{"id":13356,"date":"2023-03-03T17:09:36","date_gmt":"2023-03-03T14:09:36","guid":{"rendered":"http:\/\/blog.ulubat.org\/?p=13356"},"modified":"2023-03-03T17:09:39","modified_gmt":"2023-03-03T14:09:39","slug":"lokosit-adezyon-defekti-lad","status":"publish","type":"post","link":"https:\/\/blog.ulubat.org\/index.php\/genel\/lokosit-adezyon-defekti-lad\/","title":{"rendered":"L\u00d6KOS\u0130T ADEZYON DEFEKT\u0130 (LAD)"},"content":{"rendered":"\n<figure class=\"wp-block-pullquote\"><blockquote><p>\u00d6ncelikle 6 \u015eubat 2023 depremlerinde zarar g\u00f6ren herkesin ac\u0131s\u0131n\u0131 payla\u015f\u0131yorum ve bilimle \u015fekillenen yeni bir gelecek umut ediyorum.<\/p><\/blockquote><\/figure>\n\n\n\n<p><\/p>\n\n\n\n<p>Bu yaz\u0131m\u0131zda l\u00f6kosit adezyon defektine g\u00f6z ataca\u011f\u0131z.<\/p>\n\n\n<div class=\"wp-block-image is-style-default\">\n<figure class=\"aligncenter size-large is-resized\"><img loading=\"lazy\" src=\"https:\/\/upload.wikimedia.org\/wikipedia\/commons\/3\/38\/Staph_aureus_outside_a_white_blood_cell.jpg\" alt=\"\" width=\"705\" height=\"470\" \/><figcaption>https:\/\/upload.wikimedia.org\/wikipedia\/commons\/3\/38\/Staph_aureus_outside_a_white_blood_cell.jpg<\/figcaption><\/figure><\/div>\n\n\n<p><\/p>\n\n\n\n<h2>L\u00d6KOS\u0130T NED\u0130R?<\/h2>\n\n\n\n<p>Beyaz kan h\u00fccresi (WBC) ya da akyuvar olarak bilinen l\u00f6kositler, ba\u011f\u0131\u015f\u0131kl\u0131k sisteminin \u00f6nemli bir par\u00e7as\u0131d\u0131r. V\u00fccudu enfeksiyonlara kar\u015f\u0131 koruyan h\u00fccre grubudur. Kan\u0131n \u015fekilli elemanlar\u0131n\u0131n yaln\u0131zca %1&#8217;lik bir k\u0131sm\u0131n\u0131 olu\u015ftursalar da, v\u00fccudun yabanc\u0131 organizmalar ile kar\u015f\u0131la\u015fmas\u0131 durumunda h\u0131zla \u00e7o\u011fal\u0131rlar ve g\u00f6\u00e7 ederler. Asl\u0131nda bir \u00e7e\u015fit gizli \u00f6zel tim olarak d\u00fc\u015f\u00fcnebiliriz. Genel olarak 5 alt gruba ay\u0131rd\u0131\u011f\u0131m\u0131z l\u00f6kositlerin farkl\u0131 i\u015flevleri vard\u0131r. K\u0131saca bu alt gruplar\u0131 tan\u0131mam\u0131z gerekirse: <\/p>\n\n\n\n<p><strong>N\u00f6trofiller:<\/strong>&nbsp;K\u0131saltmas\u0131 NEU olan&nbsp;ve v\u00fccutta enfeksiyona sebep olan yabanc\u0131 organizmalar\u0131n yan\u0131na ilk ula\u015fan \u00f6nc\u00fc h\u00fccrelerdir. N\u00f6trofiller, yabanc\u0131 organizmalarla sava\u015fmak i\u00e7in kimyasal enzimleri serbest b\u0131rak\u0131r&nbsp;ve onlar\u0131 sindirir. N\u00f6trofiller lok\u00f6sit grubunun %55 ile %70&#8217;ini olu\u015fturur.<\/p>\n\n\n\n<p><strong>Lenfositler:<\/strong> Lenf dokusunda ve kemik ili\u011finde bulunurlar. LYM olarak k\u0131salt\u0131lan lenfosit h\u00fccreleri, kemik ili\u011fi taraf\u0131ndan \u00fcretilir. Bir k\u0131sm\u0131 \u00fcretildi\u011fi b\u00f6lgede kalarak B h\u00fccrelerine d\u00f6n\u00fc\u015f\u00fcr. B\u00fcy\u00fck b\u00f6l\u00fcm\u00fc ise tim\u00fcs olarak adland\u0131r\u0131lan lenf bezine giderek, T h\u00fccrelerine d\u00f6n\u00fc\u015f\u00fcr. Daha sonra bademcik, dalak, ba\u011f\u0131rsak ve lenf bezleri gibi lenfoid dokulara yay\u0131l\u0131r. Lenfositler edinilmi\u015f imm\u00fcn yan\u0131tta g\u00f6rev al\u0131rlar.