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PLoS One. 2016 Sep 12;11(9):e0160283. doi: 10.1371/journal.pone.0160283. eCollection 2016.

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

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INSERM UMRs 1097, Parc Scientifique de Luminy, Marseille, France.
Aix Marseille Université, Marseille, France.
Rhumatologie, IML, AP-HM, Hôpital Sainte Marguerite, Marseille, France.
Service d'Immunologie Clinique, Hôpitaux universitaires de Strasbourg, Strasbourg, France.
UPR CNRS 3572, Strasbourg, France.
Institut d'Immunologie Centre Hospitalier Régional et Universitaire de Lille, Lille, France.
EA 2686, Université de Lille, Lille, France.
Service de Médecine Interne, Centre National de Référence de la Sclérodermie Systémique, Hôpital Claude Huriez, Lille, France.
Service de Médecine Interne et Pathologie Vasculaire, Hôpital St Louis, Paris, France.
INSERM U697, Hôpital St Louis, Paris, France.
Service de Médecine Interne, Hôpital St Antoine, Paris, France.
UMR-S 1076 Endothélium, Pathologies Vasculaires et Cibles Thérapeutiques - Faculté de Pharmacie, Marseille, France.
AP-HM, Pôle de Médecine Interne, Centre de Compétence PACA Ouest pour la prise en charge des maladies auto-immunes systémiques, Marseille, France.
Aix-Marseille Université, Centre d'Immunologie de Marseille-Luminy (CIML), INSERM, CNRS UMR7280, Marseille, France.
Service de Médecine Interne, CHU Bretonneau, Tours, 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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