Detection and IgG subclass analysis of antibodies to factor VIII in multitransfused haemophiliacs and healthy individuals

被引:13
作者
Gautier, P
Sultan, Y
ParquetGernez, A
Meriane, F
Guerois, C
Derlon, A
机构
[1] HOP COCHIN,CTR ACCUEIL & TRAITEMENT HEMOPHILES,F-75674 PARIS,FRANCE
[2] CTR REG TRANSFUS LILLE,LILLE,FRANCE
[3] CTR TRANSFUS BAB EL OUED,ALGIERS,ALGERIA
[4] HOP TROUSSEAU,HEMATOL LAB,TOURS,FRANCE
关键词
anti factor VIII antibodies; factor VIII inhibitors; IgG subclasses; micro ELISA method; haemophilia A; healthy individuals;
D O I
10.1111/j.1365-2516.1996.tb00021.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Using a binding assay to immobilized factor VIII (F VIII) (ELISA) we measured the amount of Ige with binding capacity to FVIII, in the plasma of patients with an inhibitor to F VIII, in multitransfused haemophiliacs without inhibitor and in a control group of blood donors. It was shown that the amount of IgG bound to VIII was elevated in patients with an inhibitor although a weak correlation could be established between the inhibitor titre (BU) and the amount of bound IgG. In all haemophiliacs without inhibitor, Ige bound to F VIII were present. Although the mean value of IgG bound to F VIII was significantly lower than the amount detected in patients with F VIII inhibitors, a group of patients developed an equal amount of IgG recognizing the F VIII molecules to the amount of IgG measured in inhibitor patients. These results indicate that the presence of an inhibitor is not related to the amount of specific Ige bound to F VIII but more likely to the position of epitopes recognized by specific IgG. The presence of IgG bound to F VIII was detected in 92% of control blood donors and an inhibitor to F VIII ranging from 0.5 to 1.3 BU mL(-1) in 17% of them. The isotypes of bound immunoglobins were identified in patients and controls: IgG4 subclass was predominant only in patients with an inhibitor and usually associated with antibodies of one or more of the other subclasses. In noninhibitor patients, very few had antibodies of IgG4 subclass with binding capacity to F VIII. These results raised the question of the clinical significance of these antibodies in multitransfused patients. The study indicates that binding assay is a complementary test to be used in multitransfused patients but cannot be used instead of the coagulation tests for detection of inhibitors.
引用
收藏
页码:88 / 94
页数:7
相关论文
共 22 条
[1]   NATURAL ANTIBODIES TO FACTOR-VIII (ANTI-HEMOPHILIC FACTOR) IN HEALTHY-INDIVIDUALS [J].
ALGIMAN, M ;
DIETRICH, G ;
NYDEGGER, UE ;
BOIELDIEU, D ;
SULTAN, Y ;
KAZATCHKINE, MD .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (09) :3795-3799
[2]   GAMMA G4-GLOBULIN ANTIBODY CAUSING INHIBITION OF CLOTTING FACTOR 8 [J].
ANDERSEN, BR ;
TERRY, WD .
NATURE, 1968, 217 (5124) :174-&
[3]   MOLECULAR-BASIS OF FACTOR-VIII INHIBITION BY HUMAN-ANTIBODIES - ANTIBODIES THAT BIND TO THE FACTOR-VIII LIGHT CHAIN PREVENT THE INTERACTION OF FACTOR-VIII WITH PHOSPHOLIPID [J].
ARAI, M ;
SCANDELLA, D ;
HOYER, LW .
JOURNAL OF CLINICAL INVESTIGATION, 1989, 83 (06) :1978-1984
[4]  
BATTLE J, 1993, THROMB HAEMOSTASIS, V69, P557
[5]  
CAMPBELL W, 1988, BLOOD, V71, P344
[6]  
DIETRICH G, 1992, BLOOD, V79, P2946
[7]  
FOSTER PA, 1990, BLOOD, V75, P1999
[8]   GENETIC PREDISPOSITION TO DEVELOP FACTOR-VIII ANTIBODY IN CLASSIC HEMOPHILIA [J].
FROMMEL, D ;
ALLAIN, JP .
CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY, 1977, 8 (01) :34-38
[9]  
FULCHER CA, 1987, BLOOD, V69, P1475
[10]   LOCALIZATION OF HUMAN FACTOR-FVIII INHIBITOR EPITOPES TO 2 POLYPEPTIDE FRAGMENTS [J].
FULCHER, CA ;
MAHONEY, SD ;
ROBERTS, JR ;
KASPER, CK ;
ZIMMERMAN, TS .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1985, 82 (22) :7728-7732