Saethre Marit, Sølvik Una Ø, Haraldsen Guttorm, Fiane Arnt E, Boretti Eva, Thorsby Erik, Platt Jeffrey L, Mollnes Tom E
Institute of Immunology, University of Oslo, Norway.
Xenotransplantation. 2002 Sep;9(5):350-8. doi: 10.1034/j.1399-3089.2002.01094.x.
Naturally occurring anti-Galalpha1-3Gal (anti-Gal) antibodies and complement induce hyperacute rejection (HAR) of porcine organs transplanted to primates. If the hyperacute reaction is prevented, an acute vascular rejection (AVR) occurs within hours to few days. Antibodies are important for the development of AVR, whereas the role of complement is still not clarified. AVR is characterized by protein synthesis-dependent endothelial cell (EC) activation. In the present study we investigated the relation between EC activation as measured by E-selectin expression, and the concentrations of anti-Gal antibodies of IgM, IgG and IgG subclasses in sera from 80 healthy blood donors selected on the basis of sex and age. There was a significant correlation between E-selectin expression and the concentration of IgG3 anti-Gal (r=0.39; P=0.019), which was not seen for the other IgG subclasses or for total IgG anti-Gal. A modest, but significant correlation was found between the concentration of IgM anti-Gal and E-selectin expression (r=0.38; P=0.040), but not between IgM and IgG3 anti-Gal. There was a large interindividual variation in anti-Gal antibodies, 50-fold for IgM and 70-fold for IgG. Females had significantly higher concentrations of IgM anti-Gal than males (P=0.0006), which was explained by a substantial increase in IgM anti-Gal concentration in younger women. The concentration of IgG anti-Gal and the degree of E-selectin expression did not differ between sex or age groups. In conclusion, the close correlation between anti-Gal antibodies of the potent complement activating IgG3 subclass and porcine EC activation, may imply that these antibodies play a role in EC activation characteristic of AVR.
天然存在的抗半乳糖α1-3半乳糖（抗Gal）抗体和补体可诱导移植到灵长类动物体内的猪器官发生超急性排斥反应（HAR）。如果超急性反应得到预防，数小时至数天内会发生急性血管排斥反应（AVR）。抗体对AVR的发生很重要，而补体的作用仍不清楚。AVR的特征是蛋白合成依赖性内皮细胞（EC）活化。在本研究中，我们调查了通过E-选择素表达测量的EC活化与80名根据性别和年龄选择的健康献血者血清中IgM、IgG和IgG亚类抗Gal抗体浓度之间的关系。E-选择素表达与IgG3抗Gal浓度之间存在显著相关性（r = 0.39；P = 0.019），而其他IgG亚类或总IgG抗Gal则未观察到这种相关性。发现IgM抗Gal浓度与E-选择素表达之间存在适度但显著的相关性（r = 0.38；P = 0.040），但IgM和IgG3抗Gal之间没有相关性。抗Gal抗体存在很大的个体差异，IgM为50倍，IgG为70倍。女性的IgM抗Gal浓度显著高于男性（P = 0.0006），这是由于年轻女性中IgM抗Gal浓度大幅增加所致。不同性别或年龄组之间的IgG抗Gal浓度和E-选择素表达程度没有差异。总之，具有强大补体激活能力的IgG3亚类抗Gal抗体与猪EC活化之间的密切相关性可能意味着这些抗体在AVR特征性的EC活化中起作用。