<\/p>\n\n\n\n<p><strong>Monositler ve Makrofajlar:&nbsp;<\/strong>Akyuvarlar\u0131n yakla\u015f\u0131k %8&#8217;ini olu\u015fturan monositler, kemik ili\u011finde \u00fcretildikten sonra kana kar\u0131\u015f\u0131r. Kan dola\u015f\u0131m\u0131ndayken monosit olarak tan\u0131mlanan bu h\u00fccre yap\u0131lar\u0131, birka\u00e7 saat i\u00e7inde dola\u015f\u0131m sisteminden \u00e7\u0131karak dokulara ula\u015f\u0131r. Dokuya ula\u015fan monosit yap\u0131lar\u0131na makrofaj denir. Enfeksiyona sebep olan mikroorganizmalar\u0131 ortadan kald\u0131r\u0131r, \u00f6l\u00fc h\u00fccreleri temizlerler.<\/p>\n\n\n\n<p><strong>Eozinofiller:<\/strong> EOS olarak k\u0131salt\u0131l\u0131rlar. V\u00fccuttaki inflamasyon yani yang\u0131sal ve alerjik reaksiyonlarda rol oynarlar.<\/p>\n\n\n\n<p><strong>Bazofiller: <\/strong>V\u00fccutta yer alan l\u00f6kosit tipleri aras\u0131nda en az say\u0131da olanlard\u0131r. Enfeksiyon ve parazit kaynakl\u0131 enfeksiyon tipleri ile m\u00fccadele eder. Alerjik reaksiyonlar s\u0131ras\u0131nda histamin salg\u0131layarak, v\u00fccudun imm\u00fcnoglobulin E (Ig E) adl\u0131 antikoru \u00fcretmesini sa\u011flar. Ayr\u0131ca salg\u0131lad\u0131\u011f\u0131 heparin antikoag\u00fclan\u0131 sayesinde p\u0131ht\u0131la\u015fmay\u0131 \u00f6nleyerek kan\u0131n ak\u0131\u015fkanl\u0131\u011f\u0131n\u0131 art\u0131r\u0131r.<\/p>\n\n\n<div class=\"wp-block-image is-style-default\">\n<figure class=\"aligncenter size-large is-resized\"><img loading=\"lazy\" src=\"https:\/\/blog.ulubat.org\/wp-content\/uploads\/2023\/02\/Blausen_0909_WhiteBloodCells.png\" alt=\"\" width=\"613\" height=\"460\" \/><figcaption>https:\/\/upload.wikimedia.org\/wikipedia\/commons\/1\/1f\/Blausen_0909_WhiteBloodCells.png<\/figcaption><\/figure><\/div>\n\n\n<h2>L\u00d6KOS\u0130T ADEZYON DEFEKT\u0130 NED\u0130R?<\/h2>\n\n\n\n<p>L\u00f6kosit adezyon eksikli\u011fi (LAD), klinik sendromlarla sonu\u00e7lanan h\u00fccre adezyon molek\u00fcllerinin bir kusurudur. H\u00fccre adezyon molek\u00fclleri yap\u0131\u015fmay\u0131 sa\u011flayarak h\u00fccre-h\u00fccre ve h\u00fccre-ekstrasel\u00fcler matriks etkile\u015fimleriyle h\u00fccrelerde farkl\u0131la\u015fma ve \u00e7o\u011falma gibi \u00f6nemli aktivitelerin ba\u015flat\u0131lmas\u0131nda \u00f6nemli rol \u00fcstlenirler. LAD&#8217;nin 3 tipi vard\u0131r:<\/p>\n\n\n\n<p><strong>Tip 1 LAD: <\/strong>Bu tipte beta 2 integrin genindeki mutasyonlar nedeniyle kusur vard\u0131r. CD18 ekspresyonu kusurludur.<\/p>\n\n\n\n<p><em><strong>Semptomlar: <\/strong><\/em><\/p>\n\n\n\n<ul><li>G\u00f6bek kordonunun ge\u00e7 d\u00fc\u015fmesi.