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

Giris-Amac: Lokosit Adezyon Defekti (LAD), lokositlerin adezyon, migrasyon, kemotaksis ve ekstravazasyonunda rol alan molekullerin eksikliklerine bagli gelisen, nadir gorulen, otozomal resesif katilimli, uc ayri tipi olan (LAD-I, LAD-II ve LAD-III) bir primer immun yetmezlik hastaligidir. Tekrarlayan bakteriyel, fungal enfeksiyonlar ve lokositoz ile karakterizedir. Bu calismada, LAD-I ve LAD-III tanisi konulan hastalarin klinik, immunolojik ozelliklerinin, tedavi ve hematopoietik kok hucre nakli (HKHN) sonuclarinin degerlendirilmesi amaclanmistir. Gerec ve Yontem: Bu calismaya, Mart 2008 ile Haziran 2018 tarihleri arasinda bolumumuzde LAD tanisi konulan, takip ve tedavileri yapilan 14 hasta dâhil edildi. Hastalarin demografik, klinik, laboratuvar ozellikleri, genetik mutasyonlari, izlemleri ve HKHN sonuclari geriye donuk olarak degerlendirildi. Bulgular: Hastalarin 12’si LAD-I (%86), 2’si LAD-III (%14) idi. Tum hastalarda (9 kiz/5 erkek) akraba evliligi, 3 hastada benzer sikâyetlerle kaybedilen kardes oykusu vardi. Gobek baginin dusmesinde gecikme 13/14(%93), omfalit 12/14(%86), nekrotizan cilt yaralari 9/14(%64), pnomoni 5/14(%36), gingivit 4/14(%29) ve moniliazis 4/14(%29) en sik rastlanan klinik bulgulardi. Tum hastalarda lokositoz ve notrofili mevcuttu. CD18 ekspresyonu %2’den dusuk olan 10 hasta agir LAD-I, CD18 ekspresyonlari %16 ve %19 olan 2 hasta ise hafif-orta agirlikta LAD-I olarak degerlendirildi. 8 hastada mutasyonlar genetik analiz ile gosterildi. Kardes olan 3 hastada ITGB2 geninde yeni bir mutasyon saptandi. Nakil yapilmayan hastalar, tekrarlayan cilt ve solunum enfeksiyonlari nedeniyle cok kez ayaktan veya hastanede yatarak tedavi aldi. En sik rastlanan enfeksiyon ajanlari S.aureus ve E.faecium oldu. 6 hastaya tam uyumlu aile ici ve 1 hastaya tam uyumlu akraba disi donorden HKHN yapildi. Tum hastalarda engrafman saglandi ve ciddi bir komplikasyon izlenmedi. LAD-III tanili bir olgu nakil yapilamadan kanama nedeniyle kaybedildi. Tum hastalarda hayatta kalma orani %93 iken HKHN yapilanlarda %100 oldu. Sonuc: Gobek baginin dusmesinde gecikme, tekrarlayan cilt ve mukoza enfeksiyonlari olan ve lokositozla gelen her olguda LAD tanisi akla gelmelidir. Hematopoetik kok hucre nakli bu hastalar icin kuratif tedavi yontemidir. 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.