Objectives Autoimmune congenital heart block (CHB) is associated with placental transcytosis of maternal autoantibodies directed against Ro/SS-A and La/SS-B. However, only about 2% of children born to mothers with the respective antibodies are affected, indicating that further risk factors exist, which are not yet fully understood. In this study, we investigated whether a maternal type I interferon (IFN) signature represents a risk factor for the development of CHB.
Methods Blood samples, clinical data and serological parameters from 9 women with CHB pregnancies, 14 pregnant women with antibodies against Ro/SS-A but without a CHB complication and another 30 healthy pregnant women as controls were studied. SIGLEC1 expression was measured by flow cytometry and was correlated to plasma IFN-α levels measured by ELISA, and IFN-γ-induced protein 10 (IP-10) levels measured by Bio-Plex technique.
Results Mothers of affected children had a significantly higher expression of SIGLEC1 (p=0.0034) and IFN-α (p=0.014), but not of IP-10 (p=0.14, all MWU) compared to mothers of unaffected children. SIGLEC1 and IFN-α expression were reduced by hydroxychloroquine and oral glucocorticoids.
Conclusions High expression of SIGLEC1 in pregnant women with autoantibodies against Ro/SS-A indicates an enhanced risk for CHB development, and these women may benefit especially from IFN-α directed therapy, for example with hydroxychloroquine.
- congenital heart block
- neonatal lupus syndrome
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Contributors ARL, FS, KR, TR and TD: conception, design, analysis and interpretation of data.
ARL: drafting the article.
TD, TR and GRB: revising the manuscript critically for important intellectual content.
All authors read and approved the final manuscript.
Funding CRC initiative of the German Research Foundation (DFG) (SFB 650; TD and GRB). ARL receives a scholarship from the Leibniz Graduate School for Rheumatology (DRFZ).
Competing interests None declared.
Patient consent An own consent form approved by the ethics committee of the Charite Universitätsmedizin Berlin was used and signed by each study participant.
Ethics approval Ethics committee of the Charite Universitätsmedizin Berlin.
Provenance and peer review Not commissioned; externally peer reviewed.