Verotoxin targets lymphoma infiltrates of patients with post-transplant lymphoproliferative disease.
Post-transplant lymphoproliferative disease (PTLD) is an invasive, EBV expressing B lymphoma and a major cause of morbidity and mortality following organ transplantation. Presently there is limited therapy available; rather the patient often loses the allograft or succumbs to the malignancy. CD77 (or globotriaosyl ceramide -Gb(3)) is a germinal center B cell marker [Gregory et al. Int J Cancer 1998;42:213-20; Gregory et al., J Immunol 1987;139:313-8; Mangeney et al. Eur J Immunol 1991;21:1131-40], expressed on most EBV infected B cells and is the receptor for the E. coli derived verotoxin (VT) [Lingwood CA. Advances in Lipid Research 1993;25:189-212]. We present the basis of a possible novel approach to PTLD therapy utilizing the specific targeting of VT to the infiltrating lymphoma cells. Biopsies of adenoid, kidney or liver tissue of four PTLD patients were stained with verotoxin to determine expression of CD77. VT is a potent inducer of necrosis/apoptosis of receptor positive cells. In each PTLD case, the infiltrating EBV positive B lymphoma cells were strongly and selectively stained with VT, identifying CD77 as a new marker for these cells. For such individuals, VT might provide the basis of an approach to control their malignancy.
Arbus
G S
GS
Department of Pediatrics (Division of Nephrology), University of Tornoto, Toronto, Ont., Canada.
Grisaru
S
S
Segal
O
O
Dosch
M
M
Pop
M
M
Lala
P
P
Nutikka
A
A
Lingwood
C A
CA
D000293:Adolescent; D001706:Biopsy; D002648:Child; D020031:Epstein-Barr Virus Infections / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D007223:Infant; D016393:Lymphoma, B-Cell / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D016377:Organ Transplantation / Q000009:adverse effects*; D011183:Postoperative Complications / Q000188:drug therapy*; D022603:Shiga Toxins / Q000032:analysis / Q000627:therapeutic use*; D014162:Transfection; D014281:Trihexosylceramides / Q000032:analysis
D022603:Shiga Toxins; D014281:Trihexosylceramides; C018549:globotriaosylceramide