Background Leukocyte adhesion deficiency (LAD) or CD18 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 CD18 on neutrophils. In vitro functional assays assessed CD18-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 beta-2 subunit (ITGB2) 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 CD18 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 CD18-independent T-cell response at higher doses. Molecular genetic analysis of the ITGB2 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, CD18-independent T-cell-proliferation pathway.

3779 Leukocyte adhesion deficiency (LAD) caused by CD18 deficiency is an autosomal recessive immunodeficiency which has been described in humans, Irish Setter dogs, Holstein cattle, and transgenic mice. We report here on the characterization of the clinical features and leukocyte function abnormalities of a novel feline model of leukocyte adhesion deficiency. The proband was a 5 year old male domestic longhair cat with a life-long history of infections, inflammation and granulomas. Severe gingivitis was recognized at 8 weeks of age which progressed to peridontitis and loss of all deciduous and adult teeth before 1 year of age. Over the next years this cat experienced recurrent severe upper respiratory infections, gastroenteritis, anterior uveitis, various abscesses, and epidermal sloughing with sepsis secondary to small grooming lacerations. The various illnesses seemed to be responsive to various long-term antibiotic as well as glucocorticoid treatments. Complete blood cell counts revealed a persistent severe leukocytosis (50-91,000/μl) due to mature neutrophilia with few toxic changes, and mild lymphocytosis, monocytosis and eosinophilia. Serum immunoglobulin concentrations were normal. Compared to feline control cells, neutrophils of the proband did not express any CD18 on the cell surface as determined with two monoclonal anti-CD18 antibodies but normal CD45 expression. Adhesion of affected neutrophils with and without PMA activation was severally impaired; the adhesion of normal feline neutrophils could be completely blocked by the anti-CD18 antibody. In a proliferation assay the proband's T-cells responded weakly at 1 pg SEA but near normally at 100 pg SEA, suggesting a CD18-independent T-cell response in cats. Sequencing of the feline CD18 β-integrin gene is being completed. In conclusion, this naturally-occurring feline model of CD18 deficiency exhibits similar features to LAD in other species. However, feline LAD seems clinically milder allowing for a longer life expectancy possibly due to T-cell independent activities. This LAD model may be helpful in developing and assessing novel therapies. Disclosures: No relevant conflicts of interest to declare.