Molecular recognition patterns of anti-topoisomerase I-antibodies in patients with systemic sclerosis before and after autologous stem cell transplantation

TY - JOUR

T1 - Molecular recognition patterns of anti-topoisomerase I-antibodies in patients with systemic sclerosis before and after autologous stem cell transplantation

AU - Glaeser, L

AU - Henes, J

AU - Kötter, I

AU - Vogel, W

AU - Kanz, L

AU - Klein, R

PY - 2018/2

Y1 - 2018/2

N2 - 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.

AB - 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.

UR - http://europepmc.org/abstract/med/29465357

M3 - SCORING: Journal article

C2 - 29465357

VL - 36

SP - 28

EP - 35

JO - CLIN EXP RHEUMATOL

JF - CLIN EXP RHEUMATOL

SN - 0392-856X

IS - 113(4)

ER -