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

Abstract

Leukocyte adhesion de ciency type I is rare primary immunode ciency disorder characterized by mutations in the ITGB2 gene encoding CD18. We present clinical and immunological features of 15 patients with leukocyte adhesion de ciency type I (LAD-I). Targeted next-generation sequencing was performed with either a primary immunode ciency gene panel comprising 266 genes or a small LADpanel consisting of ve genes for genetic analysis. To measure the expression level of integrins on the leukocyte surface, ow cytometry analysis was performed. The median age of the patients at diagnosis was 3 (1-48) months. Eleven (73%) of the 15 patients had LAD-I diagnosis in their rst 6 months, and fourteen (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-I were characterized, of which two (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 HSCT. Two of them 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.

Rare and Heterogeneous manifestations of Leucocyte adhesion deficiency type 1: Report of two cases with diagnostic dilemmas and Novel ITGB mutation.

“…that were usually found pathogenic. Several novel mutations have also been reported earlier 6,11,[21][22][23] In a Chinese cohort of seven patients, novel mutations were identi ed in four 24 . Tipu et al 15 have reported genetic analysis of 12 Pakistani patients with ve pathogenic variants in eight of them and one of them was novel.…”

“…As a result, there are recurrent infections, especially bacterial and fungal infections of varying severity, non-healing wounds without pus formation, and early death usually in infancy 3,8 . There is often a history of delayed separation of the umbilical cord and omphalitis 3,8,[11][12][13] .…”

Identification of Hub Genes and Therapeutic Agents for IgA Nephropathy Through Bioinformatics Analysis and Experimental Validation

“…ITGB2 encodes the integrin beta chain, which combines with multiple different alpha chains to form different integrin heterodimers. It participates in cell surface-mediated signaling as well as immune response, and defects in this gene cause leukocyte adhesion deficiency ( 24 ). ITGB2 has also been reported to be negatively correlated with eGFR in patients with CKD ( 25 ) and involved in cell adhesion and extracellular matrix remodeling in renal cancer ( 26 ).…”

Deficiencia de adhesión leucocitaria: detección de los primeros casos en Paraguay

“…1,2 Dentro de los defectos de fagocitos se describe una enfermedad con incidencia aproximada de 1:100,000 nacidos vivos denominada deficiencia de adhesión leucocitaria (LAD, de "Leucocyte adhesion deficiency", por sus siglas en inglés), caracterizada por alteración en la migración de los leucocitos desde los vasos sanguíneos al sitio de inflamación, manifestándose clínicamente con retraso en la caída del cordón umbilical, onfalitis e infecciones bacterianas recurrentes de la piel y las mucosas, 3,4 además de leucocitosis persistente en la sangre periférica, debido a la incapacidad de los leucocitos para adherirse al endotelio vascular y migrar al tejido. 5,6 La deficiencia de adhesión leucocitaria se clasifica en tipo 1 (LAD-1), tipo 2 (LAD-2) y tipo 3 (LAD-3). La LAD-1 es un desorden autosómico recesivo provocado por mutaciones en el gen ITGβ2 que codifica para la cadena β (CD18) de las integrinas β2, esenciales para la adhesión de los leucocitos al endotelio vascular y la extravasación.…”

“…La mayor parte de los estudios asociados con deficiencia de adhesión leucocitaria provienen de países como India, Irán y Turquía, 5,6,11 y son escasos en Latinoamérica. [12][13][14] El primer caso en América del Sur fue reportado en 2012.…”