- D1.344 - Hidden Immunodeficiency in Adult Bronchiectasis: Lymphocyte Subsets, Humoral Defects, and Genetic Findings

Bronchiectasis is a chronic lung disease with a heterogeneous etiology, commonly resulting from recurrent lower respiratory tract infections and persistent inflammation. Primary and secondary immunodeficiencies represent important but frequently overlooked causes of bronchiectasis, particularly in patients with early disease onset, multilobar involvement, and progressive disease course. While advances in immunological diagnostics have enabled deeper immune phenotyping, data focusing on lymphocyte subsets and genetic findings in adult bronchiectasis remain limited. This study aimed to comprehensively characterize immunological abnormalities and genetic findings in adult patients with immunodeficiency-associated bronchiectasis.

Twenty-one adult patients with a diagnosis of immunodeficiency and bronchiectasis detected on thoracic computed tomography (CT), followed at the Immunology and Allergy Clinics of Süreyyapaşa Chest Diseases and Thoracic Surgery Training and Research Hospital, were retrospectively evaluated. Clinical, laboratory, immunological, and radiological data were reviewed. Humoral immunity parameters, lymphocyte flow cytometry including T-, B-, and NK-cell subsets, and B-cell subpopulations were analyzed and compared with age-adjusted reference ranges. Genetic analysis was performed in selected patients based on clinical and immunological phenotypes.

All patients had a history of recurrent infections. Hypogammaglobulinemia was highly prevalent (IgG 85.7%, IgA 95.2%, IgM 71.4%), with marked IgG subclass deficiencies, particularly IgG2 (76.2%) and IgG4 (52.4%). Functional antibody responses were absent in more than half of the evaluable patients. Lymphocyte subset analysis revealed reduced CD4⁺ T cells in 28.6%, CD19⁺ B cells in 33.3%, and NK cells in 38.1% of patients, while class-switched memory B-cell deficiency was observed in 33.3%. Cylindrical bronchiectasis was the predominant radiological pattern.

Pathogenic or likely pathogenic variants related to primary immunodeficiency were identified in three patients. A heterozygous TNFRSF13B frameshift variant was associated with combined hypogammaglobulinemia and T-cell lymphopenia, whereas a homozygous TNFRSF9 deletion with a PARK7 variant of uncertain significance showed hypogammaglobulinemia, reduced switched memory B cells, and NK-cell deficiency. A heterozygous PLCG2 variant of uncertain significance was linked to severe B-cell deficiency and lymphopenia. Overall, genetic findings were associated with more pronounced immunophenotypic abnormalities and more extensive bronchiectasis.

Adult patients with bronchiectasis frequently harbor underlying immunodeficiency accompanied by delayed diagnosis and complex immunological abnormalities. Beyond serum immunoglobulin levels, comprehensive evaluation including lymphocyte subset analysis, functional antibody responses, and targeted genetic testing is essential for accurate diagnosis and optimized management. Early recognition of immunodeficiency in bronchiectasis may prevent disease progression and irreversible lung damage.