tTG au o sensibilitate si specificitate de peste 95% pentru boala celiaca<sup>3<\/sup>.<\/span><\/p>\n<p><span style=\"font-size: medium;\"><strong><em>Recomandari pentru determinarea alelelor HLA de predispozitie <\/em><\/strong><em>\u00a0<\/em><\/span><\/p>\n<p style=\"padding-left: 30px;\"><span style=\"font-size: medium;\">\u2022 pacienti simptomatici cu niveluri echivoce de anticorpi anti-tTG sau cu un rezultat neconcludent la biopsia de mucoasa intestinala;<\/span><\/p>\n<p style=\"padding-left: 30px;\"><span style=\"font-size: medium;\">\u2022 pacienti anterior simptomatici care au devenit asimptomatici dupa instituirea dietei fara gluten si care nu doresc sa efectueze testul de provocare cu gluten;<\/span><\/p>\n<p style=\"padding-left: 30px;\"><span style=\"font-size: medium;\">\u2022 pacienti simptomatici care nu raspund la dieta fara gluten;<\/span><\/p>\n<p style=\"padding-left: 30px;\"><span style=\"font-size: medium;\">\u2022 diagnosticul diferential la un pacient care prezinta simptome similare bolii celiace;<\/span><\/p>\n<p style=\"padding-left: 30px;\"><span style=\"font-size: medium;\">\u2022 rudele de gradul 1 si 2 ale pacientilor cu boala celiaca;<\/span><\/p>\n<p style=\"padding-left: 30px;\"><span style=\"font-size: medium;\">\u2022 evaluarea pacientilor din grupele de risc amintite mai sus.<\/span><\/p>\n<p><span style=\"font-size: medium;\">In concluzie, testul este util pentru \u00a0<span style=\"text-decoration: underline;\">excluderea \u00a0unei celiachii si identificarea pacientilor cu risc<\/span><sup><sup>1;2;4<\/sup><\/sup>.<\/span><\/p>\n<p><span style=\"font-size: medium;\">In 2012 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) a elaborat un nou ghid cu privire la diagnosticul bolii celiace la copii. Astfel, testul genetic este considerat investigatia de prima linie la persoanele cu risc crescut. De asemenea, la copiii cu suspiciune clinica mare si serologie net pozitiva testul HLA poate fi utilizat ca instrument diagnostic, inlocuind biopsia de mucoasa duodenala<sup>6<\/sup>.<\/span><\/p>\n<p><span style=\"font-size: medium;\"><strong><em>Specimen recoltat<\/em><\/strong> \u2013 sange venos<sup>1<\/sup>.<\/span><\/p>\n<p><span style=\"font-size: medium;\"><strong><em>Recipient de recoltare<\/em><\/strong>\u00a0\u2013 vacutainer ce contine EDTA ca anticoagulant<sup>1<\/sup>.<\/span><\/p>\n<p><span style=\"font-size: medium;\"><strong><em>Cantitate recoltata <\/em><\/strong>\u2013 cat permite vacuumul<sup>1<\/sup>.<\/span><\/p>\n<p><span style=\"font-size: medium;\"><strong><em>Cauze de respingere<\/em><\/strong> <strong><em>a probei <\/em><\/strong>\u2013 folosirea heparinei ca anticoagulant; probe coagulate sau hemolizate.<\/span><\/p>\n<p><span style=\"font-size: medium;\"><strong><em>Stabilitate proba<\/em><\/strong> - <em>7 zile<\/em> la 2-8\u00baC<sup>1<\/sup>.