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Feline leukocyte adhesion ( CD 18) deficiency caused by a deletion in the integrin β 2 ( ITGB 2 ) gene
Author(s) -
Bauer Thomas R.,
Pratt Suzanne M.,
Palena Christina M.,
Raj Karthik,
Giger Urs
Publication year - 2017
Publication title -
veterinary clinical pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.537
H-Index - 51
eISSN - 1939-165X
pISSN - 0275-6382
DOI - 10.1111/vcp.12526
Subject(s) - leukocyte adhesion deficiency , immunology , biology , exon , microbiology and biotechnology , neutrophilia , leukocytosis , cd18 , gene , genetics , flow cytometry , integrin alpha m
Background Leukocyte adhesion deficiency ( LAD ) or CD 18 deficiency is an autosomal recessive immunodeficiency which has been described in people, cattle, dogs, and knockout mice. Objectives The study goals were to characterize the clinicopathologic, immunologic, and molecular genetic features of feline LAD ( FLAD ) in a neutered male adult Domestic Longhair cat with severe leukocytosis and recurrent infections. Methods Flow cytometry evaluated surface expression of CD 18 on neutrophils. In vitro functional assays assessed CD 18‐dependent neutrophil adhesion and T‐cell proliferation. Genomic DNA and cDNA were used to identify a causative mutation in the coding sequence of the integrin β 2 subunit ( ITGB 2 ) gene. Results The affected cat developed periodontitis during the first months of life followed by recurrent infections poorly responsive to antibiotic therapy, accompanied by extreme neutrophilia. Neutrophils from the proband, compared to feline controls, did not express any CD 18 on the cell surface. Adhesion of affected neutrophils was severely impaired with and without phorbol‐myristate‐acetate activation. The proband's T‐cells proliferated weakly to 1 pg but normally to 100 pg staphylococcal enterotoxin A, suggesting a CD 18‐independent T‐cell response at higher doses. Molecular genetic analysis of the ITGB 2 gene revealed a 24 bp deletion at the exon 2 to intron 2 boundary (c.46_58 + 11del), predicting premature translational termination due to abnormal splicing of exon 1 to exon 3 or 4. Conclusions Feline LAD exhibits features similar to LAD in other species. However, clinical episodes in FLAD appeared milder allowing for an extended life expectancy under long‐term antimicrobial therapy, possibly due to an alternative, CD 18‐independent T‐cell proliferation pathway.