<\/li><li>Ya\u015fam\u0131n ilk haftalar\u0131nda ba\u015flayan tekrarlayan piyojenik enfeksiyonlar.<\/li><li>Staphylococcus aureus ve Pseudomonas aeruginosa&#8217;n\u0131n neden oldu\u011fu enfeksiyonlar.<\/li><li>\u0130rin olu\u015fumunun olmamas\u0131.<\/li><li>Di\u015f eti iltihab\u0131.<\/li><\/ul>\n\n\n\n<p><strong>Tip 2 LAD:<\/strong> LAD II&#8217;ye Golgi aparat\u0131na \u00f6zg\u00fc fukoz ta\u015f\u0131y\u0131c\u0131s\u0131ndaki mutasyonlar neden olur. Bu da selektinler i\u00e7in fukosile edilmi\u015f ligand olan Sialyl Lewis X&#8217;in yoklu\u011funa yol a\u00e7ar ve kaskad\u0131n yuvarlanma faz\u0131 sekteye u\u011frat\u0131lm\u0131\u015f olur.<\/p>\n\n\n\n<p><em><strong>Semptomlar: <\/strong><\/em><\/p>\n\n\n\n<ul><li>Tekrarlayan cilt enfeksiyonlar\u0131.<\/li><li>Pn\u00f6moni.<\/li><li>Bron\u015fektazi.<\/li><li>T\u00fcberk\u00fcloz.<\/li><li>(LAD I ile kar\u015f\u0131la\u015ft\u0131r\u0131ld\u0131\u011f\u0131nda enfeksiyonlar daha az \u015fiddetli ve daha azd\u0131r.)<\/li><\/ul>\n\n\n\n<p><strong>Tip 3 LAD:<\/strong> Bu tipte ise beta integrin 1, 2 ve 3&#8217;te bir birincil aktivasyon kusuru vard\u0131r.<\/p>\n\n\n\n<p><em><strong>Semptomlar: <\/strong><\/em><\/p>\n\n\n\n<ul><li>Omfalit.<\/li><li>Osteoporoz benzeri kemik \u00f6zellikleri.<\/li><li>Kanama komplikasyonlar\u0131.<\/li><li>Hematolojik anormallikler.<\/li><\/ul>\n\n\n\n<p>Bu k\u0131smen spesifik semptomlar\u0131n yan\u0131nda baz\u0131 di\u011fer semptomlar da vard\u0131r: Vajinit, peritonit, osteomiyelit, perianal apseler, sin\u00fczit, trakeobron\u015fit, nekrotik yumu\u015fak doku enfeksiyonlar\u0131, orta kulak iltihab\u0131, menenjit vb.<\/p>\n\n\n\n<h2>T\u0130P 1 L\u00d6KOS\u0130T ADEZYON DEFEKT\u0130NDE EP\u0130DEM\u0130YOLOJ\u0130 VE PATOF\u0130ZYOLOJ\u0130<\/h2>\n\n\n\n<p>Tip 1 LAD ya da LAD I en s\u0131k g\u00f6r\u00fclen l\u00f6kosit adezyon defekti tipidir ve g\u00f6r\u00fclme oran\u0131 1\/1.000.000&#8217;dir. Tip 1 LAD, 21q22.3&#8217;te kodlanan CD18&#8217;i kodlayan ITGB2  gen b\u00f6lgesindeki mutasyonlardan kaynaklanmaktad\u0131r.&nbsp;Bu gen; l\u00f6kosit integrinleri LFA-1, Mac 1 ve p150,95&#8217;in ortak alt birimini kodlar. Fonksiyonel bir alt \u00fcnitenin \u00fcretilememesi bu 3 l\u00f6kosit integrininin tamam\u0131n\u0131n kusurlu ekspresyonuna neden olur ve l\u00f6kositler normalin alt\u0131nda adezyon \u00f6zelliklerine sahip olurlar. T\u00fcrkiye&#8217;de 15 LAD I hastas\u0131 \u00fczerinde yap\u0131lan bir \u00e7al\u0131\u015fma T\u00fcrkiye&#8217;deki LAD I hastalar\u0131n\u0131n klinik durumlar\u0131 hakk\u0131nda baz\u0131 bilgiler vermektedir. Bu \u00e7al\u0131\u015fmada hastalar\u0131n ya\u015flar\u0131 1-48 ay aras\u0131nda de\u011fi\u015fmekle birlikte medyan\u0131 3 ayd\u0131r. 15 hastan\u0131n 11&#8217;inde ilk 6 ayda konulmu\u015f LAD I tan\u0131s\u0131 bulunmaktad\u0131r ve 15 hastan\u0131n 