<\/span><\/p>\n<p><span style=\"font-size: medium;\"><strong><em>Metoda<\/em><\/strong> - <\/span><span style=\"font-size: medium;\"><span style=\"text-decoration: underline;\">tehnologie ADN microarray<\/span>; sunt determinate genotipurile <i>HLA-DQA1<\/i> si <i>HLA-DQB1 <\/i>pentru a detecta perechile specifice de variante alelice asociate cu boala celiaca: <\/span><\/p>\n<p style=\"padding-left: 30px;\"><span style=\"font-size: medium;\">1. <i>HLA-DQA1<\/i>*0501, <i>HLA-DQB1<\/i>*0201 (HLA DQ2.5 in configuratia cis)<\/span><\/p>\n<p style=\"padding-left: 30px;\"><span style=\"font-size: medium;\"><i>2. HLA-DQA1<\/i>*0505, <i>HLA-DQB1<\/i>*0202 (HLA DQ2.5 in configuratia trans)<\/span><\/p>\n<p style=\"padding-left: 30px;\"><span style=\"font-size: medium;\">3. HLA-DQA1*0301, <i>HLA-DQB1<\/i>*0302 (HLA DQ8)<sup>1<\/sup>.<\/span><\/p>\n<p><span style=\"font-size: medium;\"><strong><em>Interpretarea rezultatelor<\/em><\/strong><\/span><\/p>\n<p><span style=\"font-size: medium;\">Un rezultat negativ pentru alelele de predispozitie HLA DQ2 si DQ8\u00a0 exclude virtual diagnsticul de boala celiaca si indica un risc extrem de scazut (&lt;1%) de a dezvolta boala in cursul vietii, indiferent de dieta<sup>1;4<\/sup>.<\/span><\/p>\n<p><span style=\"font-size: medium;\">Identificarea unei perechi de alele HLA predispozante\u00a0la o persoana confera un risc cumulat de 3% de a dezvolta boala celiaca.<\/span><\/p>\n<p><span style=\"font-size: medium;\">O ruda de gradul I a unei persoane cu boala celiaca care poarta aceeasi alela predispozanta prezinta un risc de pana la 40% de a dezvolta boala.<\/span><\/p>\n<p><span style=\"font-size: medium;\">Persoanele care prezinta numai genotipul HLA DQ8 au un risc mult mai mic decat cele care prezinta doar genotipul HLA DQ2.<\/span><\/p>\n<p><span style=\"font-size: medium;\">Nu exista o diferenta in ceea ce priveste severitatea bolii intre pacientii care prezinta numai genotipul HLA DQ8 si cei care poarta doar genotipul HLA DQ2.<\/span><\/p>\n<p><span style=\"font-size: medium;\">Persoanele care prezinta ambele genotipuri HLA-DQ2 si HLA-DQ8 nu au un risc mai mare de boala in comparatie cu cele care prezinta doar genotipul HLA DQ2; pe de alta parte, aceste persoane au o probabilitate mai mare de a dezvolta boala fata de cele care prezinta doar genotipul HLA DQ8.<\/span><\/p>\n<p><span style=\"font-size: medium;\">Homozigotia fata de o alela <em>DQB1*02<\/em> la o persoana DQ2+ confera un risc de cinci ori mai mare pentru boala celiaca in comparatie cu restul persoanelor DQ2+. De asemenea homozigotia fata de o alela <em>DQB1*02 <\/em>este raportata mai frecvent la persoanele cu tablou clasic de boala celiaca decat la cele cu manifestari atipice, precum si in cazurile de sprue refractar sau de limfom cu celula T asociat enteropatiei (Enteropathy-associated T-cell lymphoma = EATL).