Discontinuation of fucose therapy in LADII causes rapid loss of selectin ligands and rise of leukocyte counts.
Leukocyte adhesion deficiency type II (LADII) is a rare inherited disorder of fucose metabolism. Patients with LADII lack fucosylated glycoconjugates, including the carbohydrate ligands of the selectins, leading to an immunodeficiency caused by the lack of selectin-mediated leukocyte-endothelial interactions. A simple and effective therapy has recently been described for LADII, based on the administration of oral fucose. Parallel to this treatment the lack of E- and P-selectin ligands on neutrophils was corrected, and high peripheral neutrophil counts were reduced to normal levels. This study reports that discontinuation of this therapy leads to the complete loss of E-selectin ligands within 3 days and of P-selectin ligands within 7 days. Peripheral neutrophil counts increased parallel to the decrease of selectin ligands. Selectin ligands reappeared promptly after resumption of the fucose therapy, demonstrating a causal relationship between fucose treatment and selectin ligand expression and peripheral neutrophil counts.
Lühn
K
K
Institute of Cell Biology, ZMBE, University of Münster; Max-Planck-Institute for Physiological and Clinical Research, Münster, Germany.
Marquardt
T
T
Harms
E
E
Vestweber
D
D
D005643:Fucose / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007223:Infant; D007958:Leukocyte Count; D018370:Leukocyte-Adhesion Deficiency Syndrome / Q000097:blood / Q000188:drug therapy*; D008024:Ligands; D008297:Male; D009504:Neutrophils / Q000737:chemistry / Q000166:cytology; D019087:Selectins / Q000187:drug effects / Q000378:metabolism
D008024:Ligands; D019087:Selectins; D005643:Fucose