Medical Research Group (GINUMED) University Corporation Rafael Nuñez, Immunology Department, Faculty of medicine. Cartagena, Colombia; Group of Clinical and Experimental Allergy (GACE), IPS Universitaria, University of Antioquia. Medellín, Colombia.
Group of Clinical and Experimental Allergy (GACE), IPS Universitaria, University of Antioquia. Medellín, Colombia.
Immunol Lett. 2020 Apr;220:71-78. doi: 10.1016/j.imlet.2020.02.003. Epub 2020 Feb 3.
Human proteins such as interleukin-24 (IL24), thyroperoxidase (TPO) and thyroglobulin (Tg) are targets of IgE or IgG autoantibodies. Why these proteins are recognized by autoantibodies in some patients with chronic spontaneous urticaria (CSU) or hypothyroidism is unknown.
Through in silico analysis, identify antigen patches of TPO, Tg and IL24 and compare the sequences of these human proteins with some prevalent allergens.
The amino acids sequences of IL24, thyroperoxidase and thyroglobulin were compared between them and with 22 environmental allergens. Phylogenetic studies and multiple pairing were carried out to explore the degree of protein identity and cover. The proteins without 3D structure reported in the database, were modeled by homology with "Swiss Modeller" and compared through PYMOL. Residues conserved and accessible to the solvent (rASA> 0.25) were located in the 3D model to identify possible areas of cross-reactivity and antigen binding.
We build a 3D model of the TPO and thyroglobulin protein base on proteins closely related. Five epitopes for TPO, six for IL24 and six for thyroglobulin were predicted. The amino acid sequences of allergens from different sources (Dermatophagoides pteronyssinus, Blomia tropicalis, Betula verrucosa, Cynodon dactylon, Aspergillus fumigatus, Canis domesticus, Felis domesticus) were compared with human TPO, Tg and IL24. The cover and alignments between allergens and human proteins were low.
We identify possible linear and conformational epitopes of TPO, Tg and IL24 that could be the target of IgE or IgG binding in patients with urticaria or hypothyroidism; These epitopes do not appear to be present among common environmental allergens, suggesting that autoreactivity to these human proteins are not by cross-reactivity.
白细胞介素 24（IL24）、甲状腺过氧化物酶（TPO）和甲状腺球蛋白（Tg）等人类蛋白是 IgE 或 IgG 自身抗体的靶标。为什么在一些患有慢性自发性荨麻疹（CSU）或甲状腺功能减退症的患者中，这些蛋白会被自身抗体识别，目前尚不清楚。
通过计算机分析，确定 TPO、Tg 和 IL24 的抗原表位，并比较这些人类蛋白的序列与一些常见过敏原的序列。
比较了 IL24、甲状腺过氧化物酶和甲状腺球蛋白的氨基酸序列，并与 22 种环境过敏原进行了比较。进行了系统发育研究和多次配对，以探索蛋白质同一性和覆盖率的程度。数据库中未报告具有 3D 结构的蛋白质，使用“Swiss Modeler”进行同源建模，并通过 PYMOL 进行比较。定位了数据库中报告的没有 3D 结构的蛋白质的保守和可及溶剂的残基（rASA>0.25），以识别可能的交叉反应和抗原结合区域。
我们基于密切相关的蛋白质构建了 TPO 和甲状腺球蛋白蛋白的 3D 模型。预测了 TPO 的 5 个表位、IL24 的 6 个表位和 Tg 的 6 个表位。比较了来自不同来源的过敏原（屋尘螨、热带无爪螨、桦树花粉、狗牙根、烟曲霉、犬、猫）与人类 TPO、Tg 和 IL24 的氨基酸序列。过敏原与人类蛋白之间的覆盖率和比对都较低。
我们确定了 TPO、Tg 和 IL24 的可能线性和构象表位，这些表位可能是荨麻疹或甲状腺功能减退症患者中 IgE 或 IgG 结合的靶标；这些表位似乎不存在于常见的环境过敏原中，这表明这些人类蛋白的自身反应性不是通过交叉反应产生的。
