Aetiopathogenesis
Molecular recognition patterns of anti-topoisomerase I-antibodies in patients with systemic sclerosis before and after autologous stem cell transplantation
L. Glaeser1, J. Henes2, I. Kötter3, W. Vogel4, L. Kanz5, R. Klein6
- Department of Internal Medicine II, University of Tübingen, Germany.
- Department of Internal Medicine II, University of Tübingen, Germany.
- Department of Internal Medicine II, University of Tübingen, Germany.
- Department of Internal Medicine II, University of Tübingen, Germany.
- Department of Internal Medicine II, University of Tübingen, Germany.
- Department of Internal Medicine II, University of Tübingen, Germany. reinhild.klein@med.uni-tuebingen.de
CER10732
2018 Vol.36, N°4 ,Suppl.113
PI 0028, PF 0035
Aetiopathogenesis
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PMID: 29465357 [PubMed]
Received: 04/08/2017
Accepted : 05/12/2017
In Press: 13/02/2018
Published: 28/09/2018
Abstract
OBJECTIVES:
To evaluate the effect of autologous stem cell transplantation (aSCT) on antibody (ab) reactivity towards linear epitopes of topoisomerase-I (topo-I/Scl70) in patients with systemic sclerosis (SSc) and to correlate antibody reactivities with clinical outcome after aSCT.
METHODS:
Fourteen anti-topo-I/Scl70-positive SSc-patients were analysed before and after non-myeloablative aSCT. Five patients showed ongoing good response (group 1), 9 had primarily responded but later relapsed or did not respond (group 2). Patients’ sera were tested by ELISA against full length (fl) topo-I and 45 overlapping 25-mer peptides. Furthermore, for comparison sera from patients with anti-topo-I-negative SSc (n=12), other collagen disorders (n=6), and from 21 healthy controls (HC) were analysed.
RESULTS:
Anti-topo-I-positive SSc-sera showed significantly higher IgG-reactivity as compared to HC towards 34 of the 45 peptides. Especially peptide 39 (aa647-671) emerged as a immunodominant epitope being recognised predominantly by anti-topo-I-positive SSc-sera. Reactivity towards 17 of the 45 peptides decreased after aSCT in group 1- and 2-patients. Before aSCT, group 1-patients had lower antibody reactivity towards peptide 39 than group 2-patients. There was no change in peptide-specificity after aSCT.
CONCLUSIONS:
Reactivity towards topo-I-epitopes is heterogeneous in SSc, but peptide 39 (aa647-671) may be another immunodominant epitope besides the published epitope aa489-573. Antibody reactivity to this peptide 39 was higher in group 2- than in group 1-patients. Peptide recognition pattern did not change after aSCT.
