Anti-Ephrin Type-B Receptor 2 (EphB2) and Anti-Three Prime Histone mRNA EXonuclease 1 (THEX1) Autoantibodies in Scleroderma and Lupus.
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.
INSERM UMRs 1097, Parc Scientifique de Luminy, Marseille, France.|Aix Marseille Université, Marseille, France.
Doua F
DF
Azzouz
INSERM UMRs 1097, Parc Scientifique de Luminy, Marseille, France.|Aix Marseille Université, Marseille, France.
Gabriel V
GV
Martin
INSERM UMRs 1097, Parc Scientifique de Luminy, Marseille, France.|Aix Marseille Université, Marseille, France.
Fanny
F
Arnoux
INSERM UMRs 1097, Parc Scientifique de Luminy, Marseille, France.|Rhumatologie, IML, AP-HM, Hôpital Sainte Marguerite, Marseille, France.
Nathalie
N
Balandraud
Service d'Immunologie Clinique, Hôpitaux universitaires de Strasbourg, Strasbourg, France.|UPR CNRS 3572, Strasbourg, France.
Thierry
T
Martin
Institut d'Immunologie Centre Hospitalier Régional et Universitaire de Lille, Lille, France.|EA 2686, Université de Lille, Lille, France.
Sylvain
S
Dubucquoi
Service de Médecine Interne, Centre National de Référence de la Sclérodermie Systémique, Hôpital Claude Huriez, Lille, France.
Eric
E
Hachulla
Service de Médecine Interne et Pathologie Vasculaire, Hôpital St Louis, Paris, France.|INSERM U697, Hôpital St Louis, Paris, France.
Dominique
D
Farge-Bancel
Service de Médecine Interne, Hôpital St Antoine, Paris, France.
Kiet
K
Tiev
Service de Médecine Interne, Hôpital St Antoine, Paris, France.
Jean
J
Cabane
UMR-S 1076 Endothélium, Pathologies Vasculaires et Cibles Thérapeutiques - Faculté de Pharmacie, Marseille, France.
Nathalie
N
Bardin
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.
Laurent
L
Chiche
INSERM UMRs 1097, Parc Scientifique de Luminy, Marseille, France.|Aix Marseille Université, Marseille, France.
Marielle
M
Martin
INSERM UMRs 1097, Parc Scientifique de Luminy, Marseille, France.|Aix Marseille Université, Marseille, France.
Eléonore C
EC
Caillet
INSERM UMRs 1097, Parc Scientifique de Luminy, Marseille, France.|Aix Marseille Université, Marseille, France.
Sami B
SB
Kanaan
AP-HM, Pôle de Médecine Interne, Centre de Compétence PACA Ouest pour la prise en charge des maladies auto-immunes systémiques, Marseille, France.
Jean Robert
JR
Harlé
Aix Marseille Université, Marseille, 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.
Brigitte
B
Granel
Service de Médecine Interne, CHU Bretonneau, Tours, France.
Elisabeth
E
Diot
INSERM UMRs 1097, Parc Scientifique de Luminy, Marseille, France.|Rhumatologie, IML, AP-HM, Hôpital Sainte Marguerite, Marseille, France.
Jean
J
Roudier
INSERM UMRs 1097, Parc Scientifique de Luminy, Marseille, France.|Rhumatologie, IML, AP-HM, Hôpital Sainte Marguerite, Marseille, France.
Isabelle
I
Auger
INSERM UMRs 1097, Parc Scientifique de Luminy, Marseille, France.|Aix Marseille Université, Marseille, France.
Nathalie C
NC
Lambert
D001323:Autoantibodies / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D018604:Epitope Mapping; D005095:Exoribonucleases / Q000276:immunology*; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000175:diagnosis / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D036183:Receptor, EphB2 / Q000276:immunology*; D012595:Scleroderma, Systemic / Q000276:immunology*; D012680:Sensitivity and Specificity
D001323:Autoantibodies; C586310:EPHB2 protein, human; D036183:Receptor, EphB2; C482201:ERI1 protein, human; D005095:Exoribonucleases