Survival and Clinical Outcomes of XLA Patients 55 years or older

Abstract

BACKGROUND: X-linked Agammaglobulinemia (XLA) is caused by mutations in the Bruton tyrosine kinase (BTK) gene, resulting in the absence of B cells and agammaglobulinemia. The introduction of antibiotics and replacement immunoglobulin G has improved life expectancy, but long-term comorbidities persist and remain poorly understood. OBJECTIVES: The study aims to characterize the demographic, clinical, functional, and molecular profiles of XLA patients who have survived beyond 55 years. METHODS: A survey conducted among twelve immunologists identified XLA patients aged 55 or older. Data on demographics, clinical history, genetic diagnosis, treatment, and comorbidities were collected. RESULTS: The survey identified 23 patients with XLA who lived beyond 55 years (range 55 to 74 years, median 65 years). Three patients died at an average age of 58.3 years and 21 out of 23 patients were white/Caucasian. Gene mutations were confirmed in 18 patients; of these, 6 had undetectable BTK levels while 8 had reduced or normal BTK expression. A family history of XLA was reported in 18 patients. Diagnosis was established at a median age of 6.5 years, and at 5 years in patients with known family history of XLA. Patients began receiving immunoglobulin therapy at a median age of 7.5 years, continuing for an average duration of 50.6 years. Common infections included upper respiratory infections (69.6%), pneumonia (60.9%), and sepsis (17.4%). The most frequent chronic comorbidities were bronchiectasis (60.9%), cardiovascular disease (43.5%), and malignancy (21.7%). Among the 20 living patients, eight were either fully or partially working. Most living patients (17/20) maintained a good quality of life defined as an ability to complete most independent activities of daily living (Kanofsky performance score?>80). The immunologists caring for these patients attributed the long-term survival primarily to consistent immunoglobulin replacement (56%) and secondarily to hypomorphic mutations (27.3%). CONCLUSIONS: This study is the first to report clinical, immunologic, and genetic characteristics of older patients with XLA. Compared to earlier studies, these patients experienced similar rates of respiratory infections and bronchiectasis but higher rates of malignancy. Despite significant comorbidities, most patients experienced quality of life consistent with independent living, primarily attributed to consistent immunoglobulin therapy.