Otoimmün hastalıklar otoantikor üretimi ve doku yıkımı ile karakterize olup kalıtsal ve çevresel faktörlerden etkilenmektedir. Çölyak hastalığı genetik olarak yatkın olan bireylerde diyetle alınan glutene karşı duyarlılık sonucunda ortaya çıkan immünolojik olarak gelişen inflamatuvar yanıt sonucu intestinal villuslarda hasar ve klinik olarak malabsorpsiyona neden olan kronik otoimmün bir hastalıktır. İnflamasyon sürecien spesifik antikor üretimi eşilik eder ve gastrointestinal semptomlarla birlikte çeşitli bağırsak dışı semptomlara yol açar. Hastalığın dünyadaki prevalansının %1 olduğu tahmin edilmekle birlikte hastalığın tanısında kullanılan duyarlı ve spesifik testlerinin kullanılması nedeniyle bildirilen vaka sayısı gün geçtikçe artmaktadır. Hastalığın temelinde insan lökosit antijeni (HLA)-DQA1/B1 lokuslarındaki allellerle kodlanan HLA sınıf II protein moleküllerinin olduğu bilinmektedir. Klinik testlerde moleküler teşhis yöntemlerinde en çok HLA- DQA1/ DQB1, HLA-DRB1, HLA-DRA, CTLA4 ve MYO9B gen bölgeleri taranmaktadır. Hastalığın tedavisinde farmakolojik bir yaklaşım bulunmamakla birlikte, glutensiz diyet etkin olarak kabul edilen tek tedavi yöntemidir. Alternatif veya destekleyici bir tedavi yönteminin bulunması için preklinik ve klinik olarak oral endopeptidazlar, transglutaminaz inhibitörleri, glukokortikoidler, mikrobiyota ilişkili tedaviler, gluten bağlayıcı polimerler, immünomodülatör peptitler gibi farklı tedaviler denenmektedir. Glutene karşı bağışıklık toleransını yeniden sağlamak veya gluten kaynaklı bağışıklık aktivasyonu engellemek amacıyla potansiyel terapötik ajanların araştırmaları devam etmektedir. Yazılan derlemede çölyak hastalarına yönelik etkili bir terapötik yaklaşım bulmak amacıyla, literatürde yer alan güncel çalışmalar gözden geçirilmiştir.
Anahtar Kelimeler: Çölyak hastalığı; otoimmünite; genetik test; ilaç tedavisi
Autoimmune diseases are characterized by autoantibody production and tissue destruction and are affected by hereditary and environmental factors. Celiac disease is a chronic autoimmune disease that causes damage to intestinal villi and clinical malabsorption as a result of an immunologically developed inflammatory response resulting from sensitivity to dietary gluten in individuals who are genetically predisposed. The inflammatory process is accompanied by the production of specific antibodies and causes a variety of extra-intestinal symptoms along with gastrointestinal symptoms. Although the prevalence of the disease in the world is estimated at 1%, the number of reported cases is increasing day by day due to the use of sensitive and specific tests in the diagnosis of the disease. It is known that HLA class II protein molecules encoded by the alleles in the human leukocyte antigen (HLA)-DQA1/B1 loci are the basis of the disease. In clinical tests, molecular diagnostic methods mostly scan the HLA-DQA1/DQB1, HLA-DRB1, HLA-DRA, CTLA4, and MYO9B gene regions. Although there is no pharmacological approach to the treatment of the disease, a gluten-free diet is the only effective treatment method. In order to find an alternative or supportive treatment method, different treatments such as oral endopeptidases, transglutaminase inhibitors, glucocorticoids, microbiota-related treatments, gluten-binding polymers, and immunomodulatory peptides are tried both preclinically and clinically. Research continues for potential therapeutic agents to restore immune tolerance to gluten or to inhibit gluten-induced immune activation. In this review, current studies in the literature were reviewed in order to find an effective therapeutic approach for celiac patients.
Keywords: Celiac disease; autoimmunity; genetic testing; drug therapy
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