Briggs D C, Senaldi G, Isenberg D A, Welsh K I, Vergani D
Tissue Typing Laboratory, Guy's Hospital, London.
Ann Rheum Dis. 1991 Apr;50(4):251-4. doi: 10.1136/ard.50.4.251.
Deficiencies of early components of the classical complement pathway are known to be associated with systemic lupus erythematosus (SLE). C4 null alleles, C4A Q0 and C4B Q0, are prime candidates for the major histocompatibility complex associated factor which determines susceptibility to SLE. There is poor correlation, however, between the presence of low concentrations of C4 and possession of C4 null alleles, and thus the basis of the association between C4A Q0, C4B Q0 and SLE remains obscure. The possibility that activation of C4 may be related to the possession of C4 null alleles was examined. C4 phenotypes were investigated, and C4 concentration and activation were estimated in patients with SLE. C4 activation was determined by measuring the concentration of C4d--a split product of C4. Twenty five of 35 patients had C4 phenotypes which include null alleles. No association between low C4 concentrations and C4 null alleles was found, but a significant association between low C4d concentrations and C4 phenotypes including null alleles, particularly those with C4A Q0, was noted. No correlation between concentrations of C4 and C4d was found. These results show an influence of C4 null alleles on the activation of the C4 molecule, which is independent of the concentration of C4. The possession of silent genes coding for C4 null alleles might predispose to SLE by conditioning poor C4 activation, a critical event for the clearance of immune complexes mediated by the classical complement pathway.
已知经典补体途径早期成分的缺陷与系统性红斑狼疮（SLE）相关。C4无效等位基因C4A Q0和C4B Q0是决定SLE易感性的主要组织相容性复合体相关因子的主要候选基因。然而，低浓度C4的存在与C4无效等位基因的携带之间的相关性较差，因此C4A Q0、C4B Q0与SLE之间关联的基础仍不清楚。研究了C4激活可能与C4无效等位基因携带有关的可能性。对SLE患者的C4表型进行了研究，并对C4浓度和激活情况进行了评估。通过测量C4d（C4的裂解产物）的浓度来确定C4激活。35名患者中有25名具有包括无效等位基因的C4表型。未发现低C4浓度与C4无效等位基因之间存在关联，但注意到低C4d浓度与包括无效等位基因的C4表型之间存在显著关联，尤其是那些具有C4A Q0的表型。未发现C4浓度与C4d浓度之间存在相关性。这些结果表明C4无效等位基因对C4分子的激活有影响，这与C4浓度无关。编码C4无效等位基因的沉默基因的携带可能通过导致C4激活不良而使个体易患SLE，C4激活不良是经典补体途径介导的免疫复合物清除的关键事件。
