Pos1431 immune cells and their effector functions in neonates born to anti-ro/la positive women

Background Neonatal lupus, including autoimmune congenital heart block, is a passively acquired autoimmune condition dependent on placental transfer of maternal Ro/La autoantibodies to the fetus. The mothers are commonly diagnosed with Sjögren’s syndrome or systemic lupus erythematosus, and present with elevated plasma interferon (IFN) levels and signs of immune activation. Recent studies demonstrate both a correlation between the maternal and neonatal IFN-scores, as well as elevated plasma IFNα levels in the neonates. Whether IFNα can be produced by the fetus or whether it originates from the mother is not known. Objectives To characterize immune cells in Ro/La autoantibody-exposed neonates with regard to phenotypes, effector functions and cytokine production. Methods We used full spectrum multi-color flow cytometry staining for an array of cell phenotype, activation and proliferation markers combined with intracellular cytokine staining to cover the most important innate and adaptive immune cell populations in cord blood cells of anti-Ro/La-exposed (n=12) and non-exposed (n=6) newborns. Results We confirmed an increased surface expression of Sialic acid-binding Ig-like lectin-1 (Siglec-1) on CD14+ monocytes and further show increased Siglec-1 expression also on CD14-CD16+ non-classical monocytes and conventional dendritic cells in anti-Ro/La-exposed compared to healthy control neonates. We did not observe any major differences in general populations such as CD4+, CD8+ or gamma delta T cells. However, we found a decreased frequency of regulatory CD4+ FoxP3+ T cells in the autoantibody-exposed newborns. In line with this, we observed an increase in conventional CD4+ FoxP3- T cells and that these cells have less of a naïve phenotype with significantly lower frequency of CD62L+ and more CD69-expressing cells in the CD4+ FoxP3- population. Interestingly, Ro/La-exposed newborns also had less CD5-expressing CD19+ B cells compared to healthy newborns, while the frequency of CD19+ CD5- B cells was not affected. Further, we noted a decreased surface expression of CD19 and CD11b on both these CD19+ subpopulations. Interestingly, for neonates born to mothers with high levels of all three of Ro52, Ro60 and La autoantibodies, we also found intracellular cytokine IFNα and TNFα production in B cell, dendritic cell, and monocyte populations. Conclusion Together, our data provide valuable insight into the effects of Ro/La autoantibody exposure in utero on immune activation of both innate and adaptive immune cell populations in exposed fetuses, enhancing our understanding of the immunological basis of neonatal lupus. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests None Declared.