Derdelinckx Judith, Nkansah Irene, Ooms Naomi, Van Bruggen Laura, Emonds Marie-Paule, Daniëls Liesbeth, Reynders Tatjana, Willekens Barbara, Cras Patrick, Berneman Zwi N, Cools Nathalie
Laboratory of Experimental Hematology, Vaccine and Infectious Disease Institute (VaxInfectio), Faculty of Medicine and Health Sciences, University of Antwerp, 2610 Antwerp, Belgium.
Division of Neurology, Antwerp University Hospital, 2650 Edegem, Belgium.
Cells. 2020 Dec 17;9(12):2703. doi: 10.3390/cells9122703.
When aiming to restore myelin tolerance using antigen-specific treatment approaches in MS, the wide variety of myelin-derived antigens towards which immune responses are targeted in multiple sclerosis (MS) patients needs to be taken into account. Uncertainty remains as to whether the myelin reactivity pattern of a specific MS patient can be predicted based upon the human leukocyte antigen (HLA) class II haplotype of the patient.
In this study, we analyzed the reactivity towards myelin oligodendrocyte glycoprotein (MOG), myelin basic protein (MBP) and proteolipid protein (PLP) peptides using direct interferon (IFN)-γ enzyme-linked immune absorbent spot (ELISPOT). Next, the HLA class II haplotype profile was determined by next-generation sequencing. In doing so, we aimed to evaluate the possible association between the precursor frequency of myelin-reactive T cells and the HLA haplotype.
Reactivity towards any of the analyzed peptides could be demonstrated in 65.0% (13/20) of MS patients and in 60.0% (6/10) of healthy controls. At least one of the MS risk alleles HLA-DRB115:01, HLA-DQA101:02 and HLA-DQB1*06:02 was found in 70.0% (14/20) of patients and in 20.0% (2/10) of healthy controls. No difference in the presence of a myelin-specific response, nor in the frequency of myelin peptide-reactive precursor cells could be detected among carriers and non-carriers of these risk alleles.
No association between HLA haplotype and myelin reactivity profile was present in our study population. This complicates the development of antigen-specific treatment approaches and implies the need for multi-epitope targeting in an HLA-unrestricted manner to fully address the wide variation in myelin responses and HLA profiles in a heterogeneous group of MS patients.
当旨在使用抗原特异性治疗方法在多发性硬化症（MS）中恢复髓鞘耐受性时，需要考虑多发性硬化症（MS）患者针对其产生免疫反应的多种髓鞘衍生抗原。关于是否可以根据患者的人类白细胞抗原（HLA）II类单倍型预测特定MS患者的髓鞘反应模式仍存在不确定性。
在本研究中，我们使用直接干扰素（IFN）-γ酶联免疫斑点法（ELISPOT）分析了对髓鞘少突胶质细胞糖蛋白（MOG）、髓鞘碱性蛋白（MBP）和蛋白脂蛋白（PLP）肽的反应性。接下来，通过下一代测序确定HLA II类单倍型谱。通过这样做，我们旨在评估髓鞘反应性T细胞的前体频率与HLA单倍型之间的可能关联。
65.0%（13/20）的MS患者和60.0%（6/10）的健康对照者对任何一种分析的肽都有反应性。70.0%（14/20）的患者和20.0%（2/10）的健康对照者中发现了至少一种MS风险等位基因HLA-DRB115:01、HLA-DQA101:02和HLA-DQB1*06:02。在这些风险等位基因的携带者和非携带者之间，未检测到髓鞘特异性反应的存在或髓鞘肽反应性前体细胞频率的差异。
在我们的研究人群中，HLA单倍型与髓鞘反应性谱之间不存在关联。这使得抗原特异性治疗方法的开发变得复杂，并意味着需要以HLA无限制的方式靶向多表位，以充分解决异质性MS患者群体中髓鞘反应和HLA谱的广泛差异。
