The centromere kinesin-like protein, CENP-E. An autoantigen in systemic sclerosis.
OBJECTIVE
Autoantibodies directed against centromere proteins (CENPs) are a serologic feature in some patients with systemic sclerosis (SSc). Previous studies have focused on autoantibodies to CENPs A, B, and C. CENP-E is a recently described 312-kd protein that also localizes to the centromere. Therefore, we studied the presence of autoantibodies to recombinant CENP-E in patients with SSc.


METHODS
Sixty sera from patients with the SSc spectrum of diseases were screened for the presence of autoantibodies against CENP-E, by indirect immunofluorescence and immunoblotting using recombinant CENP-E protein. HLA class II alleles were determined by DNA oligotyping.


RESULTS
Among the SSc sera, 15 of 60 (25%) demonstrated antibody reactivity with recombinant CENP-E, and 14 of these 15 sera (93%) had antibodies directed against another CENP. Anti-CENP-E was seen in 13 of 30 sera with anti-CENP (43%). All patients with anti-CENP-E had a limited form of SSc, known as the CREST variant (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasias). When patients with anti-CENPs A, B, or C were compared with patients with anti-CENP-E, no unique clinical features in the anti-CENP-E positive group were identified. Ninety-three percent of the patients with anti-CENP-E had HLA-DQB1 alleles that had polar amino acids at position 26 (primarily DQB1*05), similar to patients with other CENP autoantibodies.


CONCLUSIONS
Antibodies to CENP-E are common in patients with SSc, and are seen in higher frequency in sera from patients with a limited form, or CREST variant, of the disease.
Rattner
J B
JB
Department of Anatomy, University of Calgary, Alberta, Canada.
Rees
J
J
Arnett
F C
FC
Reveille
J D
JD
Goldstein
R
R
Fritzler
M J
MJ
D001323:Autoantibodies / Q000097:blood; D015153:Blotting, Western; D002503:Centromere / Q000737:chemistry*; D002868:Chromosomal Proteins, Non-Histone / Q000032:analysis / Q000276:immunology*; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D005802:Genes, MHC Class II / Q000235:genetics / Q000276:immunology; D006801:Humans; D016547:Kinesins / Q000032:analysis / Q000276:immunology; D008875:Middle Aged; D009841:Oligonucleotides / Q000032:analysis; D011994:Recombinant Proteins / Q000276:immunology; D012595:Scleroderma, Systemic / Q000276:immunology
D001323:Autoantibodies; D002868:Chromosomal Proteins, Non-Histone; D018076:DNA, Complementary; D009841:Oligonucleotides; D011994:Recombinant Proteins; C068688:centromere protein E; D016547:Kinesins