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Perspective ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Immunol. | doi: 10.3389/fimmu.2019.00035

Ankylosing Spondylitis: a trade off of HLA-B27, ERAP and pathogen interconnections? Focus on Sardinia

  • 1Sapienza University of Rome, Italy
  • 2Azienda Ospedaliero-Universitaria Cagliari, Italy

Abstract
The frequency of HLA-B27 in patients with Ankylosing Spondylitis (AS) is over 85%. There are more than 170 recognized HLA-B27 alleles but the majority of them is not sufficiently represented for disease-association studies. So far only two alleles, the HLA-B*2706 in Asia and the HLA-B*2709 in Sardinia, have not been found to confer susceptibility to AS. The highly homogenous genetic structure of the Sardinian population has favoured the search of relevant variants for such studies. Moreover, malaria, once endemic in the island, has been shown to have contributed to shape the genome of the native population affecting the frequency of relevant alleles. In Sardinia, the prevalence of HLA-B*2709, which differs from the strongly AS-associated B*2705 prototype for one amino acid (His/Asp116) in the F pocket of the peptide binding groove, is around 20% of all HLA-B27 alleles. We have previously hypothesized that malaria could have contributed to the establishment of this allele in Sardinia. Based on our recent findings, in this perspective article we speculate that the Endoplasmic Reticulum AminoPeptidases, ERAP1 and 2, associated with AS and involved in antigen presentation, underwent co-selection by malaria. These genes, besides shaping the immunopeptidome of HLA-class I molecules, have other biological functions that could also be involved in the immunosurveillance against malaria.

Keywords: HLA-B27 alleles, ankylosing spondylitis, ERAP1 and 2, Autoimmunity, Malaria

Received: 05 Nov 2018; Accepted: 08 Jan 2019.

Edited by:

Philippe Saas, INSERM U1098 Interactions Hôte-Greffon-Tumeur & Ingénierie Cellulaire et Génique, France

Reviewed by:

Efstratios Stratikos, National Centre of Scientific Research Demokritos, Greece
Xenofon Baraliakos, Rheumazentrum Ruhrgebiet, Germany  

Copyright: © 2019 Paladini, Fiorillo, Tedeschi, Cauli, Mathieu and Sorrentino. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Rosa Sorrentino, Sapienza University of Rome, Rome, Italy, rosa.sorrentino@uniroma1.it