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Clinical Trial
. 2021 Oct;206(1):47-55.
doi: 10.1111/cei.13645. Epub 2021 Aug 5.

Clinical and laboratory findings in patients with leukocyte adhesion deficiency type I: A multicenter study in Turkey

Ismail Yaz  1 , Begum Ozbek  1 , Hacer Neslihan Bildik  1 , Cagman Tan  1 , Sevil Oskay Halacli  1 , Elif Soyak Aytekin  1 , Saliha Esenboga  1 , Sukru Cekic  2 , Sara Sebnem Kilic  2 , Ozlem Keskin  3 , Karin van Leeuwen  4 , Dirk Roos  4 , Deniz Cagdas  1 , Ilhan Tezcan  1
Affiliations
Clinical Trial

Clinical and laboratory findings in patients with leukocyte adhesion deficiency type I: A multicenter study in Turkey

Ismail Yaz et al. Clin Exp Immunol. 2021 Oct.

Abstract

Leukocyte adhesion deficiency type I is a rare primary immunodeficiency disorder characterized by mutations in the ITGB2 gene encoding CD18. We present clinical and immunological features of 15 patients with leukocyte adhesion deficiency type 1 (LAD-1). Targeted next-generation sequencing was performed with either a primary immunodeficiency gene panel comprising 266 genes or a small LAD-panel consisting of five genes for genetic analysis. To measure the expression level of integrins on the leukocyte surface, flow cytometry analysis was performed. The median age of the patients at diagnosis was 3 (1-48) months. Eleven (73%) of the 15 patients had a LAD-1 diagnosis in their first 6 months and 14 (93%) patients had consanguineous parents. Delayed separation of the umbilical cord was present in 80% (n = 12) of the patients in our cohort, whereas omphalitis was observed in 53% (n = 8) of the patients. Leukocytosis with neutrophil predominance was observed in 73% (n = 11) patients. Nine distinct variants in the ITGB2 gene in 13 of the 15 patients with LAD-1 were characterized, two of which (c.305_306delAA and c.779_786dup) are novel homozygous mutations of ITGB2. Four unrelated patients from Syria had a novel c.305_306delAA mutation that might be a founder effect for patients of Syrian origin. Four (27%) patients underwent hematopoietic stem cell transplantation. Two patients died because of HSCT complications and the other two are alive and well. Early differential diagnosis of the patients is critical in the management of the disease and genetic evaluation provides a basis for family studies and genetic counseling.

Keywords: CD18; HSCT; ITGB2; integrin; leukocyte adhesion deficiency type 1 (LAD-1).

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Conflict of interest statement

The authors declare that they have no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Clinical findings in patients with leukocyte adhesion deficiency type 1 (LAD‐1). *Some patients have more than one clinical finding. The total number is not the number of patients
FIGURE 2
FIGURE 2
Percentage of patients according to absolute numbers of lymphocyte subgroups compared to age‐related reference values
FIGURE 3
FIGURE 3
cDNA of ITGB2 gene and positions of mutations. *The figure was drawn according to NCBI Reference Sequence: NM_000211.5
FIGURE 4
FIGURE 4
Domain structure of the CD18 protein encoded by ITGB2 and positions of mutations. CD, cytoplasmic domain; CYS, cysteine‐rich tandem repeat; TD, transmembrane domain; VWFA, von Willebrand factor type A domain
See this image and copyright information in PMC

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