Lökosit Adezyon Defekti (Tip I ve Tip III) Tanısıyla İzlenen 14 Hastanın Klinik, İmmünolojik Özellikleri ve Tedavi Sonuçlarının Değerlendirilmesi

Year 2020, Volume: 14 Issue: 4, 286 - 294, 26.06.2020

Zehra Şule Haskoloğlu Sevgi Köstel Bal Candan İslamoğlu Avniye Baskın Dilara Beşli Caner Aytekin Figen Doğu Aydan İkincioğulları

https://doi.org/10.12956/tchd.685332

Abstract

Giriş-Amaç: Lökosit Adezyon Defekti (LAD), lökositlerin adezyon, migrasyon, kemotaksis ve ekstravazasyonunda rol alan moleküllerin eksikliklerine bağlı gelişen, nadir görülen, otozomal resesif katılımlı, üç ayrı tipi olan (LAD-I, LAD-II ve LAD-III) bir primer immün yetmezlik hastalığıdır. Tekrarlayan bakteriyel, fungal enfeksiyonlar ve lökositoz ile karakterizedir. Bu çalışmada, LAD-I ve LAD-III tanısı konulan hastaların klinik, immünolojik özelliklerinin, tedavi ve hematopoietik kök hücre nakli (HKHN) sonuçlarının değerlendirilmesi amaçlanmıştır.
Gereç ve Yöntem: Bu çalışmaya, Mart 2008 ile Haziran 2018 tarihleri arasında bölümümüzde LAD tanısı konulan, takip ve tedavileri yapılan 14 hasta dâhil edildi. Hastaların demografik, klinik, laboratuvar özellikleri, genetik mutasyonları, izlemleri ve HKHN sonuçları geriye dönük olarak değerlendirildi.
Bulgular: Hastaların 12’si LAD-I (%86), 2’si LAD-III (%14) idi. Tüm hastalarda (9 kız/5 erkek) akraba evliliği, 3 hastada benzer şikâyetlerle kaybedilen kardeş öyküsü vardı. Göbek bağının düşmesinde gecikme 13/14(%93), omfalit 12/14(%86), nekrotizan cilt yaraları 9/14(%64), pnömoni 5/14(%36), gingivit 4/14(%29) ve moniliazis 4/14(%29) en sık rastlanan klinik bulgulardı. Tüm hastalarda lökositoz ve nötrofili mevcuttu. CD18 ekspresyonu %2’den düşük olan 10 hasta ağır LAD-I, CD18 ekspresyonları %16 ve %19 olan 2 hasta ise hafif-orta ağırlıkta LAD-I olarak değerlendirildi. 8 hastada mutasyonlar genetik analiz ile gösterildi. Kardeş olan 3 hastada ITGB2 geninde yeni bir mutasyon saptandı. Nakil yapılmayan hastalar, tekrarlayan cilt ve solunum enfeksiyonları nedeniyle çok kez ayaktan veya hastanede yatarak tedavi aldı. En sık rastlanan enfeksiyon ajanları S.aureus ve E.faecium oldu. 6 hastaya tam uyumlu aile içi ve 1 hastaya tam uyumlu akraba dışı donörden HKHN yapıldı. Tüm hastalarda engrafman sağlandı ve ciddi bir komplikasyon izlenmedi. LAD-III tanılı bir olgu nakil yapılamadan kanama nedeniyle kaybedildi. Tüm hastalarda hayatta kalma oranı %93 iken HKHN yapılanlarda %100 oldu.
Sonuç: Göbek bağının düşmesinde gecikme, tekrarlayan cilt ve mukoza enfeksiyonları olan ve lökositozla gelen her olguda LAD tanısı akla gelmelidir. Hematopoetik kök hücre nakli bu hastalar için küratif tedavi yöntemidir.


Abstract
Introduction-Aim
Leukocyte Adhesion Deficiency (LAD) is a rare autosomal recessive primary immunodeficiency that is due to deficiencies of molecules involved in adhesion, migration, chemotaxis and extravasation of leukocytes with three different types (LAD-I, LAD-II, LAD-III). It is characterised by recurrent bacterial, fungal infections and leucocytosis. In this study, it is aimed to evaluate clinical, immunological features, treatment and follow-up of patients diagnosed with LAD-I and III.

Material-Method
In this study there were 14 LAD patients who were diagnosed, treated and followed up in our department between March 2008- June 2018. The demographic, clinical, laboratory features, genetic mutations, follow-up and hematopoietic stem cell transplantation (HSCT) results of patients were evaluated retrospectively.

Results
There were 12 (86%) patients with LAD-I, and 2 (14%) of them were LAD-III. All patients (9 female/5 male) had consanguinity, 3 patients had history of sibling death with similar complaints. The most common clinical findings were 13 (93%) delayed umbilical cord separation, 12 (86%) omphalitis, 9 (64%) necrotising skin wounds, 5 (36%) pneumonia, 4 (29%) gingivitis and 4 (29%) moniliasis. All patients had neutrophilia and leucocytosis. There were 10 severe LAD-I patients with CD18 expression lower than 2% and 2 mild-moderate LAD-I patients with CD18 expression 16% and 19%. Mutations were demonstrated in 8 patients by genetic analysis. A new mutation in the ITGB2 gene was detected in 3 sibling patients. Patients who were not transplanted received multiple outpatient/inpatient treatments due to recurrent skin and respiratory infections. S.aureus and E.faecium were most common infectious agents. HSCT was performed in 6 patients from full matched related donors and in 1 patient from full matched unrelated donor. Engraftment was achieved in all patients without serious complications. One patient with LAD-III died due to bleeding before transplantation. While the survival rate was 93% in all patients, it was 100% in HSCT patients.

Conclusion
LAD diagnosis must be considered in patients with delayed umbilical cord separation, recurrent skin and mucosal infections and leucocytosis. Hematopoietic stem cell transplantation is a curative treatment for these patients.

Keywords

Lökosit adezyon defekti, klinik, izlem

Supporting Institution

Bu çalışma için hiç bir kurumdan destek alınmamıştır.

Project Number

-

Thanks

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