The impact of HLA-DRB1 alleles in a Hellenic, Pediatric-Onset Multiple Sclerosis cohort: Implications on clinical and neuroimaging profile.

IF 2.7 4区医学 Q2 CLINICAL NEUROLOGY

Neurological Sciences Pub Date : 2024-11-01 Epub Date: 2024-05-31 DOI:10.1007/s10072-024-07619-0

Charalampos Skarlis, Nikolaos Markoglou, Maria Gontika, Artemios Artemiadis, Maria-Roser Pons, Leonidas Stefanis, Marinos Dalakas, George Chrousos, Maria Anagnostouli

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引用次数: 0

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.

Materials and 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.

Conclusion: 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.

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希腊小儿多发性硬化症队列中 HLA-DRB1 等位基因的影响：对临床和神经影像学特征的影响。

背景：小儿多发性硬化症（POMS）被认为是一种复杂的疾病，多种遗传、激素和环境因素与疾病的发病机制有关。在白种人中进行的连锁研究一致表明，人类白细胞抗原（HLA）多态性是与多发性硬化症关系最密切的遗传位点，其中 HLA-DRB1*15:01 等位基因与成人和儿童多发性硬化症患者均有关联。在此，我们旨在调查希腊 POMS 队列中 HLA-DRB1 等位基因的患病率以及与临床和影像学疾病特征之间可能存在的关联。采用标准低分辨率序列特异性寡核苷酸（SSO）技术进行了HLA基因分型：结果：与HC（24% vs. 12.6%，OR [95%CI]：2.19 (1.21-3.97)，p=0.016）和AOMS（24% vs. 13.1%，OR [95%CI]：2.1 (1.1-3.98)，p=0.034）相比，POMS患者的HLA-DRB1*03频率明显增加。HLA-DRB1*03携带者发生脑干病变的风险较低（OR [CI 95%]：0.19 (0.06-0.65)，p=0.011）。HLA-DRB1*07（4% vs 13.4%，OR [CI 95%]：0.27 (0.09-0.78)，p= 0.017）和 HLA-DRB1*11 （37% vs 52%，OR [CI 95%]：0.54 (0.34-0.78) ，p= 0.017）的频率明显较低：结论：与HCs相比，在POMS中观察到HLA-DRB1*11（37% vs 52%，OR [95% CI]：0.54 (0.34-0.87)，p= 0.016）：结论：HLA-DRB1*03等位基因与较高的POMS风险相关，这与我们之前的研究结果相同，并且与较低的脑干病变发生风险相关，而脑干病变是POMS常见的临床和神经影像学特征，而HLA-DRB1*07和HLA-DRB1*11则具有保护作用。这些发现扩展了现有的关于HLA与POMS关联的知识。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Neurological Sciences 医学-临床神经学

CiteScore

6.10

自引率

3.00%

发文量

743

审稿时长

4 months

期刊介绍： Neurological Sciences is intended to provide a medium for the communication of results and ideas in the field of neuroscience. The journal welcomes contributions in both the basic and clinical aspects of the neurosciences. The official language of the journal is English. Reports are published in the form of original articles, short communications, editorials, reviews and letters to the editor. Original articles present the results of experimental or clinical studies in the neurosciences, while short communications are succinct reports permitting the rapid publication of novel results. Original contributions may be submitted for the special sections History of Neurology, Health Care and Neurological Digressions - a forum for cultural topics related to the neurosciences. The journal also publishes correspondence book reviews, meeting reports and announcements.