Expression Patterns of Interferon Induced Genes in Newborns Exposed to Ro/SSA Autoantibodies in Utero

Gudny Ella Thorlacius¹, Malin Hedlund¹, Margarita Ivanchenko¹, Vijole Ottosson¹, Amina Ossoinak¹, Linda Lagnefeldt¹, Lars Rönnblom², Sven-Erik Sonesson³, Maija-Leena Eloranta⁴ and Marie Wahren-Herlenius¹, ¹Unit of Experimental Rheumatology, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden, Stockholm, Sweden, ²Department of Medical Sciences, Section of Rheumatology, Uppsala University, Uppsala, Sweden, Uppsala, Sweden, ³Pediatric Cardiology Unit, Department of Women´s and Children´s Health, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden, Stockholm, Sweden, ⁴Rheumatology and Science for Life Laboratory, Department of Medical Sciences, Uppsala University, Sweden, Uppsala, Sweden

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: autoantibodies, heart block, Interferons and systemic lupus erythematosus (SLE), Sjogren's syndrome

Session Information

Date: Tuesday, November 7, 2017

Title: Systemic Lupus Erythematosus – Human Etiology and Pathogenesis I

Session Type: ACR Concurrent Abstract Session

Session Time: 2:30PM-4:00PM

Background/Purpose: Women with Sjögren’s syndrome and autoantibodies against Ro/SSA are at risk for pregnancy complications, including neonatal lupus erythematosus (NLE) and a congenital heart block in the baby. Ro/SSA autoantibodies are also associated with expression of interferon (IFN) regulated genes. Treatment with hydroxychloroquine (HCQ), which alters type 1 IFN activity, is thought to reduce the risk of NLE. The pattern and magnitude of IFN expression and responses in Ro/SSA autoantibody exposed newborns has not been investigated.

Methods: Thirteen Ro/SSA autoantibody positive mothers either receiving no medication (Ro/SSA+) or treated with HCQ and/or azathioprine (Ro/SSA+T), and their newborn babies were included in the study, together with 8 healthy mother-baby pairs (HC). Blood was drawn from the mother and baby (cord) at birth, with immediate separation into plasma and PBMC. mRNA expression levels were measured using microarrays and used for calculating IFN scores. Cell surface expression of molecules was investigated by flow cytometry, and IFN-α in plasma and supernatants was analyzed by immunoassay. The ability of PBMCs from newborns to produce IFN-α in response to autoantibody exposure was tested by stimulation with 10% plasma in cell culture for 24h.

Results: As expected, mRNA expression patterns in cells of SSA+ mothers showed enrichment of type I IFN pathways compared to HC mothers, and mothers from the Ro/SSA+ group had a higher IFN score and higher levels of IFN-α than HC mothers. Notably, also in newborns of Ro/SSA+ mothers, there was an enrichment of type I IFN pathways and high IFN score compared to newborns of HC mothers, and maternal and baby IFN scores had a significant, positive correlation (Pearson r=0.8128, p<0.0001). However, babies in the Ro/SSA+T group, whose mothers received immunomodulatory treatment, had an IFN score with values comparable to HC babies, while the maternal Ro/SSA+T IFN scores did not differ from those of non-treated mothers. Activation of CD14+ monocytes, in the form of increased MHC class II surface expression was observed in the Ro/SSA+ exposed newborns. PBMCs from both HC and Ro/SSA+ newborns cultured with Ro/SSA+ plasma produced IFN-α.

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 was partly reversed by maternal treatment with HCQ or other immunomodulatory drugs. PBMCs from babies are capable of producing IFN-α after exposure to Ro/SSA+ plasma. There is a measurable activation of the type I IFN system in Ro/SSA autoantibody exposed fetuses which may contribute to the risk of NLE.

Disclosure: G. E. Thorlacius, None; M. Hedlund, None; M. Ivanchenko, None; V. Ottosson, None; A. Ossoinak, None; L. Lagnefeldt, None; L. Rönnblom, None; S. E. Sonesson, None; M. L. Eloranta, None; M. Wahren-Herlenius, None.

To cite this abstract in AMA style:

Thorlacius GE, Hedlund M, Ivanchenko M, Ottosson V, Ossoinak A, Lagnefeldt L, Rönnblom L, Sonesson SE, Eloranta ML, Wahren-Herlenius M. Expression Patterns of Interferon Induced Genes in Newborns Exposed to Ro/SSA Autoantibodies in Utero [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/expression-patterns-of-interferon-induced-genes-in-newborns-exposed-to-rossa-autoantibodies-in-utero/. Accessed .

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