Type I IFN system activation in newborns exposed to Ro/SSA and La/SSB autoantibodies in utero
Identifieur interne : 000797 ( Pmc/Curation ); précédent : 000796; suivant : 000798Type I IFN system activation in newborns exposed to Ro/SSA and La/SSB autoantibodies in utero
Auteurs : Malin Hedlund [Suède] ; Gudny Ella Thorlacius [Suède] ; Margarita Ivanchenko [Suède] ; Vijole Ottosson [Suède] ; Nikolaos Kyriakidis [Suède, Équateur] ; Linda Lagnefeldt [Suède] ; Joanna Tingström [Suède] ; Allan Sirsjö [Suède] ; Anders A. Bengtsson [Suède] ; Emma Aronsson [Suède] ; Kristina Gemzell-Danielsson [Suède] ; Lars Ronnblom [Suède] ; Gunnar Bergman [Suède] ; Alexander Espinosa [Suède] ; Sven-Erik Sonesson [Suède] ; Maija-Leena Eloranta [Suède] ; Marie Wahren-Herlenius [Suède]Source :
- RMD Open [ 2056-5933 ] ; 2020.
Abstract
In utero exposure of the fetus to Ro/La autoantibodies may lead to congenital heart block (CHB). In the mother, these autoantibodies are associated with activation of the type I interferon (IFN)-system. As maternal autoantibodies are transferred to the fetus during pregnancy, we investigated whether the type I IFN-system is activated also in newborns of anti-Ro/La positive mothers, and whether fetal IFN activation is affected by maternal immunomodulatory treatment.
Blood drawn at birth from anti-Ro/La positive mothers, their newborns and healthy control pairs was separated into plasma and peripheral blood mononuclear cells (PBMC). PBMC were analysed directly or cultured. mRNA expression was analysed by microarrays, cell surface markers by flow cytometry, and IFNα levels by immunoassays.
We observed increased expression of IFN-regulated genes and elevated plasma IFNα levels not only in anti-Ro/La positive women, but also in their newborns. CD14+ monocytes of both anti-Ro/La positive mothers and their neonates showed increased expression of Sialic acid-binding Ig-like lectin-1, indicating cellular activation. Notably, the IFN score of neonates born to mothers receiving immunomodulatory treatment was similar to that of controls, despite persistent IFN activation in the mothers. In both maternal and neonatal PBMC, IFNα production was induced when cells were cultured with anti-Ro/La positive plasma.
Ro/La autoantibody-exposed neonates at risk of CHB have signs of an activated immune system with an IFN signature. This study further demonstrates that neonatal cells can produce IFNα when exposed to autoantibody-containing plasma, and that maternal immunomodulatory treatment may diminish the expression of IFN-regulated genes in the fetus.
Url:
DOI: 10.1136/rmdopen-2019-000989
PubMed: 31958275
PubMed Central: 7046945
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<country xml:lang="fr">Suède</country>
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<author><name sortKey="Thorlacius, Gudny Ella" sort="Thorlacius, Gudny Ella" uniqKey="Thorlacius G" first="Gudny Ella" last="Thorlacius">Gudny Ella Thorlacius</name>
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<author><name sortKey="Ottosson, Vijole" sort="Ottosson, Vijole" uniqKey="Ottosson V" first="Vijole" last="Ottosson">Vijole Ottosson</name>
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<author><name sortKey="Kyriakidis, Nikolaos" sort="Kyriakidis, Nikolaos" uniqKey="Kyriakidis N" first="Nikolaos" last="Kyriakidis">Nikolaos Kyriakidis</name>
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<author><name sortKey="Tingstrom, Joanna" sort="Tingstrom, Joanna" uniqKey="Tingstrom J" first="Joanna" last="Tingström">Joanna Tingström</name>
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<author><name sortKey="Sirsjo, Allan" sort="Sirsjo, Allan" uniqKey="Sirsjo A" first="Allan" last="Sirsjö">Allan Sirsjö</name>
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,<addr-line content-type="city">Stockholm</addr-line>
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,<addr-line content-type="city">Stockholm</addr-line>
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<author><name sortKey="Ronnblom, Lars" sort="Ronnblom, Lars" uniqKey="Ronnblom L" first="Lars" last="Ronnblom">Lars Ronnblom</name>
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<author><name sortKey="Bergman, Gunnar" sort="Bergman, Gunnar" uniqKey="Bergman G" first="Gunnar" last="Bergman">Gunnar Bergman</name>
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<author><name sortKey="Espinosa, Alexander" sort="Espinosa, Alexander" uniqKey="Espinosa A" first="Alexander" last="Espinosa">Alexander Espinosa</name>
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<author><name sortKey="Sonesson, Sven Erik" sort="Sonesson, Sven Erik" uniqKey="Sonesson S" first="Sven-Erik" last="Sonesson">Sven-Erik Sonesson</name>
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,<country>Sweden</country>
