Background Autoimmune congenital heart block (CHB) is a severe manifestation of neonatal lupus syndrome that is associated with placental transcytosis of maternal autoantibodies directed against the ribonucleoproteins Ro/SS-A and, to a lesser extent, La/SS-B.(1) Around 2/3 of affected mothers are diagnosed with either systemic lupus erythematosus (SLE) or primary Sjögren's syndrome (pSS),(2) which are both pathogenically driven by an upregulation of type I interferons (IFN).(3)
Objectives Although the pleiotropic effects of type I IFN on the immune system are well documented, a potential role of type I IFN in the development of CHB has not yet been investigated. This study therefore aimed to compare maternal levels of type I IFN activation in affected and unaffected mothers, in order to provide first insights into a potential role of type I IFN in CHB development.
Methods Blood samples, clinical data and serological parameters from 9 women with CHB pregnancies, 15 pregnant women with antibodies against Ro/SS-A but without a CHB complication (“Disease Controls”, DC), and another 30 healthy pregnant women without the respective autoantibodies as controls were studied. Plasma levels of IFN-α (ELISA), interferon-gamma induced protein 10 (IP-10) (Bioplex®) and the expression of SIGLEC1 on CD14+ monocytes (flow cytometry) were analysed.
Results Pregnant females with a CHB complication 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 the DC group. Receiver operating curve (ROC) analysis between the CHB group and the DC group showed that a SIGLEC1 median fluorescence intensity (MFI) of >904 could distinguish between the groups with a sensitivity of 100% and a specificity of 64%, and a concentration of IFN-α >0.70 pg/ml with a sensitivity of 67% and a specificity of 86%. Healthy pregnant females without the respective autoantibodies had the lowest levels for all three parameters. In a cohort of 5 females, both the expression of SIGLEC1 and plasma levels of IFN-α were reduced by hydroxychloroquine and oral glucocorticoids.
Conclusions This is the first study to report increased type I IFN activation in pregnant females with a CHB complication. Also, we show here that IFN-α directed therapy, e.g. with hydroxychloroquine, may be especially beneficial in these females.
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Disclosure of Interest None declared