Anti-Ephrin Type-B Receptor 2 (EphB2) and Anti-Three Prime Histone mRNA EXonuclease 1 (THEX1) Autoantibodies in Scleroderma and Lupus.

Authors:
Doua F Azzouz
Doua F Azzouz
Centre Hospitalo-Universitaire de Nice
France
Gabriel V Martin
Gabriel V Martin
INSERM UMRs 1097
Fanny Arnoux
Fanny Arnoux
Aix Marseille Université
France
Nathalie Balandraud
Nathalie Balandraud
France; Laboratoire d'immunogénétique
Thierry Martin
Thierry Martin
Hôpitaux Universitaires de Strasbourg
France
Sylvain Dubucquoi
Sylvain Dubucquoi
Universite' Lille Nord de France;
France
Eric Hachulla
Eric Hachulla
Université Paris Descartes
France
Dominique Farge-Bancel
Dominique Farge-Bancel
Saint Louis Hospital
France

PLoS One 2016 12;11(9):e0160283. Epub 2016 Sep 12.

INSERM UMRs 1097, Parc Scientifique de Luminy, Marseille, France.

In a pilot ProtoArray analysis, we identified 6 proteins out of 9483 recognized by autoantibodies (AAb) from patients with systemic sclerosis (SSc). We further investigated the 6 candidates by ELISA on hundreds of controls and patients, including patients with Systemic Lupus Erythematosus (SLE), known for high sera reactivity and overlapping AAb with SSc. Only 2 of the 6 candidates, Ephrin type-B receptor 2 (EphB2) and Three prime Histone mRNA EXonuclease 1 (THEX1), remained significantly recognized by sera samples from SSc compared to controls (healthy or with rheumatic diseases) with, respectively, 34% versus 14% (P = 2.10-4) and 60% versus 28% (P = 3.10-8). Above all, EphB2 and THEX1 revealed to be mainly recognized by SLE sera samples with respectively 56%, (P = 2.10-10) and 82% (P = 5.10-13). As anti-EphB2 and anti-THEX1 AAb were found in both diseases, an epitope mapping was realized on each protein to refine SSc and SLE diagnosis. A 15-mer peptide from EphB2 allowed to identify 35% of SLE sera samples (N = 48) versus only 5% of any other sera samples (N = 157), including SSc sera samples. AAb titers were significantly higher in SLE sera (P<0.0001) and correlated with disease activity (p<0.02). We could not find an epitope on EphB2 protein for SSc neither on THEX1 for SSc or SLE. We showed that patients with SSc or SLE have AAb against EphB2, a protein involved in angiogenesis, and THEX1, a 3'-5' exoribonuclease involved in histone mRNA degradation. We have further identified a peptide from EphB2 as a specific and sensitive tool for SLE diagnosis.

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0160283PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5019431PMC

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August 2017
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