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<author><name sortKey="Eloranta, Maija Leena" sort="Eloranta, Maija Leena" uniqKey="Eloranta M" first="Maija-Leena" last="Eloranta">Maija-Leena Eloranta</name>
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<author><name sortKey="Wahren Herlenius, Marie" sort="Wahren Herlenius, Marie" uniqKey="Wahren Herlenius M" first="Marie" last="Wahren-Herlenius">Marie Wahren-Herlenius</name>
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,<institution>Karolinska Institutet, Karolinska University Hospital</institution>
,<addr-line content-type="city">Stockholm</addr-line>
,<country>Sweden</country>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Type I IFN system activation in newborns exposed to Ro/SSA and La/SSB autoantibodies in utero</title>
<author><name sortKey="Hedlund, Malin" sort="Hedlund, Malin" uniqKey="Hedlund M" first="Malin" last="Hedlund">Malin Hedlund</name>
<affiliation wicri:level="1"><nlm:aff id="aff1"><institution content-type="department">Rheumatology Unit, Department of Medicine</institution>
,<institution>Karolinska Institutet, Karolinska University Hospital</institution>
,<addr-line content-type="city">Stockholm</addr-line>
,<country>Sweden</country>
</nlm:aff>
<country xml:lang="fr">Suède</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Thorlacius, Gudny Ella" sort="Thorlacius, Gudny Ella" uniqKey="Thorlacius G" first="Gudny Ella" last="Thorlacius">Gudny Ella Thorlacius</name>
<affiliation wicri:level="1"><nlm:aff id="aff1"><institution content-type="department">Rheumatology Unit, Department of Medicine</institution>
,<institution>Karolinska Institutet, Karolinska University Hospital</institution>
,<addr-line content-type="city">Stockholm</addr-line>
,<country>Sweden</country>
</nlm:aff>
<country xml:lang="fr">Suède</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Ivanchenko, Margarita" sort="Ivanchenko, Margarita" uniqKey="Ivanchenko M" first="Margarita" last="Ivanchenko">Margarita Ivanchenko</name>
<affiliation wicri:level="1"><nlm:aff id="aff1"><institution content-type="department">Rheumatology Unit, Department of Medicine</institution>
,<institution>Karolinska Institutet, Karolinska University Hospital</institution>
,<addr-line content-type="city">Stockholm</addr-line>
,<country>Sweden</country>
</nlm:aff>
<country xml:lang="fr">Suède</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Ottosson, Vijole" sort="Ottosson, Vijole" uniqKey="Ottosson V" first="Vijole" last="Ottosson">Vijole Ottosson</name>
<affiliation wicri:level="1"><nlm:aff id="aff1"><institution content-type="department">Rheumatology Unit, Department of Medicine</institution>
,<institution>Karolinska Institutet, Karolinska University Hospital</institution>
,<addr-line content-type="city">Stockholm</addr-line>
,<country>Sweden</country>
</nlm:aff>
<country xml:lang="fr">Suède</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Kyriakidis, Nikolaos" sort="Kyriakidis, Nikolaos" uniqKey="Kyriakidis N" first="Nikolaos" last="Kyriakidis">Nikolaos Kyriakidis</name>
<affiliation wicri:level="1"><nlm:aff id="aff1"><institution content-type="department">Rheumatology Unit, Department of Medicine</institution>
,<institution>Karolinska Institutet, Karolinska University Hospital</institution>
,<addr-line content-type="city">Stockholm</addr-line>
,<country>Sweden</country>
</nlm:aff>
<country xml:lang="fr">Suède</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff2"><institution content-type="department">Facultad de Ciencias de la Salud, Escuela de Medicina, Grupo de Investigación en Biotecnología Aplicada a Biomedicina (BIOMED)</institution>
,<institution>Universidad de Las Américas (UDLA)</institution>
,<addr-line content-type="city">Quito</addr-line>
,<country>Ecuador</country>
</nlm:aff>
<country xml:lang="fr">Équateur</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Lagnefeldt, Linda" sort="Lagnefeldt, Linda" uniqKey="Lagnefeldt L" first="Linda" last="Lagnefeldt">Linda Lagnefeldt</name>
<affiliation wicri:level="1"><nlm:aff id="aff3"><institution content-type="department">Pediatric Cardiology Unit, Department of Women's and Children's Health</institution>
,<institution>Karolinska Institutet, Karolinska University Hospital</institution>
,<addr-line content-type="city">Stockholm</addr-line>
,<country>Sweden</country>
</nlm:aff>
<country xml:lang="fr">Suède</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Tingstrom, Joanna" sort="Tingstrom, Joanna" uniqKey="Tingstrom J" first="Joanna" last="Tingström">Joanna Tingström</name>
<affiliation wicri:level="1"><nlm:aff id="aff1"><institution content-type="department">Rheumatology Unit, Department of Medicine</institution>
,<institution>Karolinska Institutet, Karolinska University Hospital</institution>
