Leucocyte adhesion deficiency and related disorders

Disorders of leukocyte motility present clinically with recurrent infections of the skin and mucosa. These infections are accompanied by inflammatory symptoms that can complicate the clinical course of the disease. The clinical phenotype reflects impaired migration of neutrophils and other leukocytes from the bloodstream to sites of inflamed tissue, leaving infections poorly contained at the level of innate host defence.

Phenotypic severity varies across the spectrum, and a syndromic-versus-nonsyndromic distinction is not informative for this group of primary immunodeficiencies, which are characterised by their immunological phenotype rather than by additional systemic features.

Due to insufficient data, no reliable statement on prevalence can currently be made.

A large number of genes have been associated with disorders of leukocyte motility. The genetic forms can be grouped into integrin beta-2 (CD18) defects and other adhesion-cascade defects, including leukocyte adhesion deficiency type I (ITGB2; absent or dysfunctional LFA-1 (CD11a/CD18) on all leukocytes) and leukocyte adhesion deficiency types II to IV (additional primary-immunodeficiency syndromes affecting the adhesion cascade).

The genetic conditions associated with disorders of leukocyte motility predominantly follow autosomal recessive inheritance, as documented in the current overview literature. In a large single-centre cohort of inborn errors of immunity, the majority of patients with a confirmed molecular diagnosis carried biallelic variants in autosomal recessive disorders. Less common alternative inheritance patterns are described for individual entities.

• Where disorders of leukocyte motility are suspected to have a genetic cause, molecular genetic testing can identify the underlying condition and confirm a clinical suspicion.
• The identified entity guides further clinical management and is a prerequisite for targeted medical care; therapeutic options are evaluated individually by the treating physicians.
• Identification of the underlying pathogenic germline variant enables predictive testing of at-risk family members and provides information relevant to family planning.

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• Fekadu J, Modlich U, Bader P, Bakhtiar S. Understanding the role of LFA-1 in leukocyte adhesion deficiency type I (LAD I): moving towards inflammation? Int J Mol Sci. 2022;23(7):3578. doi:10.3390/ijms23073578. PMID:; PMCID: PMC8998723