Chemotaxis of non-compressed blood polymorphonuclear leukocytes from an adolescent with severe leukocyte adhesion deficiency.
We have defined the defect in a child with severe leukocyte adhesion deficiency-1 (LAD) as resulting from a single amino acid shift in CD18 (from a C to T mutation at position 533) that prevents heterodimerization with the CD11 antigens to produce beta(2) integrins-the first reported patient homozygous for this defect. Although beset by frequent infections, the patient has survived to adolescence despite the lack of these important adhesion molecules. Consistent with his clinical course is the ability of his PMN to respond chemotactically in slide preparations, albeit with difficulty because of their poor purchase on substrate. The operant adhesins are unknown; his polymorphonuclear leukocytes (PMN) remain chemotactically responsive in the presence of antibodies to alphavbeta(3) and beta(1) integrins and to integrin-associated protein (IAP). These findings indicate that not all patients with severe LAD are candidates for early bone marrow transplantation.
Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520, USA. stephen.malawista@yale.edu
Stephen E
SE
Malawista
Anne
A
de Boisfleury Chevance
Eric J
EJ
Brown
Laurence A
LA
Boxer
S K A
SK
Law
D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001483:Base Sequence / Q000235:genetics; D018821:CD18 Antigens / Q000235:genetics; D019556:COS Cells; D002352:Carrier Proteins / Q000276:immunology; D002448:Cell Adhesion; D002465:Cell Movement; D002634:Chemotaxis, Leukocyte; D002648:Child; D003545:Cysteine; D006720:Homozygote; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000276:immunology; D019012:Integrin beta1 / Q000276:immunology; D018370:Leukocyte-Adhesion Deficiency Syndrome / Q000097:blood* / Q000235:genetics / Q000503:physiopathology; D008297:Male; D009154:Mutation / Q000235:genetics; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D013912:Threonine
D000906:Antibodies; D018821:CD18 Antigens; D002352:Carrier Proteins; D039302:Integrin alphaVbeta3; D019012:Integrin beta1; D013912:Threonine; D003545:Cysteine