<\/span><\/p>\n<p><span style=\"font-size: medium;\">Persoanele care prezinta numai jumatate din heterodimerul DQ2 \u2013 numai o varianta <em>HLA-DQA1<\/em> (*0501 sau *0505) SAU <em>HLA-DQB1<\/em> (*0201 or *0202), dar nu ambele \u2013 pot dezvolta boala celiaca insa riscul este foarte mic comparativ cu cei care prezinta heterodimerul complet.<\/span><\/p>\n<p><span style=\"font-size: medium;\">Conform unor studii mai recente se considera ca subtipul HLA DQ2.2 (codificat de alelele DQA1*02:01 si DQB1*02:02), cu toate ca nu este inclus in criteriile de diagnostic (conform ESPGHAN 2012), ar putea fi asociat cu o forma mai usoara de boala celiaca. Din acest motiv laboratorul va comunica prezenta subtipului HLA DQ2.2 si va mentiona ca, desi nu au fost depistate constelatiile HLA clasice, nu poate fi exclus riscul de aparitie in viitor a bolii celiace<sup>7<\/sup>.<\/span><\/p>\n<p><span style=\"font-size: medium;\">Persoanele cu rezultat pozitiv la testul genetic vor fi monitorizate serologic la un interval de 3-5 ani<sup>2<\/sup>. <\/span><\/p>\n<p><b><i><span style=\"color: #000000;\"><span style=\"font-size: medium;\">Limite si interferente<\/span><\/span><\/i><\/b><\/p>\n<p><span style=\"font-size: medium;\">Identificarea unei constelatii HLA predispozante nu dovedeste existenta bolii celiace<sup>4<\/sup>.<\/span><\/p>\n<p>\u0411\u0438\u0431\u043b\u0438\u043e\u0433\u0440\u0430\u0444\u0438\u044f<\/p>\n<p>1. Laborator Synevo. Referintele specifice tehnologiei de lucru utilizate 2010. Ref Type: Catalog.<\/p>\n<p>2. Snyder L. C, O Young D, Green HR Peter, Taylor A. K. Celiac Disease. Gene Reviews, 2008. www.ncbi.nlh.gov. Reference Type: Internet Communication.<\/p>\n<p>3. Elson C.O., Smith E.D. Immunologic Disease of the Gastrointestinal Tract. In Clinical Immunology. Principles and Practice, Mosby, Elsevier, Third Edition, 2008, 1106-1109.<\/p>\n<p>4. Mayo Clinic, Mayo Medical Laboratories. Reference Laboratory Services for Health Care Organizations. Celiac-Associated HLA-DQ Alpha 1 and DQ Beta 1 High-Resolution DNA Typing, Blood www.mayomedicallaboratories.com. 2010. Ref Type: Internet Communication.<\/p>\n<p>5. Megiorni F, Pizzuti A. HLA-DQA1 and HLA-DQB1 in Celiac disease predisposition: practical implications of the HLA molecular Typing. In Journal of Biomedical Science., 2012, 19:88.<\/p>\n<p>6. S. Husby, S. Koletzko, R. Korponay-Szabo, M.L. Mearin, A. Phillips, R. Shamir, R. Troncone, K. Giersiepen, D. Branski, C. Catassi, M. Lelgeman, M. Maki, C. Ribes-Koninckx, A. Ventura, and K.P. Zimmer, for the ESPGHAN Working Group on Coeliac Disease Diagnosis, on behalf of the ESPGHAN Gastroenterology Committee. European Society for Pediatric Gastroenterology, Hepatology, and Nutrition Guidelines for the Diagnosis of Coeliac Disease. In JPGN Vol. 54, No.1, Jan. 2012.<\/p>\n<p>7. Mubarak A, Spierings E, Wolters V, van Hoogstraten I, Kneepkens CM, Houven R. Human leukocyte antigen DQ2.2 and celiac disease. In J Pediatr Gastroenterol Nutr 2013 Apr; 56(4):428-30.