Granoff D M, Pandey J P, Boies E, Squires J, Munson R S, Suarez B
J Clin Invest. 1984 Nov;74(5):1708-14. doi: 10.1172/JCI111588.
In experimental animals, immune responses to certain antigens are regulated by immunoglobulin allotype-linked genes. In an effort to detect such genes in humans, we examined the antibody responses of 74 healthy children with different Km(1) or Gm(23) allotypes to a Haemophilus influenzae type b vaccine (type b polysaccharide capsule-pertussis vaccine). The anticapsular antibody responses of black or white children with the Km(1) allotype were 4.6- to 9.5-fold higher than those of children who lacked this determinant (P less than 0.004). No significant differences were found in antibody response with respect to the Gm(23) allotype. The frequencies of Km(1) and Gm(23) also were examined in 170 patients with Haemophilus meningitis, 71 patients with epiglottitis, and 173 control children. Km(1) was detected less frequently in black patients with meningitis (38%) than in those with epiglottitis (81%, P less than 0.002) or in controls (66%, P less than 0.0007). The relative risk of meningitis thus was 3.2-fold lower among black children with the Km(1) allotype than in those who lacked this allotype (odds ratio = 0.3, 95% confidence interval 0.2 to 0.6). However, the risk of meningitis was not decreased in white children with the Km(1) allotype (odds ratio = 1.0). There were no significant differences in the frequency of Gm(23) among the patient groups and controls. The Km(1) allotype but not the Gm(23) thus defines a subpopulation of children of both races who are high responders to this vaccine, and black children but not white children with the Km(1) allotype are at decreased risk of developing Haemophilus meningitis. These data indicate that in blacks, genes associated with Km(1) may affect immune response to a prototype type b Haemophilus vaccine, and perhaps interact with another factor related to race to affect susceptibility to Haemophilus meningitis.
在实验动物中，对某些抗原的免疫反应受免疫球蛋白同种异型连锁基因调控。为了在人类中检测此类基因，我们检测了74名具有不同Km(1)或Gm(23)同种异型的健康儿童对b型流感嗜血杆菌疫苗（b型多糖荚膜 - 百日咳疫苗）的抗体反应。具有Km(1)同种异型的黑人或白人儿童的抗荚膜抗体反应比缺乏该决定簇的儿童高4.6至9.5倍（P小于0.004）。关于Gm(23)同种异型，未发现抗体反应有显著差异。我们还检测了170例流感嗜血杆菌脑膜炎患者、71例会厌炎患者和173名对照儿童中Km(1)和Gm(23)的频率。脑膜炎黑人患者中Km(1)的检出频率（38%）低于会厌炎患者（81%，P小于0.002）或对照儿童（66%，P小于0.0007）。因此，具有Km(1)同种异型的黑人儿童患脑膜炎相对风险比缺乏该同种异型的儿童低3.2倍（优势比 = 0.3，95%置信区间0.2至0.6）。然而，具有Km(1)同种异型的白人儿童患脑膜炎风险并未降低（优势比 = 1.0）。患者组和对照组中Gm(23)的频率无显著差异。因此，Km(1)同种异型而非Gm(23)确定了两个种族中对该疫苗反应强烈的儿童亚群，并且具有Km(1)同种异型的黑人儿童而非白人儿童患流感嗜血杆菌脑膜炎的风险降低。这些数据表明，在黑人中，与Km(1)相关的基因可能影响对b型流感嗜血杆菌原型疫苗的免疫反应，并且可能与另一个与种族相关的因素相互作用，影响对流感嗜血杆菌脑膜炎的易感性。
