The following is a summary of “Functional autoantibodies in systemic sclerosis: influence of autologous stem cell transplantation and correlation with clinical outcome,” published in the June 2023 issue of Rheumatology by Bankamp, et al.

For a study, researchers sought to assess the impact of autologous stem cell transplantation (aSCT) on functional antibodies (abs) targeting the angiotensin II type-1 receptor (AT₁R) and topoisomerase-I (topo-I) in patients with systemic sclerosis (SSc) and to analyze their prognostic significance.

A total of 43 SSc patients who underwent aSCT were included in the analysis. Among them, 31 patients achieved a favorable outcome after aSCT (group 1), while 12 patients showed no response or experienced a relapse (group 2). Serum samples from the patients were collected before and after aSCT (median follow-up of 28 months, range 4-217 months) and tested for anti-AT1R and anti-topo-I antibodies using ELISA and a luminometric assay (LA) that utilized AT₁R-expressing Huh7 cells to measure inhibitory or stimulatory anti-AT₁R antibodies. The capacity of anti-topo-I antibodies to inhibit enzyme function was also assessed.

Prior to aSCT, 70% of the SSc patients had anti-topo-I antibodies, and 51% had anti-AT₁R antibodies based on ELISA. Anti-topo-I antibodies were found to inhibit topo-I enzyme function consistently. In the LA, 40% of patients had stimulatory anti-AT₁R antibodies, while 12% had inhibitory anti-AT₁R antibodies. After aSCT, there was a significant decrease in the reactivity of both anti-topo-I and anti-AT₁R antibodies as measured by ELISA. Before aSCT, patients in group 2 had significantly higher anti-topo-I reactivity levels than those in group 1 (P < 0.001). In contrast, there was no difference in anti-AT₁R antibody levels between the two groups based on ELISA. Stimulatory anti-AT₁R antibodies detected by LA were exclusively found in patients in group 1.

ASCT did not influence the reactivity of functionally active anti-AT₁R antibodies, whereas anti-topo-I antibodies decreased after aSCT. The consistent inhibition of topo-I enzyme function by anti-topo-I antibodies supports the notion of a pathogenic role for the topo-I antigen/antibody system in SSc. Higher levels of anti-topo-I reactivity before aSCT were associated with an unfavorable prognosis, while the presence of stimulatory anti-AT₁R antibodies was linked to a favorable outcome after aSCT.

Source: academic.oup.com/rheumatology/article-abstract/62/6/2168/6759365?redirectedFrom=fulltext