<\/p>","protected":false},"excerpt":{"rendered":"<p>\u0426\u0435\u043b\u0438\u0430\u043a\u0438\u044f (\u0433\u043b\u044e\u0442\u0435\u043d\u043e\u0432\u0430\u044f \u044d\u043d\u0442\u0435\u0440\u043e\u043f\u0430\u0442\u0438\u044f) \u2013 \u0445\u0440\u043e\u043d\u0438\u0447\u0435\u0441\u043a\u043e\u0435 \u0430\u0443\u0442\u043e\u0438\u043c\u043c\u0443\u043d\u043d\u043e\u0435 \u0437\u0430\u0431\u043e\u043b\u0435\u0432\u0430\u043d\u0438\u0435, \u043f\u043e\u0440\u0430\u0436\u0430\u044e\u0449\u0435\u0435 \u043f\u0438\u0449\u0435\u0432\u0430\u0440\u0438\u0442\u0435\u043b\u044c\u043d\u044b\u0439 \u0442\u0440\u0430\u043a\u0442 \u0433\u0435\u043d\u0435\u0442\u0438\u0447\u0435\u0441\u043a\u0438 \u043f\u0440\u0435\u0434\u0440\u0430\u0441\u043f\u043e\u043b\u043e\u0436\u0435\u043d\u043d\u044b\u0445 (HLA \u2013 DQ2, HLA \u2013 DQ8) \u043b\u0438\u0446, \u0438\u043c\u0435\u044e\u0449\u0438\u0445 \u043d\u0435\u043f\u0435\u0440\u0435\u043d\u043e\u0441\u0438\u043c\u043e\u0441\u0442\u044c \u043e\u0441\u043d\u043e\u0432\u043d\u043e\u0433\u043e \u0431\u0435\u043b\u043a\u0430 \u0437\u043b\u0430\u043a\u043e\u0432 (\u0433\u043b\u044e\u0442\u0435\u043d\u0430). \u0426\u0435\u043b\u0438\u0430\u043a\u0438\u044f \u0432\u044b\u0437\u044b\u0432\u0430\u0435\u0442 \u0445\u0440\u043e\u043d\u0438\u0447\u0435\u0441\u043a\u043e\u0435 \u0432\u043e\u0441\u043f\u0430\u043b\u0435\u043d\u0438\u0435 \u0441\u043b\u0438\u0437\u0438\u0441\u0442\u043e\u0439 \u043e\u0431\u043e\u043b\u043e\u0447\u043a\u0438 (\u0421\u041e) \u0442\u043e\u043d\u043a\u043e\u0439 \u043a\u0438\u0448\u043a\u0438, \u0432\u0435\u0434\u0443\u0449\u0435\u0435 \u043a \u0435\u0435 \u0430\u0442\u0440\u043e\u0444\u0438\u0438, \u043c\u0430\u043b\u044c\u0430\u0431\u0441\u043e\u0440\u0431\u0446\u0438\u0438, \u043f\u0440\u0438 \u044d\u0442\u043e\u043c \u0438\u043c\u0435\u0435\u0442\u0441\u044f \u0432\u043e\u0437\u043c\u043e\u0436\u043d\u043e\u0441\u0442\u044c \u043f\u043e\u043b\u043d\u043e\u0433\u043e \u0432\u043e\u0441\u0441\u0442\u0430\u043d\u043e\u0432\u043b\u0435\u043d\u0438\u044f \u0444\u0443\u043d\u043a\u0446\u0438\u0438 \u043e\u0440\u0433\u0430\u043d\u0430 \u0432 \u043e\u0442\u0432\u0435\u0442 \u043d\u0430 \u043f\u0440\u0435\u043a\u0440\u0430\u0449\u0435\u043d\u0438\u0435 \u043a\u043e\u043d\u0442\u0430\u043a\u0442\u0430 \u0441 \u0433\u043b\u044e\u0442\u0435\u043d\u043e\u043c (\u0431\u0435\u0437\u0433\u043b\u044e\u0442\u0435\u043d\u043e\u0432\u0443\u044e \u0434\u0438\u0435\u0442\u0443).