Leukocyte adhesion deficiency II syndrome, a generalized defect in fucose metabolism - PubMed (original) (raw)

Case Reports

doi: 10.1016/s0022-3476(99)70281-7.

T Brune, K Lühn, K P Zimmer, C Körner, L Fabritz, N van der Werft, J Vormoor, H H Freeze, F Louwen, B Biermann, E Harms, K von Figura, D Vestweber, H G Koch

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Case Reports

Leukocyte adhesion deficiency II syndrome, a generalized defect in fucose metabolism

T Marquardt et al. J Pediatr. 1999 Jun.

Abstract

Leukocyte adhesion deficiency II has been described in only 2 patients; herein we report extensive investigation of another patient. The physical stigmata were detected during prenatal ultrasonographic investigation. Sialyl-Lewis X (sLex) was absent from the surface of polymorphonuclear neutrophils, and cell binding to E- and P-selectin was severely impaired, causing an immunodeficiency. The elevation of peripheral neutrophil counts occurred within several days after birth. A severe hypofucosylation of glycoconjugates bearing fucose in different glycosidic links was present in all cell types investigated, demonstrating that leukocyte adhesion deficiency II is not only a disorder of leukocytes but a generalized inherited metabolic disease affecting the metabolism of fucose.

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Figures

Fig. 1

Fig. 1

Pedigree of the patient’s family. A, B, and C are small villages in a circumscribed area near the Black Sea. dm, Deaf.

Fig. 2

Fig. 2

Clinical stigmata. Long eyelashes, a broad and depressed nasal bridge, a simian crease, and dorsally positioned second toes are the clinical stigmata of the patient with LAD II. The depressed nasal bridge was already seen on intrauterine ultrasonographic investigation in the 28th week of gestation (lower right panel) .

Fig. 3

Fig. 3

Magnetic resonance imaging scan of the brain. Frontal cerebral atrophy was present at 6 months of age.

Fig. 4

Fig. 4

Leukocyte counts and C-reactive protein. Total peripheral leukocyte counts of the patient (left panel) and differential counts (middle panel) . Concentration of C-reactive protein in the serum (right panel) . Normal values: leukocytes, 6000 to 17,000/μL; neutrophils, 1500 to 8500/μL; lymphocytes 4000 to 10,500/μL; C-reactive protein, <1 mg/dL.

Fig. 5

Fig. 5

FACS analysis. A, FACS analysis of CD14 and CD15 antigens. Red, lymphocytes; blue, granulocytes; green, monocytes. Granulocytes and lymphocytes of the patient with LAD II do not express the CD15 antigen. B, Analysis of granulocytes with monoclonal CSLEX-1 antibody. Background fluorescence with secondary antibody is shown in black . The fluorescent signal obtained with CSLEX-1 antibody (shown in red ) is absent in LAD II cells. C, E-selectin binding to granulocytes. Background fluorescence with the streptavidin detection reagent is shown in black . A soluble fusion protein of E-selectin and the Fc part of IgG was used for incubations. To control for unspecific binding to unblocked Fc receptors on the cell surface, a VE-cadherin-IgG fusion protein was used (blue) . VE-cadherin does not have a specific binding to neutrophil surface antigens. Because binding of selectins to their ligands is Ca2+-dependent, selectin binding was investigated both in the presence (red) and absence (green) of calcium. In control cells, selectin binding, which can be completely suppressed in the absence of calcium, occurs. In LAD II cells, very little selectin binding is observed, which does not change in the absence of divalent cations. D, P-selectin binding. In contrast to control cells, only a small decrease of P-selectin binding was observed in the absence of calcium. E, H-antigen expression on erythrocytes.

Fig. 6

Fig. 6

Electron microscopy. UEA binding sites visualized by immunogold in neutrophil granulocytes (upper 2 panels) and thrombocytes (lower 2 panels) . Photographs at left are from a healthy control subject; those at right are from the patient with LAD II, showing a considerably reduced number of lectin binding sites.

Fig. 7

Fig. 7

Lens culinaris binding of glycopeptides from fibroblasts after mannose labeling. After sample application, the column was washed to remove labeled material that was not specifically bound to the column. Maximal counts were present in the first 2 fractions of the void volume (with 12,000 cpm in second fraction from controls and 13,000 cpm in second fraction from LAD II cells; peaks are cut off in the diagram). On addition of methyl mannopyranoside, labeled glycopeptides were eluted in controls, whereas very few counts were eluted from LAD II cells. Circles, Controls; squares, LAD II cells.

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