McHugh N J, Whyte J, Artlett C, Briggs D C, Stephens C O, Olsen N J, Gusseva N G, Maddison P J, Black C M, Welsh K
Bath Institute for Rheumatic Diseases, Trimbridge, UK.
Clin Exp Immunol. 1994 May;96(2):267-74. doi: 10.1111/j.1365-2249.1994.tb06552.x.
Autoantibody reactivity to centromere proteins CENP-A, CENP-B and CENP-C was examined in 58 patients with systemic sclerosis (SSc), 218 first degree relatives and 22 spouses. HLA class II typing for HLA-DRB1 and HLA-DQA1 was performed by restriction fragment length polymorphism (RFLP) analysis in 50 families, and HLA-DRB1, HLA-DQA1 and HLA-DQB1 typing was performed by olignucleotide typing in 44 families. Eleven probands and two relatives had ACA. The two relatives with ACA also had SSc. One relative was an identical twin sister of a proband with ACA and the other relative was a sister of a proband with ACA. All ACA-positive probands and relatives were female, and all recognized CENP-A, CENP-B and CENP-C. The presence of at least one HLA-DQB1 allele not coding for leucine at position 26 of the first domain appeared necessary, although not sufficient for the generation of ACA. Therefore within SSc families ACA is strongly associated with female gender and disease phenotype, and is at least in part genetically determined.
在58例系统性硬化症（SSc）患者、218名一级亲属和22名配偶中检测了抗着丝粒蛋白CENP - A、CENP - B和CENP - C的自身抗体反应性。对50个家庭通过限制性片段长度多态性（RFLP）分析进行HLA - DRB1和HLA - DQA1的HLA II类分型，对44个家庭通过寡核苷酸分型进行HLA - DRB1、HLA - DQA1和HLA - DQB1分型。11名先证者和2名亲属有抗着丝粒抗体（ACA）。这两名有ACA的亲属也患有SSc。一名亲属是一名有ACA先证者的同卵双胞胎姐妹，另一名亲属是一名有ACA先证者的姐妹。所有ACA阳性的先证者和亲属均为女性，且均识别CENP - A、CENP - B和CENP - C。虽然对于ACA的产生来说不充分，但第一结构域第26位不编码亮氨酸的至少一个HLA - DQB1等位基因的存在似乎是必要的。因此，在SSc家族中，ACA与女性性别和疾病表型密切相关，并且至少部分是由基因决定的。
