Cornille-Brøgger R, Fleming A F, Kagan I, Matsushima T, Molineaux L
Ann Trop Med Parasitol. 1979 Apr;73(2):173-83. doi: 10.1080/00034983.1979.11687244.
Children born in areas hyperendemic for Plasmodium falciparum are protected by maternal antibodies for up to about five months of life, after which they are subject to intense infection until they acquire sufficient immunity--by about five years of age. Children with sickle cell trait (Hb.AS) are at an advantage during these critical years, probably because of preferential phagocytosis of parasitized red cells. This could lead to either (i) early processing of antigen by macrophages and an accelerated immune response, or (ii) less antigenic stimulus and hence lower antibody production. Immunoglobulin (Ig)G and IgM determinations, agar gel diffusion (Ouchterlony) against soluble P. falciparum antigen, the indirect fluorescent antibody (IFA) test using P. falciparum and P. malariae antigens, and the indirect haemagglutination (IHA) test with P. falciparum antigen were performed on sera from a population with different Hb electrophoretic types in the hyperendemic malarial area of Garki, Kano State, Nigeria. Plasma immunoglobulins and antimalarial antibodies rose with age. After the first year of life, lower mean concentrations of immunoglobulins (especially IgM), and lower mean titres of antibodies specific against P. falciparum (Ouchterlony, IHA and less significantly IFA) were present in Hb.AS compared to Hb.AA; these differences increased with age. Antimalarial intervention was followed by a decline of all values and final levels showed little difference between haemoglobin types. It was unlikely that either a relative inability to produce antibody or a more rapid catabolism of immunoglobulins was responsible for the lower levels in sickle cell trait. The observations are more easily explained by the hypothesis that Hb.AS persons have less antigenic stimulus due to the early removal of parasitized sickled cells by macrophages, which then degrade the antigens. The antibody difference between Hb.AA and Hb.AS increased throughout life, suggesting that this process remained a feature of sickle cell trait even after parasite frequencies and densities were similar in the two Hb groups. These observations have implications in the aetiology of tropical splenomegaly syndrome, which is rarely seen in sickle cell trait subjects. Mean IgG and IgM were slightly higher in Hb.AS than Hb.AA infants, the difference for IgG achieving significance. This suggested that during infancy early phagocytosis of parasitized cells had led to enhanced processing of antigen and hence an earlier immune response in Hb.AS, but this was unlikely to be a major factor in survival. IFA titres against P. malariae were slightly but not significantly lower in Hb.AS, possibly as a result of cross-reaction with P. falciparum antibody or of a slight degree of protection against P. malariae.
在恶性疟原虫高度流行地区出生的儿童，在出生后的大约五个月内受到母体抗体的保护，此后他们会受到严重感染，直到大约五岁获得足够免疫力为止。具有镰状细胞性状（Hb.AS）的儿童在这些关键年份具有优势，这可能是因为被寄生红细胞的优先吞噬作用。这可能导致以下两种情况之一：（i）巨噬细胞对抗原的早期处理和加速的免疫反应，或者（ii）较少的抗原刺激，从而导致较低的抗体产生。对尼日利亚卡诺州加尔基疟疾高度流行地区不同Hb电泳类型人群的血清进行了免疫球蛋白（Ig）G和IgM测定、针对可溶性恶性疟原虫抗原的琼脂凝胶扩散（奥克特洛尼）试验、使用恶性疟原虫和间日疟原虫抗原的间接荧光抗体（IFA）试验以及使用恶性疟原虫抗原的间接血凝（IHA）试验。血浆免疫球蛋白和抗疟抗体随年龄增长而升高。在生命的第一年之后，与Hb.AA相比，Hb.AS人群中免疫球蛋白（尤其是IgM）的平均浓度较低，以及针对恶性疟原虫的特异性抗体的平均滴度较低（奥克特洛尼试验、IHA试验，IFA试验的差异较小）；这些差异随着年龄的增长而增加。抗疟干预后所有值均下降，最终水平在不同血红蛋白类型之间差异不大。镰状细胞性状人群中抗体水平较低不太可能是由于相对无法产生抗体或免疫球蛋白的分解代谢更快所致。这些观察结果更容易用以下假设来解释：由于巨噬细胞早期清除被寄生的镰状细胞，Hb.AS个体受到的抗原刺激较少，然后巨噬细胞会降解这些抗原。Hb.AA和Hb.AS之间的抗体差异在整个生命过程中都在增加，这表明即使在两组Hb人群中寄生虫频率和密度相似之后，这个过程仍然是镰状细胞性状的一个特征。这些观察结果对热带脾肿大综合征的病因学有影响，该综合征在镰状细胞性状个体中很少见。Hb.AS婴儿的平均IgG和IgM略高于Hb.AA婴儿，IgG的差异具有统计学意义。这表明在婴儿期，被寄生细胞的早期吞噬导致抗原处理增强，从而使Hb.AS个体产生更早的免疫反应，但这不太可能是生存的主要因素。Hb.AS个体针对间日疟原虫的IFA滴度略低但无统计学意义，这可能是由于与恶性疟原虫抗体的交叉反应或对间日疟原虫有轻微程度的保护作用。