14&#8217;\u00fcn\u00fcn ebeveynleri akrabad\u0131r. Bu 15 hastan\u0131n %80&#8217;inde (n=12) g\u00f6bek kordonunun ge\u00e7 d\u00fc\u015fmesi vard\u0131,&nbsp;hastalar\u0131n %53&#8217;\u00fcnde (n=8) omfalit g\u00f6r\u00fcld\u00fc, &nbsp;%73&#8217;\u00fcnde (n=11) n\u00f6trofil bask\u0131nl\u0131\u011f\u0131 olan l\u00f6kositoz g\u00f6zlenmi\u015ftir. <\/p>\n\n\n\n<h2>L\u00d6KOS\u0130T ADEZYON DEFEKT\u0130NDE TEDAV\u0130 UYGULAMALARI<\/h2>\n\n\n\n<p>LAD I i\u00e7in genel tedavi y\u00f6ntemi hematopoietik k\u00f6k h\u00fccre naklidir (HSCT). \u015eiddetli seyreden LAD I&#8217;den muzdarip hastalar\u0131n 2 ya\u015f\u0131na kadar hematopoietik k\u00f6k h\u00fccre nakli olmamalar\u0131 durumunda ya\u015fama \u015fanslar\u0131 olduk\u00e7a d\u00fc\u015f\u00fckt\u00fcr. LAD I&#8217;li hastalarda \u015fiddetli di\u015f eti iltihab\u0131 ve inat\u00e7\u0131 sakral yaralar\u0131n giderilmesi ya da hafifletilmesi i\u00e7in interl\u00f6kin-23 ve interl\u00f6kin-12&#8217;nin p40 alt birimini ba\u011flayarak bu sitokinlerin aktivitesini bloke eden ve interl\u00f6kin-23&#8217;e ba\u011fl\u0131 interl\u00f6kin-17 \u00fcretimini engelleyen ustekinumab&nbsp;kullan\u0131labilir. Tip 2 LAD&#8217;de fukoz takviyesinden olumlu sonu\u00e7lar al\u0131nmaktad\u0131r. Rekombinant fakt\u00f6r VIIa&#8217;n\u0131n kullan\u0131m\u0131n\u0131n tip 3 LAD&#8217;li hastalarda olumlu sonu\u00e7lar verdi\u011fi d\u00fc\u015f\u00fcn\u00fclmektedir. <\/p>\n\n\n\n<p><\/p>\n\n\n\n<p><\/p>\n\n\n\n<p><\/p>\n\n\n\n<p><\/p>\n\n\n\n<p><\/p>\n\n\n\n<h2>KAYNAK\u00c7A:<\/h2>\n\n\n\n<p>Hanna S, Etzioni A. Leukocyte adhesion deficiencies. Ann N Y Acad Sci. 2012 Feb;1250:50-5. doi: 10.1111\/j.1749-6632.2011.06389.x. Epub 2012 Jan 25. PMID: 22276660.<\/p>\n\n\n\n<p>Cox DP, Weathers DR. Leukocyte adhesion deficiency type 1: an important consideration in the clinical differential diagnosis of prepubertal periodontitis. A case report and review of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2008 Jan;105(1):86-90. doi: 10.1016\/j.tripleo.2007.02.026. Epub 2007 Jul 6. PMID: 17618138.<\/p>\n\n\n\n<p>Yaz I, Ozbek B, Bildik HN, Tan C, Oskay Halacli S, Soyak Aytekin E, Esenboga S, Cekic S, Kilic SS, Keskin O, van Leeuwen K, Roos D, Cagdas D, Tezcan I. Clinical and laboratory findings in patients with leukocyte adhesion deficiency type I: A multicenter study in Turkey. Clin Exp Immunol. 2021 Oct;206(1):47-55. doi: 10.1111\/cei.13645. Epub 2021 Aug 5. PMID: 34310689; PMCID: PMC8446394.<\/p>\n\n\n\n<p>Almarza Novoa E, Kasbekar S, Thrasher AJ, Kohn DB, Sevilla J, Nguyen T, Schwartz JD, Bueren JA. Leukocyte adhesion deficiency-I: A comprehensive review of all published cases. J Allergy Clin Immunol Pract. 2018 Jul-Aug;6(4):1418-1420.e10. doi: 10.1016\/j.jaip.2017.12.008. Epub 2018 Jan 20. PMID: 29371071.