Serjeantson S W, Crane G G
John Curtin School of Medical Research, Australian National University, Canberra.
Hum Biol. 1991 Apr;63(2):115-28.
Hyperreactive malarious splenomegaly (HMS) reflects abnormal immune responses to malarial infection. The central question is whether HMS results from unusual patterns of malarial infection or from immune incompetence in the host. Family distributions of two features of the syndrome, splenomegaly and excessively high IgM levels, have been examined in a Papau New Guinea population in which HMS is exceptionally common. Segregation analysis of spleen grade shows that a major sex-linked gene controls hyperresponsiveness to malaria. This finding is supported by additional segregation analysis, which shows that an autosomal locus cannot account for a significant proportion of variation in spleen grade, and by path analysis, which rejects a model that assumes that parents contribute equally to the child's genotype. The sex-linked gene contributing to HMS was not mediated through sex linkage of a major gene for IgM concentrations, as shown by segregation analysis. It has yet to be determined whether this pattern of inheritance also applies to HMS occurring sporadically in other less severely affected populations. The applicability of these findings to the general variability in "normal" IgM responses to malaria also remains to be established.
高反应性疟疾性脾肿大（HMS）反映了对疟疾感染的异常免疫反应。核心问题在于HMS是由疟疾感染的异常模式引起，还是由宿主的免疫功能不全导致。在HMS异常常见的巴布亚新几内亚人群中，对该综合征的两个特征——脾肿大和IgM水平过高——的家族分布情况进行了研究。脾脏分级的分离分析表明，一个主要的性连锁基因控制着对疟疾的高反应性。这一发现得到了进一步分离分析的支持，该分析表明常染色体位点无法解释脾脏分级中很大比例的变异；同时也得到了通径分析的支持，通径分析否定了父母对孩子基因型贡献相等的模型。如分离分析所示，导致HMS的性连锁基因并非通过IgM浓度主要基因的性连锁介导。这种遗传模式是否也适用于在其他受影响较轻人群中散发性出现的HMS，还有待确定。这些发现对于“正常”疟疾IgM反应的一般变异性的适用性也有待确立。
