D3.356 - Unconventional T cells in leukocyte adhesion deficiency I (LAD-I)

Leukocyte adhesion deficiency type 1 (LAD1) is a rare autosomal recessive immunodeficiency caused by mutations in the ITGB2 gene, leading to decreased or absent expression of CD18. This impairs mostly neutrophil function but can affect NK cells and cytotoxic T lymphocytes (CTLs) as well. The clinical phenotype of LAD1 is varied, with some patients exhibiting fluctuating expression of CD18, which is potentially linked to somatic reverse mutations.

We aimed to evaluate unconventional lymphocyte populations in a patient with LAD1, including invariant natural killer T (iNKT) and γδT cells, along with immune checkpoint molecules and activation markers. This study is the first to assess these parameters in LAD1.Flow cytometry was performed on isolated peripheral blood mononuclear cells (PBMCs). PBMCs were stained with monoclonal antibodies to assess the percentages of iNKT and γδT lymphocytes with their subpopulations, evaluate immune checkpoint markers and the activation status of γδT cell. Data analysis was conducted using Kaluza Analysis Software (Beckman Coulter). 

The percentage of iNKT cells in the patient was comparable to healthy individuals. However, the typical dominance of the Vδ2 subpopulation among γδT cells was absent, and most γδT cells displayed a terminally differentiated phenotype with reduced activation. The Vδ1 subpopulation exhibited overexpression of immune checkpoint molecules, suggesting impaired activation and proliferation, which was supported by decreased CD226 and NKG2D expression.

This study provides new insights into the immune profile of a LAD1 patient, emphasizing the absence of typical Vδ2 γδT cell dominance and impaired γδT cell activation.