Analysis of Clinical, Immunological and Molecular Features of Leukocyte Adhesion Deficiency Type I in Egyptian Children

J Clin Immunol. 2024 Apr 5;44(4):92. doi: 10.1007/s10875-024-01693-x.

Abstract

Purpose: Leukocyte adhesion deficiency (LAD) represents a rare group of inherited inborn errors of immunity (IEI) characterized by bacterial infections, delayed umbilical stump separation, and autoimmunity. This single-center study aimed at describing the clinical, immunological, and molecular characterizations of 34 LAD-I Egyptian pediatric patients.

Methods: Details of 34 patients' personal medical history, clinical and laboratory findings were recorded; Genetic material from 28 patients was studied. Mutational analysis was done by Sanger sequencing.

Results: Omphalitis, skin and soft tissue infections with poorly healing ulcers, delayed falling of the umbilical stump, and recurrent or un-resolving pneumonia were the most common presentations, followed by chronic otitis media, enteropathy, periodontitis; and recurrent oral thrush. Persistent leukocytosis and neutrophilia were reported in all patients, as well as CD18 and CD11b deficiency. CD18 expression was < 2% in around 90% of patients. Sixteen different pathological gene variants were detected in 28 patients who underwent ITGß2 gene sequencing, of those, ten were novel and six were previously reported. Three families received a prenatal diagnosis. Patients were on antimicrobials according to culture's results whenever available, and on prophylactic Trimethoprim-Sulfamethoxazole 5 mg/kg once daily, with regular clinical follow up. Hematopoietic stem cell transplantation (HSCT) was offered for 4 patients. However due to severity of the disease and delay in diagnosis, 58% of the patients passed away in the first 2 years of life.

Conclusion: This study highlights the importance of early diagnosis and distribution of ITGß2 gene mutation in Egyptian children. Further molecular studies, however, remain a challenging necessity for better disease characterization in the region.

Keywords: Genetic diagnosis; Inborn error of immunity; Leukocyte adhesion deficiency; Phagocytic defect.

MeSH terms

  • CD18 Antigens* / genetics
  • CD18 Antigens* / metabolism
  • Child
  • Egypt / epidemiology
  • Humans
  • Leukocyte-Adhesion Deficiency Syndrome* / diagnosis
  • Leukocyte-Adhesion Deficiency Syndrome* / genetics
  • Leukocyte-Adhesion Deficiency Syndrome* / therapy
  • Leukocytes / metabolism

Substances

  • CD18 Antigens

Supplementary concepts

  • Leukocyte adhesion deficiency type 1