Autoimmune manifestations among 461 patients with monogenic inborn errors of immunity.

Journal: Pediatric Allergy And Immunology : Official Publication Of The European Society Of Pediatric Allergy And Immunology

Published: November 11, 2020

Abstract

Background: The inborn errors of immunity (IEIs) are a group of heterogeneous disorders mainly characterized by severe and recurrent infections besides other complications including autoimmune and inflammatory diseases. In this study, we aim to evaluate clinical, immunologic, and molecular data of monogenic IEI patients with and without autoimmune manifestations.

Methods: We have retrospectively screened cases of monogenic IEI in the Iranian PID registry for the occurrence of autoimmunity and immune dysregulation. A questionnaire was filled for all qualified patients with monogenic defects to evaluate demographic, laboratory, clinical, and molecular data.

Results: A total of 461 monogenic IEI patients (290 male and 171 female) with a median (IQR) age of 11.0 (6.0-20.0) years were enrolled in this study. Overall, 331 patients (72.1%) were born to consanguineous parents. At the time of the study, 330 individuals (75.7%) were alive and 106 (24.3%) were deceased. Autoimmunity was reported in 92 (20.0%) patients with a median (IQR) age at autoimmune diagnosis of 4.0 (2.0-7.0) years. Sixteen patients (3.5%) showed autoimmune complications (mostly autoimmune cytopenia) as the first presentation of the disease. Most of the patients with autoimmunity were diagnosed clinically with common variable immunodeficiency (42.4%). The frequency of sinusitis and splenomegaly was significantly higher in patients with autoimmunity than patients without autoimmunity. In patients with autoimmunity, the most common pathogenic variants were identified in LRBA (in 21 patients, 23.0%), ATM (in 13 patients, 14.0%), and BTK (in 9 patients, 10.0%) genes. In the evaluation of autoimmunity by different genes, 4 of 4 IL10RB (100%), 3 of 3 AIRE (100%), and 21 of 30 LRBA (70.0%) mutated genes had the highest prevalence of autoimmunity.

Conclusions: Autoimmune phenomena are common features among patients with monogenic IEI and are associated with a more complicated course of the disease. Therefore, when encountering autoimmune disorders, especially in the setting of dysgammaglobulinemia, it would be appropriate to conduct next-generation sequencing to discover responsible genes for the immune dysregulation at an early stage of the disease.

Authors

Gholamreza Azizi, Marzieh Tavakol, Reza Yazdani, Samaneh Delavari, Tannaz Moeini Shad, Seyed Rasouli, Mahnaz Jamee, Salar Pashangzadeh, Arash Kalantari, Mansoureh Shariat, Alireza Shafiei, Javad Mohammadi, Gholamreza Hassanpour, Zahra Chavoshzadeh, Seyed Mahdaviani, Tooba Momen, Nasrin Behniafard, Mohammad Nabavi, Mohammad Bemanian, Saba Arshi, Rasol Molatefi, Roya Sherkat, Afshin Shirkani, Soheila Alyasin, Farahzad Jabbari Azad, Javad Ghaffari, Mehrnaz Mesdaghi, Hamid Ahanchian, Maryam Khoshkhui, Mohammad Eslamian, Taher Cheraghi, Abbas Dabbaghzadeh, Rasoul Nasiri Kalmarzi, Hossein Esmaeilzadeh, Javad Tafaroji, Abbas Khalili, Mahnaz Sadeghi Shabestari, Sepideh Darougar, Mojgan Moghtaderi, Akefeh Ahmadiafshar, Behzad Shakerian, Marzieh Heidarzadeh, Babak Ghalebaghi, Seyed Fathi, Behzad Darabi, Morteza Fallahpour, Azam Mohsenzadeh, Sarehsadat Ebrahimi, Samin Sharafian, Ahmad Vosughimotlagh, Mitra Tafakoridelbari, Maziyar Rahimi Haji Abadi, Parisa Ashournia, Anahita Razaghian, Arezou Rezaei, Fereshte Salami, Paniz Shirmast, Nasrin Bazargan, Setareh Mamishi, Hossein Khazaei, Babak Negahdari, Sima Shokri, Seyed Nabavizadeh, Saeed Bazregari, Ramin Ghasemi, Shiva Bayat, Hamid Eshaghi, Nima Rezaei, Hassan Abolhassani, Asghar Aghamohammadi

Relevant Conditions

Common Variable Immune Deficiency

Autoimmune manifestations among 461 patients with monogenic inborn errors of immunity.

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