International clinical consensus on leukocyte adhesion deficiency-I: Modified Delphi analysis

Leukocyte adhesion deficiency-I (LAD-I) is a rare autosomal-recessive inborn error of immunity caused by mutations in ITGB2, encoding CD18, which is essential for leukocyte endothelial adhesion and tissue migration. LAD-I is predominantly characterized by frequent life-threatening infections and hyperinflammatory complications, with high rates of pediatric mortality and morbidity without allogeneic hematopoietic stem cell transplantation. Historically, diagnosis and severity classification were based on polymorphonuclear leukocyte CD18 expression. Given improved knowledge of prognostic factors and an evolving treatment landscape, contemporary guidance for severity classification and management is needed.

We sought to provide international, expert-led consensus recommendations for the diagnosis and severity classification of LAD-I; and to characterize standard of care and burden of illness for patients with severe LAD-I.

Twelve geographically diverse experts (3 steering committee members and 9 Delphi participants) were recruited to participate in a modified Delphi study. Two rounds of online questionnaires were conducted, plus a virtual workshop. Final recommendations were approved by all experts.

Consensus was achieved across 26 recommendations regarding the diagnosis and treatment of patients with LAD-I. Experts agreed LAD-I severity classification should consider laboratory assessment in addition to clinical phenotype within a comprehensive framework. In the absence of symptoms, particularly in infancy, diagnosis and severity classification is based on flow cytometric assessments (CD18 and CD11a/CD11b expression) and molecular genetic testing or family history.

The framework developed by the Delphi panel will aid clinicians in the diagnosis, classification, and treatment of patients with LAD-I. Recommendations support best clinical practice that can lead to improved clinical outcomes.