Molecular recognition patterns of anti-topoisomerase I-antibodies in patients with systemic sclerosis before and after autologous stem cell transplantation
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Molecular recognition patterns of anti-topoisomerase I-antibodies in patients with systemic sclerosis before and after autologous stem cell transplantation. / Glaeser, L; Henes, J; Kötter, I; Vogel, W; Kanz, L; Klein, R.
In: CLIN EXP RHEUMATOL, Vol. 36, No. 113(4), 02.2018, p. 28-35.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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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 -