Clinical and molecular findings in actin-related inborn errors of immunity: the middle East and North Africa registry
Makaleler > Tam Makale · 2025
Yazarlar: Zahra Chavoshzadeh, Shahrzad Fallah, Vahide Zeinali, Samin Sharafian, Samaneh Delavari, Mehrnaz Mesdaghi, Reda Djidjik, Brahim Belaid, Aydan Ikinciogullari, Sule Haskologlu, Figen Dogu, Ferah Genel, Nesrin Gulez, Safa Baris, Ahmet Ozen, Elif Karakoc-Aydiner, Ayça Kiykim, Zeynep Meric, Necil Kutukculer, Ayse Aygun, Güzide AKSU, Neslihan KARACA, Mehmet Geyik, Sevgi Keles, Ismail Reisli, Sukru Nail Guner, Rachida Boukari, Saliha Hakem, Reda Belbouab, Mohamed-Ridha Barbouche, Imen Ben-Mustapha, Najla Mekki, Meriem Ben-Ali, Ali Sobh, Marwa Elnagdy, Kamel Djenouhat, Azzeddine Tahiat, Hiba Mohammed Shendi, Amna Alkuwaiti, Gulnara Nasrullayeva, Tariq Alfars, Nashat Alsukaiti, Michel Massaad, Cybel Mehawej, Andre Megarbane, Carla Irani, Gehad Elghazali, Salem Al-Tamemi, Nisreen Khalifa, Raed Alzyoud, Sara Sebnem Kilic Gultekin, Hulya Kose, Hedieh Khodaverdy, Bibi Shahin Shamsian, Narges Eslami, Tooba Momen, Roya Sherkat, Soheila Aleyasin, Hossein Esmaeilzadeh, Hamid Ahanchian, Fereshte Salami, Saba Fekrvand, Loïc Dupre, Hans D. Ochs, Nima Rezaei, Waleed Al-Herz, Hassan Abolhassani
Frontiers in Genetics, Uluslararası, Wos, 2025, cilt 16, ss 1584681-1584681
DOI: 10.3389/fgene.2025.1584681
Özet
Background The majority of monogenic inborn errors of immunity presenting as actinopathies were reported originally from the Middle East and North Africa (MENA) countries indicating a high prevalence of these entities in the region. However, their prognosis is unclear due to rarity and lack of comprehensive treatment outcomes. Methods We evaluated clinical, immunological, and genetic abnormalities associated with 15 genetic entities of actinopathies. Based on the function of mutant genes in actin-regulatory pathways, patients were classified into CDC42- and RAC2-related subcategories. Results A total of 503 individuals (29.5% females) from 17 countries were considered with a median age of 120 months. Although most patients presented initially with allergic phenotypes (37.7%), the most prevalent manifestations throughout the lifespan were infection in respiratory tracts (72.2%). Primary clinical diagnosis was mainly combined immunodeficiencies (48.3%) and the majority of cases were molecularly assigned to the CDC42 pathway (64.8%). The most common genetic defects were reported within the DOCK8 (n = 209) followed by the WAS (n = 94) and the CARMIL2 (n = 15) genes. Hematopoietic stem cell transplantation (HSCT) was conducted on 24.0% of patients, which significantly improved survival in patients with defects in WAS, DOCK8 and DOCK2. Overall mortality was 23.0%, mainly due to sepsis and malignancy. Conclusion Patients with defects in RAC2-associated regulators of actin usually present with late-onset symptoms due to normal immune profiles, but a higher rate of EBV and HPV infections, autoimmune cytopenia, asthma, and lymphoproliferation compared to defects in the CDC42 pathway. The severity of mutations in patients of the CDC42 group helps to estimate the prognosis of the disease and prioritization of HSCT.