Immunological Heterogeneity of Haemophilia B: a Multicentre Study of 98 Kindreds
Immunological Heterogeneity of Haemophilia B: a Multicentre Study of 98 Kindreds
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B 型血友病的免疫异质性：98 个家族的多中心研究
DOI：
10.1111/j.1365-2141.1978.tb05840.x
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发表时间：
1978
影响因子：
6.5
通讯作者：
Z. Ruggeri
中科院分区：
文献类型：
--
作者：
V. Parekh;P. Mannucci;Z. Ruggeri
摘要采用沉淀性兔抗人因子IX抗血清的电免疫测定和非沉淀性同源抗体的抑制剂中和试验，测定了98例血友病B患者中117例患者的因子IX抗原（IX：Ag）;并研究了混合人群中不同免疫学类型疾病的发病率。虽然这两种测定法显示出良好的相关性，但选择电免疫测定法作为分类标准是因为其简单。52例血友病，称为血友病B-，其特征为因子IX凝血活性严重缺乏（<0.01 - 0.03 u/ml）和不可测量的IX：Ag（< 0.12 u/ml）：这种疾病的遗传变异似乎与因子IX合成的完全或显著抑制有关。在16个kinemas中，重度或中度IX：C缺乏与IX：Ag水平正常或升高相关（血友病B+）：其中，5个kinemas亚组可通过血栓试验凝血时间延长的额外异常（血友病BM）确定。这些患者很可能是正常表达或增加合成的因子IX分子在负责凝血活性的位点明显缺陷。IX：Ag水平降低（0.12 - 0.65 u/ml）表征了其余30种激酶，IX：C水平范围为< 0.01 - 0.21 u/ml。在28中，IX：Ag显著超过IX：C，表明合成因子IX分子的能力降低，伴随着凝血位点的可变缺陷;其余两种激酶，显示IX：C和IX：Ag的伴随减少，可能是因子IX合成真正减少的例子。
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.