Arnett F C, Reveille J D, Moutsopoulos H M, Georgescu L, Elkon K B
University of Texas-Houston Health Science Center, USA.
Arthritis Rheum. 1996 Nov;39(11):1833-9. doi: 10.1002/art.1780391109.
To determine the frequencies and clinical associations of antiribosomal P antibodies (anti-P) in a large multiethnic cohort of patients with systemic lupus erythematosus (SLE), and to assess whether anti-P was associated with any major histocompatibility complex (MHC) class II alleles or shared amino acid sequences.
Sera from 394 SLE patients were studied for anti-P using an enzyme-linked immunosorbent assay, and MHC class II alleles (HLA-DRB1, DQA1, and DQB1) were determined by DNA oligotyping.
Anti-P antibodies were found in 13-20% of patients in the majority of ethnic groups, but were perhaps more frequent in Chinese patients (36%) and less common in Bulgarian patients (6%). Neuropsychiatric lupus (psychosis and/or depression) was significantly associated with anti-P. The HLA-DR2, DQ6 haplotypes DRB11501 or 1503, DQA10102, and DQB10602 were increased in anti-P-positive whites, blacks, and Mexican Americans. The HLA-DQB10602 allele showed the strongest association with anti-P when these 3 ethnic groups were combined and compared with both race-matched anti-P-negative SLE patients and normal controls. The HLA-DQ8 specificity (DQB10302) was increased both in whites and in Mexican-Americans with anti-P who were negative for HLA-DQB10602, and perhaps also increased in Greeks, but not in blacks, in whom HLA-DQB10301 was increased. A shared amino acid sequence in HLA-DQB1 (at position 26 of leucine and position 30 of tyrosine) was strongly associated with anti-P positivity (70%) versus anti-P negativity (42%) across ethnic lines.
The anti-P response in SLE patients, occurring in approximately 15% of patients, was strongly influenced by certain MHC class II alleles and was correlated with diffuse neuropsychiatric dysfunction.
确定在一个大型多民族系统性红斑狼疮(SLE)患者队列中抗核糖体P抗体(抗-P)的频率及其临床关联,并评估抗-P是否与任何主要组织相容性复合体(MHC)II类等位基因或共享氨基酸序列相关。
采用酶联免疫吸附试验研究了394例SLE患者血清中的抗-P,并通过DNA寡核苷酸分型法确定MHC II类等位基因(HLA-DRB1、DQA1和DQB1)。
在大多数种族群体中,13%-20%的患者发现有抗-P抗体,但在中国患者中可能更常见(36%),而在保加利亚患者中较少见(6%)。神经精神性狼疮(精神病和/或抑郁症)与抗-P显著相关。在抗-P阳性的白人、黑人和墨西哥裔美国人中,HLA-DR2、DQ6单倍型DRB11501或1503、DQA10102和DQB10602有所增加。当将这三个种族群体合并,并与种族匹配的抗-P阴性SLE患者和正常对照进行比较时,HLA-DQB10602等位基因与抗-P的关联最为显著。HLA-DQ8特异性(DQB10302)在HLA-DQB10602阴性的抗-P阳性白人和墨西哥裔美国人中均有所增加,在希腊人中可能也有所增加,但在黑人中未增加,黑人中增加的是HLA-DQB10301。HLA-DQB1中一个共享的氨基酸序列(亮氨酸第26位和酪氨酸第30位)与跨种族的抗-P阳性(70%)和抗-P阴性(42%)密切相关。
SLE患者中约15%出现的抗-P反应受某些MHC II类等位基因的强烈影响,并与弥漫性神经精神功能障碍相关。