Monogenic Primary Immunodeficiency Disorder Associated with Common Variable Immunodeficiency and Autoimmunity
Authors: Asgardoon Mohammad Hossein , Azizi Gholamreza , Yazdani Reza , Sohani Mahsa , Pashangzadeh Salar , Kalantari Arash , Shariat Mansoureh , Shafiei Alireza , Salami Fereshte , Jamee Mahnaz , Rasouli Seyed Erfan , Mohammadi Javad , Hassanpour Gholamreza , Tavakol Marziyeh , 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 , Delavari Samaneh , Shirmast Paniz , Babaha Fateme , Samavat Ashraf , Mamishi Setareh , Khazaei Hossein Ali , Negahdari Babak , Rezaei Nima , Abolhassani Hassan , Aghamohammadi Asghar 
Published: July 2020

<b><i>Background:</i></b> Common variable immunodeficiency (CVID) is the most frequent primary immunodeficiency disorder mainly characterized by recurrent bacterial infections besides other immunological defects including loss of or dysfunction of B cells and decreased immunoglobulin levels. In this study, our aim is to evaluate clinical, immunological, and molecular data of patients with a primary clinical diagnosis of CVID and autoimmune phenotype with a confirmed genetic diagnosis. <b><i>Methods:</i></b> Among 297 patients with CVID, who were registered in the Iranian Primary Immunodeficiency Registry at Children’s Medical Center Hospital in Iran, 83 patients have been genetically examined and 27 patients with autoimmunity and confirmed genetic mutations were selected for analysis. Whole-exome sequencing and confirmatory Sanger sequencing methods were used for the study population. A questionnaire was retrospectively filled for all patients to evaluate demographic, laboratory, clinical, and genetic data. <b><i>Results:</i></b> In the 27 studied patients, 11 different genetic defects were identified, and the most common mutated gene was <i>LRBA</i>, reported in 17 (63.0%) patients. Two patients (7.7%) showed autoimmune complications as the first presentation of immunodeficiency. Eleven patients (40.7%) developed one type of autoimmunity, and 16 patients (59.3%) progressed to poly-autoimmunity. Most of the patients with mono-autoimmunity (<i>n</i> = 9, 90.0%) primarily developed infectious complications, while in patients with poly-autoimmunity, the most common first presentation was enteropathy (<i>n</i> = 6, 37.6%). In 13 patients (61.9%), the diagnosis of autoimmune disorders preceded the diagnosis of primary immunodeficiency. The most frequent autoimmune manifestations were hematologic (40.7%), gastrointestinal (48.1%), rheumatologic (25.9%), and dermatologic (22.2%) disorders. Patients with poly-autoimmunity had lower regulatory T cells than patients with mono-autoimmunity. <b><i>Conclusion:</i></b> In our cohort, the diagnosis of autoimmune disorders preceded the diagnosis of primary immunodeficiency in most patients. This association highlights the fact that patients referring with autoimmune manifestations should be evaluated for humoral immunity.