Bottaro A, DeMarchi M, DeLange G G, Boccazzi C, Fubini L, Borra C, Cappello N, Carbonara A O
Dipartimento di Genetica, Biologia e Chimica Medica, Università di Torino, Italy.
Eur J Immunol. 1989 Nov;19(11):2159-62. doi: 10.1002/eji.1830191128.
In man, IgG4 is the least abundant of the four IgG subclasses, and its serum levels vary considerably from one subject to another. Its deficiency has been thought to lead to recurrent infections; nevertheless, it is also commonly found in healthy individuals (1/400 in the Italian population). In 39 subjects with IgG4 serum levels less than 1 microgram/ml, we used 4 different probes (described in the accompanying study, Bottaro et al., Eur. J. Immunol. 1989. 19: 2151) to examine 13 loci within the IGHC region and analyzed the RFLP for 7 of them. No aberrant restriction patterns were identified in any of the subjects, showing the absence of major IGHC structural alterations. The allele frequency of some loci, however, was significantly different from that of a control group of 95 random subjects. This variation was shown to depend on a selective increase in the number of homozygotes for the associated alleles, that reached significant levels for the IGHGP, G2, PG2, PG4 and SG4 loci, but not for SG1 and A2T. The highest value was reached for alleles in the PG4 region, just 5' of SG4. These data indicate that a minor structural IGHC defect is probably the cause of a significant fraction of IgG4 deficiencies. Moreover, the different association levels of the PG4 and SG4 regions suggest that this defect is likely to lie in an upstream regulatory region rather than in the structural G4 gene.
在人类中，IgG4是四种IgG亚类中含量最少的，其血清水平在个体之间差异很大。人们认为其缺乏会导致反复感染；然而，在健康个体中也普遍存在（意大利人群中为1/400）。在39名IgG4血清水平低于1微克/毫升的受试者中，我们使用4种不同的探针（在随附研究中描述，Bottaro等人，《欧洲免疫学杂志》，1989年。19: 2151）检测IGHC区域内的13个位点，并分析其中7个位点的限制性片段长度多态性（RFLP）。在任何受试者中均未发现异常的限制性图谱，表明不存在主要的IGHC结构改变。然而，一些位点的等位基因频率与95名随机受试者的对照组有显著差异。这种差异被证明取决于相关等位基因纯合子数量的选择性增加，对于IGHGP、G2、PG2、PG4和SG4位点达到显著水平，但对于SG1和A2T位点则未达到。PG4区域（就在SG4的5'端）的等位基因达到最高值。这些数据表明，IGHC的微小结构缺陷可能是相当一部分IgG4缺乏的原因。此外，PG4和SG4区域不同的关联水平表明，这种缺陷可能位于上游调控区域而非结构G4基因中。