<\/p>\n\n\n\n<p>Moutsopoulos NM, Zerbe CS, Wild T, Dutzan N, Brenchley L, DiPasquale G, Uzel G, Axelrod KC, Lisco A, Notarangelo LD, Hajishengallis G, Notarangelo LD, Holland SM. Interleukin-12 and Interleukin-23 Blockade in Leukocyte Adhesion Deficiency Type 1. N Engl J Med. 2017 Mar 23;376(12):1141-1146. doi: 10.1056\/NEJMoa1612197. PMID: 28328326; PMCID: PMC5494261.<\/p>\n\n\n\n<p>Marquardt T, L\u00fchn K, Srikrishna G, Freeze HH, Harms E, Vestweber D. Correction of leukocyte adhesion deficiency type II with oral fucose. Blood. 1999 Dec 15;94(12):3976-85. PMID: 10590041.<\/p>\n\n\n\n<p><a href=\"https:\/\/acikders.ankara.edu.tr\/pluginfile.php\/129594\/mod_resource\/content\/1\/Adezyon%201.pdf\">https:\/\/acikders.ankara.edu.tr\/pluginfile.php\/129594\/mod_resource\/content\/1\/Adezyon%201.pdf<\/a><\/p>\n\n\n\n<p><a href=\"https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK539770\/\">https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK539770\/<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Beyaz kan h\u00fccresi (WBC) ya da akyuvar olarak bilinen l\u00f6kositler, ba\u011f\u0131\u015f\u0131kl\u0131k sisteminin \u00f6nemli bir par\u00e7as\u0131d\u0131r. V\u00fccudu enfeksiyonlara kar\u015f\u0131 koruyan h\u00fccre grubudur. Kan\u0131n \u015fekilli elemanlar\u0131n\u0131n yaln\u0131zca %1\u2019lik bir k\u0131sm\u0131n\u0131 olu\u015ftursalar da, v\u00fccudun yabanc\u0131 organizmalar ile kar\u015f\u0131la\u015fmas\u0131 durumunda h\u0131zla \u00e7o\u011fal\u0131rlar ve g\u00f6\u00e7 ederler. Asl\u0131nda bir \u00e7e\u015fit gizli \u00f6zel tim olarak d\u00fc\u015f\u00fcnebiliriz. Genel olarak 5 alt gruba ay\u0131rd\u0131\u011f\u0131m\u0131z l\u00f6kositlerin farkl\u0131 i\u015flevleri vard\u0131r. K\u0131saca bu alt gruplar\u0131 tan\u0131mam\u0131z gerekirse&#8230;<\/p>\n","protected":false},"author":1139,"featured_media":13395,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":[],"categories":[1,2173],"tags":[2402,2405,73,2403,149,115,2406,2401,2404,265,66],"acf":[],"views":263,"_links":{"self":[{"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/posts\/13356"}],"collection":[{"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/users\/1139"}],"replies":[{"embeddable":true,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/comments?post=13356"}],"version-history":[{"count":10,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/posts\/13356\/revisions"}],"predecessor-version":[{"id":13507,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/posts\/13356\/revisions\/13507"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/media\/13395"}],"wp:attachment":[{"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/media?parent=13356"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/categories?post=13356"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/blog.ulubat.org\/index.php\/wp-json\/wp\/v2\/tags?post=13356"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}