Roberts W N, Wilson J G, Wong W, Jenkins D E, Fearon D T, Austen K F, Nicholson-Weller A
J Immunol. 1985 Jan;134(1):512-7.
Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hemolytic anemia in which affected erythrocytes (E) are abnormally sensitive to lysis by autologous complement. Affected E from patients with PNH (PNH-E) are deficient in an E membrane regulatory protein of complement, decay-accelerating factor (DAF). Because a functional defect in a second membrane regulatory protein of complement, CR1 (C3b receptor), has also been hypothesized, severely affected PNH-E (type III PNH-E) were tested for abnormalities in CR1 by four methods. E from two patients with 100% type III PNH-E had 3201 and 6783 sites per cell for binding of 125I-labeled rabbit polyclonal F(ab')2 anti-CR1. These values fall within the normal range of CR1 antigenic sites per cell (1267 to 7915, mean = 5,014 +/- 155 SEM) established by assaying the E from 113 healthy donors. The Ka of CR1 on type III PNH-E for 125I-labeled C3b dimer was 2.06 X 10(7) M-1, and the Ka values for the binding of the same ligand to the E from two healthy individuals were 2.45 X 10(7) M-1 and 1.58 X 10(7) M-1. In an assay designed to measure the capacity of human E (Eh) to accelerate the decay of the classical C3 convertase deposited on 1 X 10(7) bystander sheep E (EAC1gp,4bh,2agp), the half-life (t 1/2) of this convertase was diminished from 18.1 min (range 15.2 to 22.9) to 8.1 min (range 7.4 to 8.5) by the addition of 1 X 10(7) normal Eh, to 6.2 min by 100% type III PNH-E, and to 7.5 min by Eh pretreated with an IgG fraction of human antiserum directed against the D antigen of the Rh system. In contrast, Eh (t 1/2 = 7.4) pretreated with a saturating dose of F(ab')2 anti-CR1, and CR1-deficient Eh (less than 10 CR1 molecules/E) from a patient with systemic lupus erythematosus, showed a loss of convertase decay-accelerating capacity to t 1/2 = 11.6 and t 1/2 = 12.4, respectively. Type III PNH-E pretreated with anti-CR1 demonstrated a total loss of their decay-accelerating capacity (t 1/2 = 19.9). In an assay of I cofactor activity, soluble C3b was rapidly converted to iC3b by purified I plus Eh or type III PNH-E, whereas CR1-deficient Eh exhibited less than 5% the I cofactor activity of normal Eh.(ABSTRACT TRUNCATED AT 400 WORDS)
阵发性睡眠性血红蛋白尿（PNH）是一种获得性溶血性贫血，其中受影响的红细胞（E）对自身补体介导的溶解异常敏感。PNH患者的受影响红细胞（PNH-E）缺乏补体的一种红细胞膜调节蛋白，即衰变加速因子（DAF）。由于推测补体的另一种膜调节蛋白CR1（C3b受体）存在功能缺陷，因此采用四种方法对严重受影响的PNH-E（III型PNH-E）的CR1异常进行了检测。两名患有100%III型PNH-E的患者的红细胞，每细胞有3201和6783个位点可结合125I标记的兔多克隆F(ab')2抗CR1。这些值落在通过检测113名健康供者的红细胞所确定的每细胞CR1抗原位点的正常范围内（1267至7915，平均值 = 5014 ± 155 SEM）。III型PNH-E上CR1对125I标记的C3b二聚体的亲和力常数（Ka）为2.06×10⁷ M⁻¹，同一配体与两名健康个体的红细胞结合的Ka值分别为2.45×10⁷ M⁻¹和1.58×10⁷ M⁻¹。在一项旨在测量人红细胞（Eh）加速沉积在1×10⁷个旁观者绵羊红细胞（EAC1gp,4bh,2agp）上的经典C3转化酶衰变能力的试验中，加入1×10⁷个正常Eh后，该转化酶的半衰期（t₁/₂）从18.1分钟（范围15.2至22.9）缩短至8.1分钟（范围7.4至8.5），加入100%III型PNH-E后缩短至6.2分钟，加入用针对Rh系统D抗原的人抗血清的IgG部分预处理的Eh后缩短至7.5分钟。相比之下，用饱和剂量的F(ab')2抗CR1预处理的Eh（t₁/₂ = 7.4）以及来自一名系统性红斑狼疮患者的CR1缺陷型Eh（每红细胞少于10个CR1分子），其转化酶衰变加速能力分别丧失至t₁/₂ = 11.6和t₁/₂ = 12.4。用抗CR1预处理的III型PNH-E表现出其衰变加速能力完全丧失（t₁/₂ = 19.9）。在I辅因子活性测定中，可溶性C3b通过纯化的I加上Eh或III型PNH-E迅速转化为iC3b，而CR1缺陷型Eh的I辅因子活性不到正常Eh的5%。（摘要截短于400字）