<\/p>\n<p>HLA \u0440\u0430\u0441\u0448\u0438\u0444\u0440\u043e\u0432\u044b\u0432\u0430\u0435\u0442\u0441\u044f \u043a\u0430\u043a &#8220;\u0447\u0435\u043b\u043e\u0432\u0435\u0447\u0435\u0441\u043a\u0438\u0439 \u043b\u0435\u0439\u043a\u043e\u0446\u0438\u0442\u0430\u0440\u043d\u044b\u0439 \u0430\u043d\u0442\u0438\u0433\u0435\u043d&#8221;, \u043a\u043e\u0442\u043e\u0440\u044b\u0439 \u044f\u0432\u043b\u044f\u0435\u0442\u0441\u044f \u043e\u043f\u0440\u0435\u0434\u0435\u043b\u0435\u043d\u043d\u044b\u043c\u0438 \u043c\u043e\u043b\u0435\u043a\u0443\u043b\u0430\u043c\u0438, \u043d\u0430\u0445\u043e\u0434\u044f\u0449\u0438\u043c\u0438\u0441\u044f \u043d\u0430 \u043f\u043e\u0432\u0435\u0440\u0445\u043d\u043e\u0441\u0442\u0438 \u043a\u043b\u0435\u0442\u043e\u043a. \u0422\u0430\u043a\u0438\u0445 \u043c\u043e\u043b\u0435\u043a\u0443\u043b \u043c\u043e\u0436\u0435\u0442 \u0431\u044b\u0442\u044c \u0434\u043e 100 000 \u043d\u0430 \u043f\u043e\u0432\u0435\u0440\u0445\u043d\u043e\u0441\u0442\u0438 \u043e\u0434\u043d\u043e\u0439 \u043a\u043b\u0435\u0442\u043a\u0438, \u043d\u043e \u0441 \u0440\u0430\u0437\u0432\u0438\u0442\u0438\u0435\u043c \u0446\u0435\u043b\u0438\u0430\u043a\u0438\u0438 \u0441\u0432\u044f\u0437\u0430\u043d\u043e \u0434\u0432\u0435: HLA \u2013 DQ2, HLA \u2013 DQ8.<\/p>\n<p>\u041d\u0435\u043f\u0435\u0440\u0435\u043d\u043e\u0441\u0438\u043c\u043e\u0441\u0442\u044c \u0433\u043b\u044e\u0442\u0435\u043d\u0430 \u0441\u0432\u044f\u0437\u0430\u043d\u0430 \u0441 HLA-\u0433\u0430\u043f\u043b\u043e\u0442\u0438\u043f\u0430\u043c\u0438, \u0438 \u0440\u0438\u0441\u043a \u0440\u0430\u0437\u0432\u0438\u0442\u0438\u044f \u0446\u0435\u043b\u0438\u0430\u043a\u0438\u0438 \u043e\u0431\u0443\u0441\u043b\u043e\u0432\u043b\u0435\u043d \u043f\u043e \u043a\u0440\u0430\u0439\u043d\u0435\u0439 \u043c\u0435\u0440\u0435 \u0434\u0432\u0443\u043c\u044f \u0433\u0435\u043d\u0435\u0442\u0438\u0447\u0435\u0441\u043a\u0438\u043c\u0438 \u043b\u043e\u043a\u0443\u0441\u0430\u043c\u0438, \u043a\u043e\u0442\u043e\u0440\u044b\u0435 \u043f\u0440\u0438\u043d\u0438\u043c\u0430\u044e\u0442 \u0443\u0447\u0430\u0441\u0442\u0438\u0435 \u0432 \u043a\u043e\u043d\u0435\u0447\u043d\u043e\u043c \u0438\u043c\u043c\u0443\u043d\u043d\u043e\u043c \u043e\u0442\u0432\u0435\u0442\u0435. \u0411\u043e\u043b\u0435\u0435 5 % \u0441\u043e\u0432\u0440\u0435\u043c\u0435\u043d\u043d\u043e\u0433\u043e \u043d\u0430\u0441\u0435\u043b\u0435\u043d\u0438\u044f \u0438\u043c\u0435\u0435\u0442 \u0433\u0435\u043d\u0435\u0442\u0438\u0447\u0435\u0441\u043a\u0443\u044e \u043f\u0440\u0435\u0434\u0440\u0430\u0441\u043f\u043e\u043b\u043e\u0436\u0435\u043d\u043d\u043e\u0441\u0442\u044c \u043a \u0446\u0435\u043b\u0438\u0430\u043a\u0438\u0438.<\/p>\n<p>\u041f\u0440\u0435\u0434\u0440\u0430\u0441\u043f\u043e\u043b\u043e\u0436\u0435\u043d\u043d\u043e\u0441\u0442\u044c \u043a \u0446\u0435\u043b\u0438\u0430\u043a\u0438\u0438 \u043d\u0435\u0441\u0443\u0442 \u0432 \u0441\u0435\u0431\u0435 \u0433\u0435\u043d\u044b HLA-DQ2 \u0438 HLA-DQ8. \u0421\u043e\u043e\u0442\u0432\u0435\u0442\u0441\u0442\u0432\u0435\u043d\u043d\u043e, \u0435\u0441\u043b\u0438 \u0430\u043d\u0430\u043b\u0438\u0437 \u043f\u043e\u043a\u0430\u0437\u044b\u0432\u0430\u0435\u0442, \u0447\u0442\u043e \u0443 \u043e\u0431\u0441\u043b\u0435\u0434\u0443\u0435\u043c\u043e\u0433\u043e \u0447\u0435\u043b\u043e\u0432\u0435\u043a\u0430 \u043d\u0435\u0442 \u044d\u0442\u0438\u0445 \u0433\u0435\u043d\u043e\u0432 \u2013 \u0437\u043d\u0430\u0447\u0438\u0442, \u043e\u043d \u043d\u0435 \u043c\u043e\u0436\u0435\u0442 \u0431\u043e\u043b\u0435\u0442\u044c \u0446\u0435\u043b\u0438\u0430\u043a\u0438\u0435\u0439 \u0438 \u043d\u0435\u0442 \u043d\u0438\u043a\u0430\u043a\u043e\u0439 \u043d\u0435\u043e\u0431\u0445\u043e\u0434\u0438\u043c\u043e\u0441\u0442\u0438 \u043f\u043e\u0434\u0432\u0435\u0440\u0433\u0430\u0442\u044c \u0435\u0433\u043e \u0434\u0430\u043b\u044c\u043d\u0435\u0439\u0448\u0435\u043c\u0443 \u043e\u0431\u0441\u043b\u0435\u0434\u043e\u0432\u0430\u043d\u0438\u044e.<\/p>\n<p>\u0421 \u0434\u0440\u0443\u0433\u043e\u0439 \u0441\u0442\u043e\u0440\u043e\u043d\u044b, \u043e\u0431\u043d\u0430\u0440\u0443\u0436\u0435\u043d\u0438\u0435 \u0443\u043a\u0430\u0437\u0430\u043d\u043d\u044b\u0445 \u0433\u0435\u043d\u043e\u0432 \u043d\u0435 \u043e\u0437\u043d\u0430\u0447\u0430\u0435\u0442, \u0447\u0442\u043e \u0447\u0435\u043b\u043e\u0432\u0435\u043a \u043d\u0435\u043f\u0440\u0435\u043c\u0435\u043d\u043d\u043e \u0431\u043e\u043b\u0435\u043d \u0446\u0435\u043b\u0438\u0430\u043a\u0438\u0435\u0439. \u0418\u0445 \u043d\u0430\u043b\u0438\u0447\u0438\u0435 \u043e\u0437\u043d\u0430\u0447\u0430\u0435\u0442 \u043b\u0438\u0448\u044c, \u0447\u0442\u043e \u0443 \u043e\u0431\u0441\u043b\u0435\u0434\u0443\u0435\u043c\u043e\u0433\u043e \u0435\u0441\u0442\u044c \u043f\u0440\u0435\u0434\u0440\u0430\u0441\u043f\u043e\u043b\u043e\u0436\u0435\u043d\u043d\u043e\u0441\u0442\u044c \u043a \u0435\u0435 \u0440\u0430\u0437\u0432\u0438\u0442\u0438\u044e \u0438 \u0447\u0442\u043e \u0434\u043b\u044f \u043f\u043e\u0441\u0442\u0430\u043d\u043e\u0432\u043a\u0438 \u043e\u043a\u043e\u043d\u0447\u0430\u0442\u0435\u043b\u044c\u043d\u043e\u0433\u043e \u0434\u0438\u0430\u0433\u043d\u043e\u0437\u0430 \u0435\u043c\u0443 \u043d\u0435\u043e\u0431\u0445\u043e\u0434\u0438\u043c \u0433\u0438\u0441\u0442\u043e\u043b\u043e\u0433\u0438\u0447\u0435\u0441\u043a\u0438\u0439 \u0430\u043d\u0430\u043b\u0438\u0437 \u0442\u043a\u0430\u043d\u0435\u0439 \u0442\u043e\u043d\u043a\u043e\u0433\u043e \u043a\u0438\u0448\u0435\u0447\u043d\u0438\u043a\u0430.<\/p>\n<p>\u0410\u043d\u0430\u043b\u0438\u0437 \u043e\u0431\u043b\u0430\u0434\u0430\u0435\u0442 \u0432\u044b\u0441\u043e\u043a\u043e\u0439 \u0447\u0443\u0432\u0441\u0442\u0432\u0438\u0442\u0435\u043b\u044c\u043d\u043e\u0441\u0442\u044c\u044e, \u0445\u043e\u0442\u044f \u0438 \u043d\u0435 \u0438\u043c\u0435\u0435\u0442 100-\u043f\u0440\u043e\u0446\u0435\u043d\u0442\u043d\u0443\u044e \u0441\u043f\u0435\u0446\u0438\u0444\u0438\u0447\u043d\u043e\u0441\u0442\u044c \u2013 \u0434\u0430\u043d\u043d\u044b\u0435 \u0433\u0435\u043d\u044b \u0442\u0430\u043a\u0436\u0435 \u043c\u043e\u0433\u0443\u0442 \u0433\u043e\u0432\u043e\u0440\u0438\u0442\u044c \u043e \u043f\u0440\u0435\u0434\u0440\u0430\u0441\u043f\u043e\u043b\u043e\u0436\u0435\u043d\u043d\u043e\u0441\u0442\u0438 \u0438 \u043a \u0434\u0440\u0443\u0433\u0438\u043c \u043f\u0430\u0442\u043e\u043b\u043e\u0433\u0438\u044f\u043c. \u0418\u0441\u0441\u043b\u0435\u0434\u043e\u0432\u0430\u043d\u0438\u0435 \u043f\u0440\u0435\u0434\u0441\u0442\u0430\u0432\u043b\u044f\u0435\u0442 \u0441\u043e\u0431\u043e\u0439 \u0443\u0434\u043e\u0431\u043d\u044b\u0439 \u0441\u043f\u043e\u0441\u043e\u0431 \u0434\u0438\u0430\u0433\u043d\u043e\u0441\u0442\u0438\u043a\u0438, \u0442.\u043a. \u043d\u0435 \u0442\u0440\u0435\u0431\u0443\u0435\u0442, \u0432 \u043e\u0442\u043b\u0438\u0447\u0438\u0435 \u043e\u0442 \u0433\u0438\u0441\u0442\u043e\u043b\u043e\u0433\u0438\u0438, \u0441\u043b\u043e\u0436\u043d\u043e\u0433\u043e \u043f\u043e\u043b\u0443\u0447\u0435\u043d\u0438\u044f \u0431\u0438\u043e\u043c\u0430\u0442\u0435\u0440\u0438\u0430\u043b\u0430. \u042d\u0442\u043e\u0442 \u043c\u0435\u0442\u043e\u0434 \u043e\u0441\u043e\u0431\u0435\u043d\u043d\u043e \u043f\u043e\u043b\u0435\u0437\u0435\u043d, \u0435\u0441\u043b\u0438 \u0438\u043c\u0435\u044e\u0442\u0441\u044f \u043e\u0441\u043d\u043e\u0432\u0430\u043d\u0438\u044f \u043f\u043e\u0434\u043e\u0437\u0440\u0435\u0432\u0430\u0442\u044c \u043d\u0435\u043f\u0435\u0440\u0435\u043d\u043e\u0441\u0438\u043c\u043e\u0441\u0442\u044c \u0433\u043b\u044e\u0442\u0435\u043d\u0430, \u043d\u043e \u0442\u0435\u0441\u0442\u044b \u043a\u0440\u043e\u0432\u0438 \u043d\u0430 \u0430\u043d\u0442\u0438\u0442\u0435\u043b\u0430 \u043e\u0442\u0440\u0438\u0446\u0430\u0442\u0435\u043b\u044c\u043d\u044b, \u0430 \u0431\u0438\u043e\u043f\u0441\u0438\u044f \u043d\u0435\u0436\u0435\u043b\u0430\u0442\u0435\u043b\u044c\u043d\u0430 (\u0432\u0432\u0438\u0434\u0443 \u043d\u0435\u0443\u0434\u043e\u0431\u0441\u0442\u0432\u0430 \u0438\u043b\u0438 \u043d\u0435\u043f\u0435\u0440\u0435\u043d\u043e\u0441\u0438\u043c\u043e\u0441\u0442\u0438 \u043f\u0440\u043e\u0446\u0435\u0434\u0443\u0440\u044b).<\/p>\n<p><strong>\u0414\u043b\u044f \u0447\u0435\u0433\u043e \u0438\u0441\u043f\u043e\u043b\u044c\u0437\u0443\u0435\u0442\u0441\u044f \u0438\u0441\u0441\u043b\u0435\u0434\u043e\u0432\u0430\u043d\u0438\u0435?\u00a0 <\/strong>\u0414\u043b\u044f \u043e\u043f\u0440\u0435\u0434\u0435\u043b\u0435\u043d\u0438\u044f \u043f\u0440\u0435\u0434\u0440\u0430\u0441\u043f\u043e\u043b\u043e\u0436\u0435\u043d\u043d\u043e\u0441\u0442\u0438 \u043a \u0446\u0435\u043b\u0438\u0430\u043a\u0438\u0438.<\/p>\n<p><strong>\u041a\u043e\u0433\u0434\u0430 \u043d\u0430\u0437\u043d\u0430\u0447\u0430\u0435\u0442\u0441\u044f \u0438\u0441\u0441\u043b\u0435\u0434\u043e\u0432\u0430\u043d\u0438\u0435?