Anti-endothelial cell antibodies from patients with limited cutaneous systemic sclerosis bind to centromeric protein B (CENP-B).
By using a quantitative immunoblotting technique on protein extracts of human macrovascular and microvascular endothelial cells, we have analyzed the self-reactive repertoires of IgG from 20 patients with limited cutaneous SSc, 40 patients with diffuse SSc and 60 age- and sex-matched healthy controls. Serum IgG from 15/20 patients with limited cutaneous SSc and anti-centromere antibodies bound to at least one of the two 75- and 85-kDa protein bands in the different endothelial cell extracts, whereas IgG from healthy controls or patients with diffuse SSc did not. N-terminal sequencing of the 75- and 85-kDa bands identified CENP-B as the sole antigen in both bands. Moreover, IgG from all of the SSc patients who recognized the 75- and/or 85-kDa bands bound to a full-length recombinant CENP-B protein as assessed by ELISA, whereas IgG from other SSc patients did not. The main target of anti-endothelial cell antibodies in patients with limited cutaneous SSc is the nuclear and ubiquitous protein CENP-B.
Servettaz
Amélie
A
Université Paris--Descartes, faculté de Médecine, UPRES-EA 1833, Laboratoire d'Immunologie, Paris, France.
Tamby
Mathieu C
MC
Guilpain
Philippe
P
Reinbolt
Joseph
J
Garcia de la Penã-Lefebvre
Paloma
P
Allanore
Yannick
Y
Kahan
André
A
Meyer
Olivier
O
Guillevin
Loïc
L
Mouthon
Luc
L
D000918:Antibody Specificity; D000954:Antigens, Surface / Q000737:chemistry / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood / Q000737:chemistry / Q000378:metabolism*; D002478:Cells, Cultured; D051936:Centromere Protein B / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D042783:Endothelial Cells / Q000737:chemistry / Q000276:immunology*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000737:chemistry / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D045743:Scleroderma, Diffuse / Q000276:immunology*; D045745:Scleroderma, Limited / Q000276:immunology*
D000954:Antigens, Surface; D001323:Autoantibodies; C497926:CENPB protein, human; D051936:Centromere Protein B; D007074:Immunoglobulin G; D011994:Recombinant Proteins