Monogenic Primary Immunodeficiency Disorder Associated with Common Variable Immunodeficiency and Autoimmunity

Abstract

Background: 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. Methods: 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. Results: In the 27 studied patients, 11 different genetic defects were identified, and the most common mutated gene was LRBA, 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 (n = 9, 90.0%) primarily developed infectious complications, while in patients with poly-autoimmunity, the most common first presentation was enteropathy (n = 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. Conclusion: 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.

Primary antibody deficiencies in Turkey: molecular and clinical aspects

“…In addition to recurrent infections in CVID, additional clinical symptoms like gastrointestinal disorders, allergy, lymphadenopathy, and/or autoimmune diseases. Autoimmunity is a common event and presents in 20-30% of CVID patients [9]. Clinical and genetic phenotypes of CVID are heterogeneous [10,11].…”

Autoimmune manifestations among 461 patients with monogenic inborn errors of immunity

“…Among patients with autoimmunity, hematologic (42.2%), rheumatologic (26.7%), gastrointestinal (27.2%), dermatologic (16.7%), neurologic (7.8%), and endocrine (7.8%) affected organs by autoimmune diseases were documented. Moreover, in patients with monogenic IEIs, immune thrombocytopenic purpura (ITP) (6.5%), juvenile idiopathic arthritis (JIA) (4.8%), and autoimmune TA B L E 1 Demographic data in patients with monogenic inborn errors of immunity 11 (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) 13 (8-21.5) 11 (5.7-20) .030 * 11 (6.5-21.5) 14.5 (10.2-21.5) .307…”

Specific Immune Response and Cytokine Production in CD70 Deficiency

“…Moreover, overexpression of CD27 and its soluble form and surprisingly also a higher expression of CD70 have been documented in several types of autoimmune disorders including systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, and psoriasis (64,65). Thus, additional mechanisms may explain the phenotype of our patient, and dysregulation of the CD27-CD70 pathway can contribute to various forms of inflammatory and autoimmune disorders, although additional investigations are required to fully understand the mechanisms involved (66).…”