PRIMARILY CHRONIC PROGRESSIVE AND RELAPSING REMITTING MULTIPLE-SCLEROSIS - 2 IMMUNOGENETICALLY DISTINCT DISEASE ENTITIES
PRIMARILY CHRONIC PROGRESSIVE AND RELAPSING REMITTING MULTIPLE-SCLEROSIS - 2 IMMUNOGENETICALLY DISTINCT DISEASE ENTITIES
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DOI：
10.1073/pnas.86.18.7113
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发表时间：
1989-09-01
影响因子：
11.1
通讯作者：
WALLIN, J
中科院分区：
文献类型：
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作者：
OLERUP, O;HILLERT, J;WALLIN, J
应用DRB、DQA和DQB cDNA探针对100例临床确诊的多发性硬化（MS）患者进行了限制性片段长度多态性分析。26例患者主要为慢性进展型MS，74例为复发/缓解型MS。后一组包括继发性症状进展的患者。发现MS的两种临床形式均与DRw 15、DQw 6单倍型相关。此外，原发性慢性进行性MS与DR 4、DQw 8、DR 7、DQw 9和DRw 8、DQw 4单倍型中观察到的DQB 1限制性片段模式正相关，以及与对应于血清学特异性DQw 7的Taq I DQB 1等位基因模式负相关。复发/缓解型MS与DRw 17、DQw 2单倍型中观察到的DQB 1等位基因模式呈正相关。这3个DQB 1等位基因与DRw 15基因呈强负连锁不平衡。每种临床形式的MS的两种易感性标志物在确定遗传易感性方面起相加作用，因为携带两种标志物的个体的相对风险大致等于各自风险的总和。DQB 1基因座的限制性片段长度多态性定义的不同等位基因有助于易感性和耐药，主要是慢性进行性MS以及复发/缓解MS的易感性。观察到的免疫遗传异质性MS的不同临床形式之间的支持的假设，主要是慢性进行性MS和复发/缓解MS是两个不同的疾病实体。
HLA class II gene polymorphism was investigated in 100 patients with clinically definite multiple sclerosis (MS) by restriction fragment length polymorphism analysis of Taq I-digested DNA using DRB, DQA, and DQB cDNA probes. Twenty-six patients had primarily chronic progressive MS and 74 had relapsing/remitting MS. The latter group included patients with a secondary progressie evolution of symptoms. Both clinical forms of MS were found to be associated with the DRw15, DQw6 haplotype. In addition, primarily chronic progressive MS was positively associated with the DQB1 restriction fragment pattern seen in DR4, DQw8, DR7, DQw9, and DRw8, DQw4 haplotypes, as well as negatively associated with the Taq I DQB1 allelic pattern corresponding to the serological specificity DQw7. Relapsing/remitting MS was positively associated with the DQB1 allelic pattern observed in the DRw17,DQw2 haplotype. These three DQB1 alleles are in strong negative linkage disequilibria with DRw15. The two susceptibility markers of each clinical form of MS act additively in determining the genetic susceptibility, as the relative risks for individuals carrying both markers roughly equal the sum of respective risks. Different alleles of the DQB1 locus defined by restriction fragment length polymorphisms contribute to susceptibility and resistance to primarily chronic progressive MS as well as to susceptibility to relapsing/remitting MS. The observed immunogenetic heterogeneity between the different clinical forms of MS favors the hypothesis that primarily chronic progressive MS and relapsing/remitting MS are two distinct disease entities.