Sandberg-Wollheim M, Ciusani E, Salmaggi A, Pociot F
Department of Neurology, Lund University Hospital, Sweden.
Mult Scler. 1995 Nov;1(3):181-5. doi: 10.1177/135245859500100309.
We have analyzed the distribution of tumor necrosis factor (TNF) a and -b microsatellite alleles in HLA-DQ and -DR typed Swedish patients with multiple sclerosis (MS) (n = 122) and ethnically matched control subjects (n = 178). We found significant differences in the frequencies of TNFa and TNFb alleles between patients and controls. TNFaII was significantly associated with MS. This was also the case for the combination of TNFaII with TNFb4. However, TNFaII (alone or in combination with TNFb4) did not show any disease association independent of DQA10102/ DQB10602/DR2, whereas the previously reported strong association with HLA-DQA10102/DQB10602/DR2 in Scandinavian populations was confirmed. Therefore the association of TNFaII (and TNFb4) is most likely secondary to the increase of DQA10102/DQB10602/DR2 in MS patients. The proportion of TNFa6 positive individuals was lower among DR2-negative MS patients than among DR2-negative controls (P = 0.08). Since the presence of the TNFa6 allele correlates with low TNF alpha production in response to lipopolysaccharide, it could be speculated that DR2-negative MS patients have an increased risk of being high TNF alpha producers in response to exogenous stimuli.
我们分析了肿瘤坏死因子（TNF）α和β微卫星等位基因在HLA - DQ和 - DR分型的瑞典多发性硬化症（MS）患者（n = 122）以及种族匹配的对照受试者（n = 178）中的分布情况。我们发现患者和对照之间TNFα和TNFβ等位基因频率存在显著差异。TNFαII与MS显著相关。TNFαII与TNFβ4的组合情况也是如此。然而，TNFαII（单独或与TNFβ4组合）在不依赖DQA10102 / DQB10602 / DR2的情况下未显示出任何疾病关联，而此前报道的斯堪的纳维亚人群中与HLA - DQA10102 / DQB10602 / DR2的强关联得到了证实。因此，TNFαII（和TNFβ4）的关联很可能是MS患者中DQA10102 / DQB10602 / DR2增加的继发结果。DR2阴性的MS患者中TNFα6阳性个体的比例低于DR2阴性对照（P = 0.08）。由于TNFα6等位基因的存在与脂多糖刺激后低TNFα产生相关，可以推测DR2阴性的MS患者对外源性刺激产生高TNFα的风险增加。
