Abstract：
BACKGROUND: Pediatric-Onset Multiple Sclerosis (POMS) is considered a complex disease entity and several genetic, hormonal, and environmental factors have been associated with disease pathogenesis. Linkage studies in Caucasians have consistently suggested the human leukocyte antigen (HLA) polymorphisms, as the genetic locus most strongly linked to MS, with the HLA-DRB1*15:01 allele, being associated with both adult and pediatric MS patients. Here we aim to investigate the prevalence of the HLA-DRB1 alleles among a Hellenic POMS cohort and any possible associations with clinical and imaging disease features.
METHODS: 100 POMS patients fulfilling the IPMSSG criteria, 168 Adult-Onset MS (AOMS) patients, and 246 Healthy Controls (HCs) have been enrolled. HLA genotyping was performed with a standard low-resolution sequence-specific oligonucleotide (SSO) technique.
RESULTS: POMS patients display a significantly increased HLA-DRB1*03 frequency compared to both HCs [24% vs. 12.6%, OR [95%CI]: 2.19 (1.21-3.97), p=0.016) and AOMS (24% vs. 13.1%, OR [95%CI]: 2.1 (1.1-3.98), p=0.034] respectively. HLA-DRB1*03-carriers display reduced risk for brainstem lesion development (OR [CI 95%]:0.19 (0.06-0.65), p=0.011). A significantly lower frequency of HLA-DRB1*07 (4% vs 13.4%, OR (95% CI): 0.27 (0.09-0.78), p= 0.017) and HLA-DRB1*11 (37% vs 52%, OR [95% CI]: 0.54 (0.34-0.87), p= 0.016) was observed in POMS compared to HCs.
CONCLUSIONS: The HLA-DRB1*03 allele was associated with a higher risk for POMS, replicating our previous findings, and with a lower risk for brainstem lesion development, a common clinical and neuroimaging feature in POMS, while HLA-DRB1*07 and HLA-DRB1*11 display a protective role. These findings expand the existing knowledge of HLA associations and POMS.
METHODS: 100 POMS patients fulfilling the IPMSSG criteria, 168 Adult-Onset MS (AOMS) patients, and 246 Healthy Controls (HCs) have been enrolled. HLA genotyping was performed with a standard low-resolution sequence-specific oligonucleotide (SSO) technique.
RESULTS: POMS patients display a significantly increased HLA-DRB1*03 frequency compared to both HCs [24% vs. 12.6%, OR [95%CI]: 2.19 (1.21-3.97), p=0.016) and AOMS (24% vs. 13.1%, OR [95%CI]: 2.1 (1.1-3.98), p=0.034] respectively. HLA-DRB1*03-carriers display reduced risk for brainstem lesion development (OR [CI 95%]:0.19 (0.06-0.65), p=0.011). A significantly lower frequency of HLA-DRB1*07 (4% vs 13.4%, OR (95% CI): 0.27 (0.09-0.78), p= 0.017) and HLA-DRB1*11 (37% vs 52%, OR [95% CI]: 0.54 (0.34-0.87), p= 0.016) was observed in POMS compared to HCs.
CONCLUSIONS: The HLA-DRB1*03 allele was associated with a higher risk for POMS, replicating our previous findings, and with a lower risk for brainstem lesion development, a common clinical and neuroimaging feature in POMS, while HLA-DRB1*07 and HLA-DRB1*11 display a protective role. These findings expand the existing knowledge of HLA associations and POMS.
摘要：
背景：小儿型多发性硬化症（POMS）被认为是一种复杂的疾病实体，荷尔蒙，环境因素与疾病的发病机制有关。高加索人的连锁研究一直表明人类白细胞抗原（HLA）多态性，作为与MS最密切相关的遗传基因，HLA-DRB1*15:01等位基因，与成人和儿童MS患者有关。在这里，我们旨在调查HLA-DRB1等位基因在希腊POMS队列中的患病率以及与临床和影像学疾病特征的任何可能关联。
方法：100名符合IPMSSG标准的POMS患者，168名成人发作的MS（AOMS）患者，并纳入了246名健康对照（HC）。用标准低分辨率序列特异性寡核苷酸(SSO)技术进行HLA基因分型。
结果：与两种HC相比，POMS患者的HLA-DRB1*03频率显着增加[24％vs.12.6%,或[95CI]：2.19（1.21-3.97），p=0.016）和AOMS（24%与13.1%,或[95CI]：2.1（1.1-3.98），分别为p=0.034]。HLA-DRB1*03携带者显示脑干病变发展的风险降低(OR[CI95%]:0.19(0.06-0.65),p=0.011)。HLA-DRB1*07的频率明显降低(4%vs13.4%，OR（95%CI）：0.27（0.09-0.78），p=0.017)和HLA-DRB1*11(37%对52%，或[95%CI]：0.54（0.34-0.87），与HC相比，在POMS中观察到p=0.016）。
结论：HLA-DRB1*03等位基因与POMS的高风险相关，复制我们之前的发现,脑干病变发展的风险较低，POMS中常见的临床和神经影像学特征，而HLA-DRB1*07和HLA-DRB1*11显示保护作用。这些发现扩展了HLA关联和POMS的现有知识。
方法：100名符合IPMSSG标准的POMS患者，168名成人发作的MS（AOMS）患者，并纳入了246名健康对照（HC）。用标准低分辨率序列特异性寡核苷酸(SSO)技术进行HLA基因分型。
结果：与两种HC相比，POMS患者的HLA-DRB1*03频率显着增加[24％vs.12.6%,或[95CI]：2.19（1.21-3.97），p=0.016）和AOMS（24%与13.1%,或[95CI]：2.1（1.1-3.98），分别为p=0.034]。HLA-DRB1*03携带者显示脑干病变发展的风险降低(OR[CI95%]:0.19(0.06-0.65),p=0.011)。HLA-DRB1*07的频率明显降低(4%vs13.4%，OR（95%CI）：0.27（0.09-0.78），p=0.017)和HLA-DRB1*11(37%对52%，或[95%CI]：0.54（0.34-0.87），与HC相比，在POMS中观察到p=0.016）。
结论：HLA-DRB1*03等位基因与POMS的高风险相关，复制我们之前的发现,脑干病变发展的风险较低，POMS中常见的临床和神经影像学特征，而HLA-DRB1*07和HLA-DRB1*11显示保护作用。这些发现扩展了HLA关联和POMS的现有知识。
