Mimetismo molecular entre peroxidasa tiroidea humana, tiroglobulina, peroxidasa de eosinófilos, IL-24 y antígenos de microorganismos

Abstract

Molecular mimicry among human thyroid peroxidase, thyroglobulin, eosinophil peroxidase, IL-24, and microorganism antigens.

Sánchez, A. a,b, García, V.a, Emiliani, Y. a, Sánchez, J. b, Ramos, J. a González, Sa. Munera, M. a

a. Health Faculty, Medical Research Group (GINUMED), University Corporation Rafael Nuñez, Cartagena, Colombia
b. Group of Clinical and Experimental Allergy (GACE), IPS Universitaria, University of Antioquia, Medellín, Colombia

Keywords: Autoimmune Diseases, Molecular Mimicry, Urticaria, Thyroid Disease.

Introduction:

Molecular mimicry has been described between human antigens and microorganism proteins. These mechanisms can induce cross-reactivity processes that favor the development of autoimmune diseases such as chronic urticaria and some thyroid diseases. Human thyroid peroxidase (TPO) is one of the main antigens in thyroid diseases. It has been shown that this hormone is associated with spontaneous chronic urticaria. In other in silico studies, epitopes of TPO, thyroglobulin, and IL-24 have been identified as targets for IgE or IgG binding in patients with urticaria or hypothyroidism.

Objective: Identify molecular mimicry between TPO, eosinophil peroxidase (EPX), thyroglobulin, IL-24, and microorganism antigens.

Methodology:
Through in silico analysis, we performed local alignments between human antigens and microorganism antigens using PSI-BLAST. Proteins without a 3D structure were modeled by homology using the Swiss Modeller server, and epitope prediction was performed using Ellipro. Epitopes were located in the 3D models using PYMOL software.

Results:
A total of 38 microorganism antigens (parasites, bacteria) had identities between 30% and 45%, with the highest being with Anisakis simplex. The alignment between two candidate proteins of A. simplex and EPX showed significant values, with identities of 43% and 44%. In bacteria, Campylobacter jejuni showed the highest identity with thyroglobulin (35%). We predicted 220 linear and conformational epitopes of microorganism antigens. Proteins similar to peroxidasin from Toxocara canis and Trichinella pseudospiralis showed 10 epitopes similar to TPO and EPX, as possible molecules triggering cross-reactivity. No virus showed identity with the studied human proteins.

Conclusion:
TPO and EPX antigens shared potential cross-reactive epitopes with bacterial proteins and nematodes, suggesting that molecular mimicry could be a mechanism explaining the relationship between infections and urticaria/hypothyroidism.