{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T16:20:39Z","timestamp":1759335639083,"version":"3.41.0"},"reference-count":38,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2017,7,27]],"date-time":"2017-07-27T00:00:00Z","timestamp":1501113600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["1ZIASC010384"],"award-info":[{"award-number":["1ZIASC010384"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["5P40\u2010OD010939"],"award-info":[{"award-number":["5P40\u2010OD010939"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Veterinary Clinical Pathol"],"published-print":{"date-parts":[[2017,9]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Leukocyte adhesion deficiency (<jats:styled-content style=\"fixed-case\">LAD<\/jats:styled-content>) or<jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>18 deficiency is an autosomal recessive immunodeficiency which has been described in people, cattle, dogs, and knockout mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>The study goals were to characterize the clinicopathologic, immunologic, and molecular genetic features of feline<jats:styled-content style=\"fixed-case\">LAD<\/jats:styled-content>(<jats:styled-content style=\"fixed-case\">FLAD<\/jats:styled-content>) in a neutered male adult Domestic Longhair cat with severe leukocytosis and recurrent infections.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Flow cytometry evaluated surface expression of<jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>18 on neutrophils. In vitro functional assays assessed<jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>18\u2010dependent neutrophil adhesion and T\u2010cell proliferation. Genomic<jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content>and<jats:styled-content style=\"fixed-case\">cDNA<\/jats:styled-content>were used to identify a causative mutation in the coding sequence of the integrin \u03b2<jats:sub>2<\/jats:sub>subunit (<jats:italic><jats:styled-content style=\"fixed-case\">ITGB<\/jats:styled-content>2<\/jats:italic>) gene.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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<jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>18 on the cell surface. Adhesion of affected neutrophils was severely impaired with and without phorbol\u2010myristate\u2010acetate activation. The proband's T\u2010cells proliferated weakly to 1\u00a0pg but normally to 100\u00a0pg staphylococcal enterotoxin A, suggesting a<jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>18\u2010independent T\u2010cell response at higher doses. Molecular genetic analysis of the<jats:italic><jats:styled-content style=\"fixed-case\">ITGB<\/jats:styled-content>2<\/jats:italic>gene revealed a 24\u00a0bp deletion at the exon 2 to intron 2 boundary (c.46_58\u00a0+\u00a011del), predicting premature translational termination due to abnormal splicing of exon 1 to exon 3 or 4.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Feline<jats:styled-content style=\"fixed-case\">LAD<\/jats:styled-content>exhibits features similar to<jats:styled-content style=\"fixed-case\">LAD<\/jats:styled-content>in other species. However, clinical episodes in<jats:styled-content style=\"fixed-case\">FLAD<\/jats:styled-content>appeared milder allowing for an extended life expectancy under long\u2010term antimicrobial therapy, possibly due to an alternative,<jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>18\u2010independent T\u2010cell proliferation pathway.<\/jats:p><\/jats:sec>","DOI":"10.1111\/vcp.12526","type":"journal-article","created":{"date-parts":[[2017,7,27]],"date-time":"2017-07-27T19:02:37Z","timestamp":1501182157000},"page":"391-400","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Feline leukocyte adhesion (<scp>CD<\/scp>18) deficiency caused by a deletion in the integrin \u03b2<sub>2<\/sub>(<i><scp>ITGB<\/scp>2<\/i>) gene"],"prefix":"10.1111","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5614-7333","authenticated-orcid":false,"suffix":"Jr.","given":"Thomas R.","family":"Bauer","sequence":"first","affiliation":[{"name":"Experimental Transplantation and Immunology Branch National Cancer Institute National Institutes of Health Department of Health and Human Services Bethesda MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2568-6032","authenticated-orcid":false,"given":"Suzanne M.","family":"Pratt","sequence":"additional","affiliation":[{"name":"Antech Diagnostics Portland OR USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christina M.","family":"Palena","sequence":"additional","affiliation":[{"name":"Mountain View Veterinary Hospital Vancouver WA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karthik","family":"Raj","sequence":"additional","affiliation":[{"name":"Section\u00a0of Medical Genetics School of Veterinary Medicine University of Pennsylvania Philadelphia PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4770-4107","authenticated-orcid":false,"given":"Urs","family":"Giger","sequence":"additional","affiliation":[{"name":"Section\u00a0of Medical Genetics School of Veterinary Medicine University of Pennsylvania Philadelphia PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,7,27]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.me.38.020187.001135"},{"key":"e_1_2_6_3_1","doi-asserted-by":"crossref","first-page":"1826","DOI":"10.2460\/ajvr.1990.51.11.1826","article-title":"Molecular definition of the bovine granulocytopathy syndrome: identification of deficiency of the Mac\u20101 (CD11b\/CD18) glycoprotein","volume":"51","author":"Kehrli ME,","year":"1990","journal-title":"Am J Vet Res"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1748-5827.2002.tb00032.x"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1939-1676.2002.tb02380.x"},{"key":"e_1_2_6_6_1","first-page":"1622","article-title":"Deficiency of leukocyte surface glycoproteins Mo1, LFA\u20101, and Leu M5 in a dog with recurrent bacterial infections: an animal model","volume":"69","author":"Giger U","year":"1987","journal-title":"Blood"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.188.1.119"},{"key":"e_1_2_6_8_1","first-page":"3955","volume-title":"The Metabolic and Molecular Bases of Inherited Disease","author":"Anderson DC","year":"1995"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1177\/030098589603300303"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/152.4.668"},{"key":"e_1_2_6_11_1","doi-asserted-by":"crossref","first-page":"445","DOI":"10.2460\/javma.1993.202.03.445","article-title":"Clinical manifestations of leukocyte adhesion deficiency in cattle: 14 cases (1977\u20101991)","volume":"202","author":"Gilbert RO","year":"1993","journal-title":"J Am Vet Med Assoc"},{"key":"e_1_2_6_12_1","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.2460\/javma.1983.183.10.1093","article-title":"Granulocytopathy in a Holstein heifer","volume":"183","author":"Hagemoser WA","year":"1983","journal-title":"J Am Vet Med Assoc"},{"key":"e_1_2_6_13_1","first-page":"731","article-title":"Canine granulocytopathy syndrome. 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