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Titolo:
HUMAN RH-D MONOCLONAL-ANTIBODIES (BRAD-3 AND BRAD-5) CAUSE ACCELERATED CLEARANCE OF RH-D-BLOOD-CELLS AND SUPPRESSION OF RH-D IMMUNIZATION IN RH-D- VOLUNTEERS( RED)
Autore:
KUMPEL BM; GOODRICK MJ; PAMPHILON DH; FRASER ID; POOLE GD; MORSE C; STANDEN GR; CHAPMAN GE; THOMAS DP; ANSTEE DJ;
Indirizzi:
INT BLOOD GRP REFERENCE LAB,SOUTHMEAD RD BRISTOL BS10 5ND AVON ENGLAND NATL BLOOD SERV BRISTOL AVON ENGLAND BRISTOL ROYAL INFIRM & GEN HOSP BRISTOL AVON ENGLAND BIO PROD LAB ELSTREE HERTS ENGLAND
Titolo Testata:
Blood
fascicolo: 5, volume: 86, anno: 1995,
pagine: 1701 - 1709
SICI:
0006-4971(1995)86:5<1701:HRM(AB>2.0.ZU;2-J
Fonte:
ISI
Lingua:
ENG
Soggetto:
ANTI-D; FUNCTIONAL-ACTIVITY; QUANTITATION; IMMUNOGLOBULIN; HETEROGENEITY; LYSIS; IGG1;
Tipo documento:
Note
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
44
Recensione:
Indirizzi per estratti:
Citazione:
B.M. Kumpel et al., "HUMAN RH-D MONOCLONAL-ANTIBODIES (BRAD-3 AND BRAD-5) CAUSE ACCELERATED CLEARANCE OF RH-D-BLOOD-CELLS AND SUPPRESSION OF RH-D IMMUNIZATION IN RH-D- VOLUNTEERS( RED)", Blood, 86(5), 1995, pp. 1701-1709

Abstract

The use of prophylactic anti-D to prevent Rh D immunization in Rh D- women and subsequent hemolytic disease in Rh D+ infants is widespread,but has led to shortages of the anti-D lg. With the aim of substituting monoclonal anti-D for Rh D prophylaxis, we have compared the abilities of monoclonal and polyclonal anti-D to clear ph D+ red blood cells(RBCs) infused into Rh D- male volunteers and to suppress Rh D immunization. Two human monoclonal antibodies (MoAbs), BRAD-3 (lgG3) and BRAD-5 (IgG1), produced from stable Epstein-Barr virus-transformed B-lymphoblastoid cell lines, were selected because of their proven in vitro activity in promoting RBC lysis in antibody-dependent cell-mediated cytotoxicity assays. RBC clearance was assessed by intravenous injectionof 3 mL of (51)chromium-labeled D+ RBCs into 27 volunteers 48 hours after intramuscular injection of monoclonal or polyclonal anti-D. Further 3-mL injections of unlabeled D+ cells were administered at 6 and 9 months to induce immunization. Blood samples were taken throughout the12-month period of study for the serologic detection of anti-D. The mean half-life (t(50%)) of RBCs in 7 recipients of 300 mu g BRAD-B (5.9hours) was similar to that in 8 recipients of 500 IU polyclonal anti-D (5.0 hours), whereas D+ cells were cleared more slowly in some of the 8 subjects injected with 300 mu g BRAD-3 (mean t(50%) 12.7 hours) and in 1 individual administered 100 mu g BRAD-3 (t(50%) 41.0 hours). The rate of RBC clearance in both groups administered 300 mu g monoclonal anti-D correlated with the amount of antibody bound per cell, determined by flow cytometry. There was no evidence of primary immunization having occurred in any subject after 6 months of follow-up. Five of 24subjects produced anti-D after one or two further injections of RBCs,confirming that they were responders who had been protected by the monoclonal or polyclonal anti-D administered initially. Four of these responders were recipients of monoclonal anti-D (3 BRAD-3, 1 BRAD-5). One individual who received BRAD-5 produced accelerated clearance of Df RBCs at the third unprotected RBC challenge but did not seroconvert. This study shows that the human MoAbs BRAD-3 and BRAD-5 can prevent Rh D immunization, and indicates that they may be suitable replacements for the polyclonal anti-D presently used in prophylaxis of ph D hemolytic disease of the newborn. This report is one of the first to show thetherapeutic utility of blood group MoAbs. (C) 1995 by The American Society of Hematology.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 24/09/20 alle ore 23:16:38