Publication details

Clinical and Molecular Characteristics of X-Linked Agammaglobulinemia Patients 55 Years or Older

Authors	CHIN Aaron T OCHS Hans D KOBAYASHI Roger ABOLHASSANI Hassan ALACHKAR Hana BARMETTLER Sara BAXENDALE Helen BOILING Kristina CATANZARO Jason CHUA Ignastius COULTER Tanya CUNNINGHAM-RUNDLES Charlotte ELCOMBE Suzanne E FISCHER Alain GRIMBACHER Bodo GUPTA Sudhir HERRIOT Richard HERWADKAR Archana IMAI Kohsuke INOUE Shota KIRKPATRICK Charles KNUTSEN Alan P KUMARARATNE Dinakantha LEA Edward MING-WEI Lin LITZMAN Jiří MAHLAOUI Nizar MORIYA Kunihiko NONOYAMA Shigeaki PATEL Smita PEREZ Elena QUINTI Isabella HOSTOFFER Robert W ROTHENFUSSER Simon SARGUR Ravishankar SHIELDS Adrian SOGKAS Georgios SUAN Dan TAN Tyng THOMAS Moira WARNATZ Klaus YOUNGER Elizabeth M KUO Caroline Y
Year of publication	2025
Type	Article in Periodical
Magazine / Source	Journal of Allergy and Clinical Immunology
MU Faculty or unit	Faculty of Medicine
Citation
web	https://www.jaci-inpractice.org/article/S2213-2198(25)00606-3/abstract
Doi	https://doi.org/10.1016/j.jaip.2025.06.025
Keywords	Agammaglobulinemia; Antibody deficiency; Bruton tyrosine kinase (BTK); Inborn error of immunity (IEI); X-linked agammaglobulinemia (XLA)
Description	Background: X-linked agammaglobulinemia (XLA), caused by mutations in the Bruton tyrosine kinase (BTK) gene, leads to defective B-cell development and low or absent serum immunoglobulins. Advances in diagnosis and treatment have improved outcomes, allowing some patients to live beyond their sixth decade. Objective: To describe the clinical, genetic, treatment, and functional status of XLA patients aged 55 years or older. Methods: Immunologists provided anonymized, physician-reported clinical and molecular details of XLA patients aged 55 years or older. Patients were categorized as having missense mutations (BTK missense) or non-missense mutations (BTK non-missense). Results: Fifty-seven patients were submitted. Forty-eight were considered for final analysis, including 43 with molecularly confirmed XLA and 5 with a strong clinical history. Persistent respiratory infections were common: 64.6% (upper respiratory tract) and 83.3% (lower respiratory tract). Chronic lung disease (72.9%) and gastrointestinal/hepatic disorders (47.9%) were among the most prevalent complications. Most living patients (80.5%) reported good functional status (Karnofsky scores > 80). Missense variants accounted for 62.8% (n = 27), non-missense variants for 37.2% (n = 16); 5 patients lacked classifiable mutation details. Among 34 patients with BTK expression data, 70.6% had detectable BTK protein, significantly more common in the missense group (83.3% vs 30%; P = .005). The non-missense group had higher mortality, more infections, greater antibiotic use, worse pulmonary function, and lower functional status. Conclusions: Chronic respiratory complications are common in older XLA patients, although most maintain good functional status. Genetic testing aids prognostication; BTK missense mutations are linked to better outcomes. Further research is needed to address the unique challenges of aging in XLA.