Monogenic Primary Immunodeficiency Disorder Associated with Common Variable Immunodeficiency and Autoimmunity.

Area of Science:

• Immunology
• Genetics
• Clinical Medicine

Background:

• Common variable immunodeficiency (CVID) is a primary immunodeficiency disorder characterized by recurrent infections, B cell defects, and low immunoglobulin levels.
• Autoimmunity is a significant clinical feature in some CVID patients, complicating diagnosis and management.

Purpose of the Study:

• To evaluate the clinical, immunological, and molecular data of CVID patients with an autoimmune phenotype and confirmed genetic diagnoses.
• To investigate the relationship between genetic defects, autoimmune manifestations, and disease progression in CVID.

Main Methods:

• Retrospective analysis of 27 CVID patients with autoimmunity from the Iranian Primary Immunodeficiency Registry.
• Whole-exome and Sanger sequencing for genetic mutation identification.
• Questionnaire-based data collection on demographic, laboratory, clinical, and genetic factors.

Main Results:

• Eleven distinct genetic defects were identified in 27 patients, with LRBA mutations being the most common (63.0%).
• Autoimmune complications preceded immunodeficiency diagnosis in 61.9% of patients; poly-autoimmunity was more common (59.3%) and associated with enteropathy as the first presentation.
• Hematologic, gastrointestinal, rheumatologic, and dermatologic disorders were the most frequent autoimmune manifestations; poly-autoimmunity patients had lower regulatory T cells.

Conclusions:

• Autoimmune disorders frequently precede the diagnosis of primary immunodeficiency in CVID patients.
• Patients presenting with autoimmune manifestations require thorough evaluation for underlying humoral immunodeficiency.