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. 2021 Aug;32(6):1335-1348.
doi: 10.1111/pai.13510. Epub 2021 May 13.

Autoimmune manifestations among 461 patients with monogenic inborn errors of immunity

Gholamreza Azizi  1 , Marzieh Tavakol  1 , Reza Yazdani  2   3 , Samaneh Delavari  2 , Tannaz Moeini Shad  2 , Seyed Erfan Rasouli  1 , Mahnaz Jamee  1 , Salar Pashangzadeh  2 , Arash Kalantari  4 , Mansoureh Shariat  5 , Alireza Shafiei  6 , Javad Mohammadi  7 , Gholamreza Hassanpour  8 , Zahra Chavoshzadeh  9 , Seyed Alireza Mahdaviani  10 , Tooba Momen  11 , Nasrin Behniafard  12 , Mohammad Nabavi  13 , Mohammad Hassan Bemanian  13 , Saba Arshi  13 , Rasol Molatefi  14 , Roya Sherkat  15 , Afshin Shirkani  16 , Soheila Alyasin  17 , Farahzad Jabbari-Azad  18 , Javad Ghaffari  19 , Mehrnaz Mesdaghi  20 , Hamid Ahanchian  18 , Maryam Khoshkhui  18 , Mohammad Hossein Eslamian  21 , Taher Cheraghi  22 , Abbas Dabbaghzadeh  23 , Rasoul Nasiri Kalmarzi  24 , Hossein Esmaeilzadeh  17 , Javad Tafaroji  25 , Abbas Khalili  26 , Mahnaz Sadeghi-Shabestari  27 , Sepideh Darougar  9 , Mojgan Moghtaderi  17 , Akefeh Ahmadiafshar  28 , Behzad Shakerian  29 , Marzieh Heidarzadeh  30 , Babak Ghalebaghi  22 , Seyed Mohammad Fathi  31 , Behzad Darabi  32 , Morteza Fallahpour  13 , Azam Mohsenzadeh  33 , Sarehsadat Ebrahimi  34 , Samin Sharafian  9 , Ahmad Vosughimotlagh  35 , Mitra Tafakoridelbari  34 , Maziyar Rahimi Haji-Abadi  34 , Parisa Ashournia  34 , Anahita Razaghian  34 , Arezou Rezaei  2 , Fereshte Salami  2 , Paniz Shirmast  3 , Nasrin Bazargan  36 , Setareh Mamishi  37 , Hossein Ali Khazaei  38 , Babak Negahdari  39 , Sima Shokri  13 , Seyed Hesamedin Nabavizadeh  17 , Saeed Bazregari  40 , Ramin Ghasemi  29 , Shiva Bayat  41 , Hamid Eshaghi  36 , Nima Rezaei  2 , Hassan Abolhassani  2   42 , Asghar Aghamohammadi  2   3
Affiliations

Autoimmune manifestations among 461 patients with monogenic inborn errors of immunity

Gholamreza Azizi et al. Pediatr Allergy Immunol. 2021 Aug.

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.

Keywords: autoimmunity; inborn errors of immunity; inflammation; primary immunodeficiencies.

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