Immunodeficiency BD-1 (Leukocyte Adhesion Deficiency Type 1)

By SWA

Overview:

BD-1 stands for Leukocyte Adhesion Deficiency Type 1 (LAD-1), a rare, inherited immunodeficiency disorder. It is characterized by the inability of certain white blood cells (leukocytes) to adhere properly to blood vessel walls, a crucial step required for them to exit the bloodstream and migrate to sites of infection or inflammation. As a result, the immune system cannot effectively fight off infections.

Causes and Genetics

LAD-1 is caused by mutations in the ITGB2 gene, which encodes the CD18 protein — a subunit of integrin molecules on the surface of white blood cells. Integrins are essential for leukocyte adhesion and migration. Without functional CD18, white blood cells cannot attach to the endothelium (the inner lining of blood vessels) and are unable to reach infected or inflamed tissues.

  • CD18 deficiency refers to a lack or dysfunction of this protein.

  • The disorder is inherited in an autosomal recessive pattern, meaning a child must inherit one defective copy of the ITGB2 gene from each parent to be affected.

Symptoms

Symptoms usually begin in infancy or early childhood and may include:

  • Frequent and severe bacterial infections, such as:

    • Recurrent skin abscesses (without pus formation)

    • Respiratory tract infections (e.g., pneumonia, sinusitis)

    • Gingivitis and periodontitis (severe gum infections)

    • Delayed separation of the umbilical cord (>3 weeks after birth)

    • Poor wound healing

  • Fever, fatigue, and other signs of systemic inflammation may also be present.

Diagnosis

Diagnosis typically involves a combination of laboratory tests and genetic analysis:

  • Complete blood count (CBC) with differential: Often shows elevated white blood cell count (leukocytosis), especially neutrophils.

  • Quantitative measurement of immunoglobulins (IgG, IgM, IgA, and sometimes IgE) to assess overall immune function.

  • C-reactive protein (CRP) and other inflammatory markers to evaluate ongoing infection or inflammation.

  • Microbiological cultures to identify pathogenic organisms, especially in the lungs, skin, or oral cavity.

  • Chest X-ray or other imaging: Used if respiratory infections are suspected to assess for pneumonia or abscesses.

  • Flow cytometry: To measure the expression of CD18 and related integrins on white blood cells.

  • Genetic testing: Confirms mutations in the ITGB2 gene, providing a definitive diagnosis.

Treatment

Management of LAD-1 focuses on preventing and treating infections, and in severe cases, restoring immune function:

  1. Antimicrobial prophylaxis:

    • Long-term use of antibiotics or antifungals to prevent infections.

  2. Immunoglobulin therapy (IVIG or SCIG):

    • Provides passive immunity and may help support the immune response.

  3. Hematopoietic stem cell transplantation (HSCT):

    • The only curative option for severe LAD-1.

    • Involves replacing the patient’s defective bone marrow with healthy donor stem cells.

    • Success depends on the timing of the transplant and availability of a compatible donor.

  4. Supportive care:

    • Good oral hygiene and prompt treatment of infections are critical.

    • Wound care and monitoring for signs of systemic infection.

Prognosis

The prognosis of LAD-1 varies depending on the severity of the CD18 deficiency:

  • Mild to moderate cases: With early diagnosis and consistent treatment, many patients can lead relatively normal lives.

  • Severe cases: Without stem cell transplantation, life-threatening infections may occur in early childhood, often leading to early mortality.

  • Long-term outcomes improve significantly with early intervention and effective infection management.

Additional Information

  • Prevalence: LAD-1 is extremely rare, with only a few hundred documented cases worldwide.

  • Inheritance: As an autosomal recessive condition, both parents must be carriers of the ITGB2 mutation. Genetic counseling is recommended for affected families.

  • Research: Gene therapy and novel immune-modulating treatments are currently being explored as potential future therapies.

     

© 2000-2025 Sieglinde W. Alexander. All writings by Sieglinde W. Alexander have a five-year copyright. Library of Congress Card Number: LCN 00-192742 ISBN: 0-9703195-0-9

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