Autoimmune manifestations among 461 patients with monogenic inborn errors of immunity
Authors: Azizi Gholamreza , Tavakol Marzieh , Yazdani Reza , Delavari Samaneh , Moeini Shad Tannaz , Rasouli Seyed Erfan , Jamee Mahnaz , Pashangzadeh Salar , Kalantari Arash , Shariat Mansoureh , Shafiei Alireza , Mohammadi Javad , Hassanpour Gholamreza , Chavoshzadeh Zahra , Mahdaviani Seyed Alireza , Momen Tooba , Behniafard Nasrin , Nabavi Mohammad , Bemanian Mohammad Hassan , Arshi Saba , Molatefi Rasol , Sherkat Roya , Shirkani Afshin , Alyasin Soheila , Jabbari‐Azad Farahzad , Ghaffari Javad , Mesdaghi Mehrnaz , Ahanchian Hamid , Khoshkhui Maryam , Eslamian Mohammad Hossein , Cheraghi Taher , Dabbaghzadeh Abbas , Nasiri Kalmarzi Rasoul , Esmaeilzadeh Hossein , Tafaroji Javad , Khalili Abbas , Sadeghi‐Shabestari Mahnaz , Darougar Sepideh , Moghtaderi Mojgan , Ahmadiafshar Akefeh , Shakerian Behzad , Heidarzadeh Marzieh , Ghalebaghi Babak , Fathi Seyed Mohammad , Darabi Behzad , Fallahpour Morteza , Mohsenzadeh Azam , Ebrahimi Sarehsadat , Sharafian Samin , Vosughimotlagh Ahmad , Tafakoridelbari Mitra , Rahimi Haji‐Abadi Maziyar , Ashournia Parisa , Razaghian Anahita , Rezaei Arezou , Salami Fereshte , Shirmast Paniz , Bazargan Nasrin , Mamishi Setareh , Khazaei Hossein Ali , Negahdari Babak , Shokri Sima , Nabavizadeh Seyed Hesamedin , Bazregari Saeed , Ghasemi Ramin , Bayat Shiva , Eshaghi Hamid , Rezaei Nima , Abolhassani Hassan , Aghamohammadi Asghar 
Published: March 2021

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.