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Identification of antigenic epitopes of thyroperoxidase, thyroglobulin and interleukin-24. Exploration of cross-reactivity with environmental allergens and possible role in urticaria and hypothyroidism.
Immunology Letters ( IF 3.3 ) Pub Date : 2020-02-03 , DOI: 10.1016/j.imlet.2020.02.003
Andrés Sánchez 1 , Ricardo Cardona 2 , Marlon Munera 3 , Jorge Sánchez 2
Affiliation  

BACKGROUND 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. OBJECTIVE Through in silico analysis, identify antigen patches of TPO, Tg and IL24 and compare the sequences of these human proteins with some prevalent allergens. METHODS 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. RESULTS 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. CONCLUSION 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.

中文翻译:

鉴定甲状腺过氧化物酶,甲状腺球蛋白和白介素24的抗原表位。探索与环境过敏原的交叉反应性,以及在荨麻疹和甲状腺功能减退中的可能作用。

背景技术诸如白介素24(IL24),甲状腺过氧化物酶(TPO)和甲状腺球蛋白(Tg)的人类蛋白质是IgE或IgG自身抗体的靶标。在某些慢性自发性荨麻疹(CSU)或甲状腺功能低下的患者中,为什么这些蛋白会被自身抗体识别。目的通过计算机分析,鉴定TPO,Tg和IL24的抗原斑块,并将这些人蛋白质的序列与一些普遍的过敏原进行比较。方法将IL24,甲状腺过氧化物酶和甲状腺球蛋白的氨基酸序列与22种环境变应原进行比较。进行了系统进化研究和多次配对,以探索蛋白质同一性和覆盖度的程度。数据库中报告的无3D结构的蛋白质通过与“ Swiss Modeller”的同源性建模,并通过PYMOL进行比较。在3D模型中定位了溶剂保守且可接近的残基(rASA> 0.25),以识别交叉反应和抗原结合的可能区域。结果我们基于紧密相关的蛋白质建立了TPO和甲状腺球蛋白的3D模型。预测到TPO有5个表位,IL24有6个表位,甲状腺球蛋白有6个表位。比较了来自不同来源的过敏原​​的氨基酸序列(Dermatophagoides pteronyssinus,Blomiatropicis,Betula verrucosa,Cynodon dactylon,Aspergillus fumigatus,Canis domesticus,Felis domesticus)与人TPO,Tg和IL24的比较。变应原和人类蛋白质之间的覆盖率和排列率很低。结论我们确定了荨麻疹或甲状腺功能减退症患者可能存在的TPO,Tg和IL24线性和构象表位可能是IgE或IgG结合的目标。
更新日期:2020-02-03
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