<\/strong><\/p>\n<p>\u0412 \u0441\u043e\u043c\u043d\u0438\u0442\u0435\u043b\u044c\u043d\u044b\u0445 \u0441\u043b\u0443\u0447\u0430\u044f\u0445 \u043f\u0440\u0438 \u0443\u0441\u0442\u0430\u043d\u043e\u0432\u043b\u0435\u043d\u0438\u0438 \u0434\u0438\u0430\u0433\u043d\u043e\u0437\u0430 &#8220;\u0446\u0435\u043b\u0438\u0430\u043a\u0438\u044f&#8221; (\u043e\u0431\u043d\u0430\u0440\u0443\u0436\u0435\u043d\u0438\u0435 \u0433\u0430\u043f\u043b\u043e\u0442\u0438\u043f\u043e\u0432 HLA DQ2, DQ8 \u0434\u0435\u043b\u0430\u0435\u0442 \u0434\u0438\u0430\u0433\u043d\u043e\u0437 \u0431\u043e\u043b\u0435\u0435 \u0432\u0435\u0440\u043e\u044f\u0442\u043d\u044b\u043c, \u0430 \u0438\u0445 \u043e\u0442\u0441\u0443\u0442\u0441\u0442\u0432\u0438\u0435 \u043f\u043e\u0437\u0432\u043e\u043b\u044f\u0435\u0442 \u0441\u043d\u044f\u0442\u044c \u043f\u043e\u0434\u043e\u0437\u0440\u0435\u043d\u0438\u0435).<\/p>\n<p><strong>\u0427\u0442\u043e \u043e\u0437\u043d\u0430\u0447\u0430\u044e\u0442 \u0440\u0435\u0437\u0443\u043b\u044c\u0442\u0430\u0442\u044b?<\/strong><\/p>\n<p>\u0420\u0435\u0444\u0435\u0440\u0435\u043d\u0441\u043d\u044b\u0435 \u0437\u043d\u0430\u0447\u0435\u043d\u0438\u044f: \u0433\u0430\u043f\u043b\u043e\u0442\u0438\u043f \u0440\u0438\u0441\u043a\u0430 \u0446\u0435\u043b\u0438\u0430\u043a\u0438\u0438 HLADQ2\/DQ8 \u043d\u0435 \u043e\u0431\u043d\u0430\u0440\u0443\u0436\u0435\u043d.<\/p>\n<p>\u0423\u043a\u0430\u0437\u044b\u0432\u0430\u0435\u0442\u0441\u044f \u043d\u0430\u043b\u0438\u0447\u0438\u0435 \u0438\u043b\u0438 \u043e\u0442\u0441\u0443\u0442\u0441\u0442\u0432\u0438\u0435 \u0430\u043b\u043b\u0435\u043b\u0435\u0439 \u043f\u0440\u0435\u0434\u0440\u0430\u0441\u043f\u043e\u043b\u043e\u0436\u0435\u043d\u043d\u043e\u0441\u0442\u0438 \u043a \u0446\u0435\u043b\u0438\u0430\u043a\u0438\u0438.<\/p>","protected":false},"featured_media":0,"comment_status":"closed","ping_status":"closed","template":"","meta":[],"product_brand":[],"product_cat":[968,969],"product_tag":[],"class_list":{"0":"post-9944","1":"product","2":"type-product","3":"status-publish","5":"product_cat-teste-de-biologie-moleculara","6":"product_cat-teste-de-genetica-umana","8":"first","9":"instock","10":"sold-individually","11":"shipping-taxable","12":"purchasable","13":"product-type-simple"},"_links":{"self":[{"href":"https:\/\/old.synevo.md\/ru\/wp-json\/wp\/v2\/product\/9944","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/old.synevo.md\/ru\/wp-json\/wp\/v2\/product"}],"about":[{"href":"https:\/\/old.synevo.md\/ru\/wp-json\/wp\/v2\/types\/product"}],"replies":[{"embeddable":true,"href":"https:\/\/old.synevo.md\/ru\/wp-json\/wp\/v2\/comments?post=9944"}],"wp:attachment":[{"href":"https:\/\/old.synevo.md\/ru\/wp-json\/wp\/v2\/media?parent=9944"}],"wp:term":[{"taxonomy":"product_brand","embeddable":true,"href":"https:\/\/old.synevo.md\/ru\/wp-json\/wp\/v2\/product_brand?post=9944"},{"taxonomy":"product_cat","embeddable":true,"href":"https:\/\/old.synevo.md\/ru\/wp-json\/wp\/v2\/product_cat?post=9944"},{"taxonomy":"product_tag","embeddable":true,"href":"https:\/\/old.synevo.md\/ru\/wp-json\/wp\/v2\/product_tag?post=9944"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}