Anti-Ephrin Type-B Receptor 2 (EphB2) and Anti-Three Prime Histone mRNA EXonuclease 1 (THEX1) Autoantibodies in Scleroderma and Lupus.
Fiche publication
Date publication
janvier 2016
Journal
PloS one
Auteurs
Membres identifiés du Cancéropôle Est :
Pr MARTIN Thierry
Tous les auteurs :
Azzouz DF, Martin GV, Arnoux F, Balandraud N, Martin T, Dubucquoi S, Hachulla E, Farge-Bancel D, Tiev K, Cabane J, Bardin N, Chiche L, Martin M, Caillet EC, Kanaan SB, Harlé JR, Granel B, Diot E, Roudier J, Auger I, Lambert NC
Lien Pubmed
Résumé
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.
Mots clés
Autoantibodies, blood, Enzyme-Linked Immunosorbent Assay, Epitope Mapping, Exoribonucleases, immunology, Female, Humans, Lupus Erythematosus, Systemic, diagnosis, Male, Middle Aged, Receptor, EphB2, immunology, Scleroderma, Systemic, immunology, Sensitivity and Specificity
Référence
PLoS ONE. 2016 ;11(9):e0160283