Innovations in Hereditary Angioedema Pathophysiology

Hereditary angioedema (HAE) is a rare, inherited disease mostly associated with mutations in the SERPING1 gene (serpin family G member 1), which encodes the C1 inhibitor (C1- INH) protein. Regulation can lead to plasma deficiency and ensuing repeated attacks of severe angioedema. This disease was first described clinically and genetically in 1888 by William Osler, who named it “hereditary angioneurotic edema (HANE).” It took 75 years until Donaldson and Evans identified the fundamental role of C1-INH in the pathophysiology of so-called HANE by Osler. Significant progress has been made in the research of this genetic disease when the role of neural factors was documented as being too small to lead to edema, the name was changed as HAE. Therefore, the name of more than 490 different mutations have been reported in the region of the C1-INH gene (SERPING1) until mid-2018. It is now known that C1-INH deficiency overstimulates the plasma contact (kallikrein-kinin) system, which eventually results in the overproduction of bradykinin. By binding to the bradykinin B2 receptor, bradykinin increases vascular permeability (vasodilation) and causes contraction of nonvascular smooth muscle, and acts as a main/major mediator in the pathophysiology of HAE. Reports since 2000 have described a new type of HAE with “normal” CI-INH levels, primarily in Caucasians. A number of abnormalities in the genes encoding for factor XII, angiopoietin-1, and plasminogen have been identified in this novel disease entity. The establishment of treatment modalities for HAE with normal C1-INH is also expected.

Herediter Anjiyoödem Patofizyolojisinde Yenilikler

Herediter anjiyoödem (HAÖ), çoğunlukla C1 inhibitoru (C1-INH) kodlayan SERPING1 genindeki mutasyonlar sonucunda plazma düzeyinde düşmeye bağlı tekrarlayan ciddi şişme (anjiyoödem) ataklarıyla seyreden nadir görülen genetik bir bozukluktur. Bu hastalığı 1888’de klinik ve genetik olarak ilk defa herediter anjiyonörotik ödem (HANÖ) olarak adlandıran Osler tanımlamıştır. Osler tarafından HANÖ diye bildirilen hastalığın patofizyolojisinde C1-INH’in esas rolünün Donaldson ve Evans tarafından aydınlatılması 75 yılı almıştır. Bu herediter hastalığın araştırılmasında önemli derecede gelişme, ismindeki nörotik kelimesinin sinirsel faktörlerin ödeme katkısının çok az olduğunun anlaşılarak çıkartılması ve isminin HAÖ olarak değişmesiyle sağlanmıştır. 2018’in ortası itibarıyla, C1-INH (SERPINGI) geninde 490’den fazla değişik mutasyon bildirilmiştir. Günümüzde C1-INH eksikliğinin plazma kontakt (kallikrein-kinin) sisteminin aktivasyonuna ve nihai olarak bradikinin aşırı üretimine yol açtığı bilinmektedir. Bradikinin, bradikinin B2 reseptörüne bağlanarak, vasküler permeabiliteyi artırır (vazodilatasyon), damar dışı düz kasları kasar ve HAÖ patofizyolojisinde ana mediatör gibi rol oynar. 2000 yılı sonrasında, HAÖ hastalığı hakkındaki en yeni gelişme, C1-INH’in düzeyinin “normal” olduğu yeni bir HAÖ tipinin beyaz ırkta bildirilmesidir. Faktör XII, anjiyopoietin-1 ve plazminojen gibi birkaç gende anomali hastalığın bu yeni tipinde tanımlanmıştır. C1-INH’in “normal” olduğu HAÖ tiplerinde tedavi şekillerinin belirlenmesi beklenmektedir.

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Kaynak Göster

Southern Clinics of Istanbul Eurasia
  • ISSN: 2587-0998
  • Yayın Aralığı: Yılda 4 Sayı
  • Başlangıç: 2017

652117

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