Background/Purpose: Ro/SSA autoantibodies and an IFN signature are commonly present in women with Sjögren’s syndrome and SLE. During pregnancy, the autoantibodies are transported across the placenta and are associated with a risk of neonatal lupus erythematosus (NLE) including a congenital heart block (CHB) in the baby. Hydroxychloroquine, which inhibits toll like receptor signaling and decreases activity in the type 1 IFN system has been suggested to decrease the risk of NLE. Whether activation of the interferon system occurs in the baby is however not known. In the present study we therefore investigated whether the type 1 IFN system is activated in Ro/SSA autoantibody exposed newborns.

Methods: Seven Ro/SSA autoantibody positive mothers receiving no medication and 3 mothers treated with hydroxychloroquine and/or azathioprine and their newborn babies were included in the study together with 8 healthy mother-baby pairs. Blood was drawn from the mother and cord at birth, with immediate separation into plasma and peripheral blood mononuclear cells (PBMCs). Autoantibodies were analyzed by ELISA and IFN-α by DELFIA. Cell surface expression of molecules was investigated by flow cytometry, and mRNA expression by microarrays. mRNA expression data was used for calculating an IFN score.

Results: Ro/SSA antibody positive women without treatment and their babies had higher levels of IFN-α than control mothers and control babies, respectively. Activation of the IFN system with increased expression of IFN-regulated genes was observed in both the Ro/SSA antibody positive women and their babies, with a significant correlation between maternal and fetal IFN-scores (R²=0.53, p=0.005). Further, increased expression of MHC class II was observed on CD14+ monocytes in the Ro/SSA antibody exposed babies, suggesting higher activation of these cells. In babies of mothers receiving immunomodulatory treatment, the IFN score was similar to that of healthy control babies.

Conclusion: Babies exposed to Ro/SSA autoantibodies in utero have circulating IFN-α, an IFN-signature in their PBMCs and increased MHC class II expression on the cell surface of monocytes, which is partly reversed by treatment with hydroxychloroquine or other immunomodulatory drugs. This study proposes that fetal activation of the type I IFN system may contribute to the risk of NLE.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/expression-of-ifn-regulated-genes-in-autoantibody-exposed-babies-in-utero/