1. Autoimmune manifestations among 461 patients with monogenic inborn errors of immunity
- Author
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Soheila Alyasin, Hamid Ahanchian, Babak Ghalebaghi, Sarehsadat Ebrahimi, Sima Shokri, Hassan Abolhassani, Nasrin Bazargan, Alireza Shafiei, Arash Kalantari, Mahnaz Sadeghi-Shabestari, Marzieh Heidarzadeh, Ramin Ghasemi, Mitra Tafakoridelbari, Javad Tafaroji, Javad Mohammadi, Marzieh Tavakol, Shiva Bayat, Afshin Shirkani, Arezou Rezaei, Taher Cheraghi, Mansoureh Shariat, Asghar Aghamohammadi, Nasrin Behniafard, Mohammad Hossein Eslamian, Azam Mohsenzadeh, Mehrnaz Mesdaghi, Fereshte Salami, Zahra Chavoshzadeh, Maryam Khoshkhui, Tannaz Moeini Shad, Reza Yazdani, Babak Negahdari, Samin Sharafian, Morteza Fallahpour, Behzad Shakerian, Samaneh Delavari, Roya Sherkat, Behzad Darabi, Anahita Razaghian, Setareh Mamishi, Mohammad Nabavi, Seyed Alireza Mahdaviani, Seyed Hesamedin Nabavizadeh, Sepideh Darougar, Akefeh Ahmadiafshar, Rasoul Nasiri Kalmarzi, Mojgan Moghtaderi, Nima Rezaei, Farahzad Jabbari-Azad, Seyed Erfan Rasouli, Hossein Ali Khazaei, Salar Pashangzadeh, Gholamreza Hassanpour, Javad Ghaffari, Abbas Khalili, Hossein Esmaeilzadeh, Gholamreza Azizi, Rasol Molatefi, Seyed Mohammad Fathi, Paniz Shirmast, Mahnaz Jamee, Parisa Ashournia, Mohammad Hassan Bemanian, Ahmad Vosughimotlagh, Hamid Eshaghi, Maziyar Rahimi Haji-Abadi, Saeed Bazregari, Abbas Dabbaghzadeh, Saba Arshi, and Tooba Momen
- Subjects
Adult ,Male ,Adolescent ,Immunology ,Autoimmunity ,Disease ,Iran ,medicine.disease_cause ,Autoimmune Diseases ,LRBA ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Humans ,Immunology and Allergy ,Medicine ,030212 general & internal medicine ,Dysgammaglobulinemia ,Child ,Sinusitis ,Adaptor Proteins, Signal Transducing ,Retrospective Studies ,business.industry ,Autoimmune Cytopenia ,Common variable immunodeficiency ,High-Throughput Nucleotide Sequencing ,Immune dysregulation ,medicine.disease ,Common Variable Immunodeficiency ,030228 respiratory system ,Pediatrics, Perinatology and Child Health ,Female ,business - 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, immunological, 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), 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 (due to phenocopies of IEI genes) to discover responsible genes for the immune dysregulation at an early stage of the disease.
- Published
- 2021
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