1. Functional autoantibodies in systemic sclerosis: influence of autologous stem cell transplantation and correlation with clinical outcome.
- Author
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Bankamp, Lukas, Preuß, Beate, Pecher, Ann-Christin, Vogel, Wichard, Henes, Jörg, and Klein, Reinhild
- Subjects
AUTOANTIBODIES ,SYSTEMIC scleroderma ,AUTOGRAFTS ,TREATMENT effectiveness ,DISEASE relapse ,ENZYMES ,ENZYME-linked immunosorbent assay ,DESCRIPTIVE statistics ,ANGIOTENSIN receptors ,HEMATOPOIETIC stem cell transplantation ,DISEASE complications - Abstract
Objectives To evaluate the effect of autologous stem cell transplantation (aSCT) on functional antibodies (abs) to the angiotensin II type-1-receptor (AT
1 R) and topoisomerase-I (topo-I) in SSc-patients and to analyse their prognostic relevance. Material and methods Forty-three SSc-patients in whom aSCT was performed were analysed. Thirty-one patients had a favourable outcome after aSCT (group 1), 12 patients showed no response or relapse (group 2). Patients' sera were tested for anti-AT1 R and anti-topo-I antibodies by ELISA and in a luminometric assay (LA) using AT1 R-expressing Huh7-cells for inhibitory or stimulatory anti-AT1 R antibodies before and after aSCT (4–217 months, median 28 months). Anti-topo-I antibodies were also analysed for their capacity to inhibit enzyme function. Results A total of 70% of the SSc patients had anti-topo-I- and 51% anti-AT1 R antibodies in the ELISA before aSCT. In all instances, anti-topo-I antibodies inhibited topo-I-enzyme function. In the LA, 40% had stimulatory and 12% inhibitory anti-AT1 R antibodies. Anti-topo-I- and anti-AT1 R-reactivity (ELISA) significantly decreased after aSCT. Before aSCT, anti-topo-I-reactivity was significantly higher in group 2 patients than in group 1 patients (P < 0.001), while there was no difference between both groups for anti-AT1 R antibodies detected by ELISA. Stimulatory anti-AT1 R antibodies detected by LA were confined to group 1-patients. Conclusions Reactivity of functionally active anti-AT1 R antibodies was not influenced by aSCT, while anti-topo-I antibodies decreased after aSCT. The fact that anti-topo-I antibodies inhibited enzyme function in all instances supports the hypothesis of a pathogenetic role of the topo-I antigen/antibody-system in SSc. High anti-topo-I reactivity before aSCT was associated with an unfavourable, presence of stimulatory anti-AT1R antibodies with a favourable course after aSCT. [ABSTRACT FROM AUTHOR]- Published
- 2023
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