IMMUNOLOGICAL HETEROGENEITY OF HEMOPHILIA-B - MULTICENTER STUDY OF 98 KINDREDS

Summary. An electroimmunoassay with a precipitating rabbit anti‐human factor IX antiserum and an inhibitor neutralization assay with a non‐precipitating homologous antibody were used to measure factor IX antigen (IX:Ag) in 117 patients from 98 kindreds with haemophilia B; and to investigate in a mixed population the incidence of different immunological types of the disease. Although the two assays showed an excellent correlation, the electroimmunoassay was selected for its simplicity as a criterion for classification. 52 kindreds, referred to as haemophilia B‐, were characterized by severe deficiency of factor IX coagulant activity (<0.01‐0.03 u/ml) and unmeasurable IX:Ag (< 0.12 u/ml): this genetic variant of the disease appears to be related to a complete or marked suppression of factor IX synthesis. In 16 kindreds, a severe or moderately severe IX:C deficiency was associated with normal or increased levels of IX:Ag (haemophilia B+): among them, a subgroup of five kindreds could be identified by the additional abnormality of a prolonged Thrombotest clotting time (haemophilia BM). These patients are likely to be the expression of normal or increased synthesis of a factor IX molecule markedly defective in the site(s) responsible for coagulant activity. Reduced levels of IX:Ag (0.12‐0.65 u/ml) characterized the remaining 30 kindreds, presenting with IX: C levels ranging from < 0.01 to 0.21 u/ml. In 28 there was a significant excess of IX:Ag over IX:C, suggesting a reduced capacity to synthesize the factor IX molecule accompanied by a variable defect in the coagulant site; the remaining two kindreds, which showed a concomitant reduction of IX:C and IX:Ag, are likely to be examples of a true reduction of factor IX synthesis. Copyright © 1978, Wiley Blackwell. All rights reserved