Background: High maternal anti-Ro52 and anti-Ro60 autoantibody titers are associated with risk of congenital heart block (CHB). Activation of the interferon (IFN) system, measured by an IFN score, may occur in individuals exposed to anti-Ro/La autoantibodies.

Objectives: In the present study, we investigated whether anti-Ro/La autoantibody titers correlate with IFN scores or the expression of individual genes in a genome-wide analysis using samples from autoantibody-exposed and non-exposed mothers and neonates at birth.

Methods: In all, 77 individuals were included in the study of which 45 were mothers sampled at delivery and 32 neonates, from which cord blood was obtained. Of the mothers, 26 were anti-Ro/La positive without a history of CHB, 12 had a history of CHB or carried a child with CHB and 7 were pregnant healthy controls without Ro/La antibodies. Of the 32 neonates, 27 had been exposed to anti-Ro/La in utero whereof 9 developed CHB and 18 did not, and 5 were born to mothers without Ro/La antibodies. RNA expression was analyzed by microarrays of PBMCs, and autoantibody titers for anti-Ro52, anti-Ro60 and anti-La were determined by ELISA. IFN scores were calculated from the microarray data using 13 interferon-induced genes, and the correlation of autoantibody levels with the interferon scores, or individual genes, was analyzed by Pearson correlation and linear regression.

Results: Maternal IFN scores correlated significantly with levels of anti-Ro52 (r=0.425 p=0.006), anti-Ro60 (r=0.359 p=0.021) and anti-La (r= 0.366 p=0.019). In neonates, both their anti-Ro52 (r=0.409 p=0.022) and anti-Ro60 (r=0.378 p=0.036) levels correlated significantly with the IFN score, while there was no significant correlation with anti-La levels. In analysis of individual genes, 1088 genes in the neonates were nominally significantly associated with anti-Ro52 levels, 929 with anti-Ro60 levels, and 215 with anti-La levels. The most significant association in the neonates was observed between anti-Ro60 levels and the expression of the genes VWF and PROCR with beta values of 0.667 (p=1.20e-06) and 1.039 (p=1.33e-06), respectively. Both genes are involved in blood coagulation. Neonatal anti-La levels associated with expression of genes NT5DC2 and CTSL with beta values 0.979 (p=6.93e-07) and 0.220 (p=1.41e-06). For maternal samples, no genes passed the Bonferroni corrected threshold for multiple testing when analyzing their association with anti-Ro/La levels. However, 702 genes were nominally significantly associated with anti-Ro52 levels, 562 with anti-Ro60 and 405 with anti-La levels.

Conclusion: This study demonstrates that levels of anti-Ro52 and anti-Ro60 autoantibodies positively associate with the IFN score in mothers as well as exposed neonates. Furthermore, expression of individual genes related to the coagulation system correlated with Ro60 antibody levels in the neonates, identifying a hitherto unexplored pathway with potential relevance for CHB.

REFERENCES: NIL.

Acknowledgements: NIL.

Disclosure of Interests: Lisa Rudolph: None declared, Malin Hedlund: None declared, Elina Richardsdotter Andersson: None declared, Vijole Ottosson: None declared, Joanna Tingström: None declared, Felicia Nordenstam: None declared, Gunnar Bergman: None declared, Sven-Erik Sonesson: None declared, Gudny Ella Thorlacius: None declared, Marie Wahren-Herlenius received an unrestricted grant from Jansen Pharmaceuticals.

© The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.