McDonnell G V, Mawhinney H, Graham C A, Hawkins S A, Middleton D
Northern Ireland Regional Neurology Service, Royal Hospitals Trust, Belfast, UK.
J Neurol Sci. 1999 May 1;165(1):77-83. doi: 10.1016/s0022-510x(99)00084-2.
To investigate the HLA-DR associations in relapsing-remitting/secondary progressive multiple sclerosis (RR/SPMS) and primary progressive MS (PPMS). The HLA-DR2 allele (or its split, HLA-DRB1*15) is felt to be a risk factor for MS, rather than a genetic marker for the population of origin. Some studies have indicated a different HLA-DR antigen profile in PPMS patients compared with those having an initially relapsing-remitting course, only those with relapsing disease showing an increase in HLA-DR2. Association of PPMS with DR4 has been suggested. Several DR alleles have also been felt to influence the prognosis in MS.
Genomic DNA was prepared from peripheral blood of 202 RR/SPMS patients identified in a population-based prevalence study, 102 PPMS patients identified throughout Northern Ireland and 398 normal controls (Nor) matched for the postcode areas of those identified in the prevalence study. Samples were typed for the HLA-DR antigens using polymerase chain reaction (PCR) technology and sequence specific oligonucleotide probes (SSOP).
A high incidence of HLA-DRB115 was found in each MS group - PPMS (63.73%), RR/SPMS (66.83%) - compared with normals (32.41%), (PPMS vs. Nor, P<0.0001: RR/SPMS vs. Nor, P<0.0001). HLA-DRB104 occurred at a lower incidence in both MS groups compared with controls - RR/SPMS (22%), PPMS (30%), Nor (35%). Overall, highly significant differences existed across the full HLA-DR allele distribution (RR/SPMS vs. Nor, P<0.0001, df=12: PPMS vs. Nor, P=0.0007, df=12). No significant differences existed between PPMS and RR/SPMS (P=0.47, df=12), and the allele distributions in benign and aggressive MS were similar.
These data suggest that in this population, HLA-DRB1*15 is indeed associated with PPMS and that PPMS has a HLA-DR profile distinct from the normal population but not from those with an initially relapsing-remitting course. No single allele is associated with either a good or poor prognosis.
研究复发缓解型/继发进展型多发性硬化症（RR/SPMS）和原发进展型多发性硬化症（PPMS）与人类白细胞抗原DR（HLA-DR）的相关性。HLA-DR2等位基因（或其分裂形式，HLA-DRB1*15）被认为是多发性硬化症的一个风险因素，而非起源人群的遗传标记。一些研究表明，与最初为复发缓解病程的患者相比，PPMS患者的HLA-DR抗原谱有所不同，只有复发型疾病患者的HLA-DR2有所增加。有研究提示PPMS与DR4有关联。还有几种DR等位基因也被认为会影响多发性硬化症的预后。
从一项基于人群的患病率研究中确定的202例RR/SPMS患者、北爱尔兰各地确定的102例PPMS患者的外周血以及与患病率研究中确定患者邮政编码区域相匹配的398名正常对照者（Nor）的外周血中提取基因组DNA。使用聚合酶链反应（PCR）技术和序列特异性寡核苷酸探针（SSOP）对样本进行HLA-DR抗原分型。
与正常对照者（32.41%）相比，各多发性硬化症组中HLA-DRB115的发生率都很高——PPMS组为63.73%，RR/SPMS组为66.83%（PPMS组与正常对照者相比，P<0.0001；RR/SPMS组与正常对照者相比，P<0.0001）。与对照组相比，两个多发性硬化症组中HLA-DRB104的发生率较低——RR/SPMS组为22%，PPMS组为30%，正常对照者为35%。总体而言，在整个HLA-DR等位基因分布中存在高度显著差异（RR/SPMS组与正常对照者相比，P<0.0001，自由度=12；PPMS组与正常对照者相比，P=0.0007，自由度=12）。PPMS组与RR/SPMS组之间无显著差异（P=0.47，自由度=12），良性和侵袭性多发性硬化症的等位基因分布相似。
这些数据表明，在该人群中，HLA-DRB1*15确实与PPMS相关，且PPMS的HLA-DR谱与正常人群不同，但与最初为复发缓解病程的患者无异。没有单一等位基因与预后良好或不良相关。
