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Immunology: type 1 feline leukocyte adhesion deficiency (FLAD I)

ffelis

Synonym(s): LAD


Introduction

  • Type I Leukocyte Adhesion Deficiency in domestic cats (FLAD I) was first described in 2017. It is an autosomal recessive, primary immunodeficiency disease, homologous to that recognized in people, cattle and dogs (usually Irish Setters).
  • Cause: a neutrophil membrane glycoprotein called leukocyte integrin beta-2 subunit (ITGB2 or CD18) is deficient because of a 24 base pair deletion mutation.
  • This is a different mutation from that found in dogs, but in the same gene. It causes failure of neutrophils to adhere to the linings of blood vessels, so they cannot exit as normal into tissues.
  • Extreme neutrophilia because of continued bone marrow production with impaired neutrophil chemotaxis out of blood vessels and into inflamed tissues.
  • Signs: increased susceptibility to infections, especially bacterial. Signs are reportedly milder than those seen in puppies, potentially allowing survival into adulthood with diligent veterinary care and appropriate antimicrobial therapy.
  • Prognosis: guarded. Survival into adulthood can be anticipated but considerable veterinary care, including long-term antimicrobial therapy, will very likely be needed.

Pathogenesis

Etiology

  • A neutrophil membrane glycoprotein called leukocyte integrin beta-2 subunit (ITGB2 or CD18) is deficient because of a deletion mutation. Neutrophils therefore fail to express cell surface integrins. This causes failure of neutrophils to adhere properly to the linings of blood vessels, so they do not exit into tissues, where they are needed to combat infections and help manage inflammation.
  • In a reported case, a 24 base pair deletion was found at the exon 2 to intron 2 boundary, predicted to cause premature termination of mRNA translation and truncated protein synthesis.
  • CD18 is also involved in T-lymphocyte proliferation. Clinical episodes in an affected cat were reported to be milder than would be typical in an affected puppy. This was considered potentially due to an alternative, CD18-independent, T-cell proliferation pathway.

Diagnosis

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Treatment

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Prevention

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Outcomes

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Further Reading

Publications

Refereed Papers

  • Recent references from PubMed and VetMedResource.
  • Bauer T R, Pratt S M, Palena C M, Raj K & Giger U (2017) Feline leukocyte adhesion (CD18) deficiency caused by a deletion in the integrin β2 (ITGB2) gene. Vet Clin Pathol 46 (3), 391-400 PubMed.

 

Organisation(s)

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