,<addr-line content-type="city">Stockholm</addr-line>
,<country>Sweden</country>
</nlm:aff>
<country xml:lang="fr">Suède</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Sirsjo, Allan" sort="Sirsjo, Allan" uniqKey="Sirsjo A" first="Allan" last="Sirsjö">Allan Sirsjö</name>
<affiliation wicri:level="1"><nlm:aff id="aff4"><institution content-type="department">Cardiovascular Research Centre, School of Health and Medical Sciences</institution>
,<institution>Örebro Univeristy</institution>
,<addr-line content-type="city">Örebro</addr-line>
,<country>Sweden</country>
</nlm:aff>
<country xml:lang="fr">Suède</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Bengtsson, Anders A" sort="Bengtsson, Anders A" uniqKey="Bengtsson A" first="Anders A" last="Bengtsson">Anders A. Bengtsson</name>
<affiliation wicri:level="1"><nlm:aff id="aff5"><institution content-type="department">Division of Rheumatology, Department of Clinical Sciences</institution>
,<institution>Lund University</institution>
,<addr-line content-type="city">Lund</addr-line>
,<country>Sweden</country>
</nlm:aff>
<country xml:lang="fr">Suède</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Aronsson, Emma" sort="Aronsson, Emma" uniqKey="Aronsson E" first="Emma" last="Aronsson">Emma Aronsson</name>
<affiliation wicri:level="1"><nlm:aff id="aff6"><institution content-type="department">Division of Obstetrics and Gynecology, Department of Women's and Children's Health</institution>
,<institution>Karolinska Institutet, Karolinska University Hospital</institution>
,<addr-line content-type="city">Stockholm</addr-line>
,<country>Sweden</country>
</nlm:aff>
<country xml:lang="fr">Suède</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Gemzell Danielsson, Kristina" sort="Gemzell Danielsson, Kristina" uniqKey="Gemzell Danielsson K" first="Kristina" last="Gemzell-Danielsson">Kristina Gemzell-Danielsson</name>
<affiliation wicri:level="1"><nlm:aff id="aff6"><institution content-type="department">Division of Obstetrics and Gynecology, Department of Women's and Children's Health</institution>
,<institution>Karolinska Institutet, Karolinska University Hospital</institution>
,<addr-line content-type="city">Stockholm</addr-line>
,<country>Sweden</country>
</nlm:aff>
<country xml:lang="fr">Suède</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Ronnblom, Lars" sort="Ronnblom, Lars" uniqKey="Ronnblom L" first="Lars" last="Ronnblom">Lars Ronnblom</name>
<affiliation wicri:level="1"><nlm:aff id="aff7"><institution content-type="department">Rheumatology, Department of Medical Sciences</institution>
,<institution>Science for Life Laboratory, Uppsala University</institution>
,<addr-line content-type="city">Uppsala</addr-line>
,<country>Sweden</country>
</nlm:aff>
<country xml:lang="fr">Suède</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Bergman, Gunnar" sort="Bergman, Gunnar" uniqKey="Bergman G" first="Gunnar" last="Bergman">Gunnar Bergman</name>
<affiliation wicri:level="1"><nlm:aff id="aff3"><institution content-type="department">Pediatric Cardiology Unit, Department of Women's and Children's Health</institution>
,<institution>Karolinska Institutet, Karolinska University Hospital</institution>
,<addr-line content-type="city">Stockholm</addr-line>
,<country>Sweden</country>
</nlm:aff>
<country xml:lang="fr">Suède</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Espinosa, Alexander" sort="Espinosa, Alexander" uniqKey="Espinosa A" first="Alexander" last="Espinosa">Alexander Espinosa</name>
<affiliation wicri:level="1"><nlm:aff id="aff1"><institution content-type="department">Rheumatology Unit, Department of Medicine</institution>
,<institution>Karolinska Institutet, Karolinska University Hospital</institution>
,<addr-line content-type="city">Stockholm</addr-line>
,<country>Sweden</country>
</nlm:aff>
<country xml:lang="fr">Suède</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Sonesson, Sven Erik" sort="Sonesson, Sven Erik" uniqKey="Sonesson S" first="Sven-Erik" last="Sonesson">Sven-Erik Sonesson</name>
<affiliation wicri:level="1"><nlm:aff id="aff3"><institution content-type="department">Pediatric Cardiology Unit, Department of Women's and Children's Health</institution>
,<institution>Karolinska Institutet, Karolinska University Hospital</institution>
,<addr-line content-type="city">Stockholm</addr-line>
,<country>Sweden</country>
</nlm:aff>
<country xml:lang="fr">Suède</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Eloranta, Maija Leena" sort="Eloranta, Maija Leena" uniqKey="Eloranta M" first="Maija-Leena" last="Eloranta">Maija-Leena Eloranta</name>
<affiliation wicri:level="1"><nlm:aff id="aff7"><institution content-type="department">Rheumatology, Department of Medical Sciences</institution>
,<institution>Science for Life Laboratory, Uppsala University</institution>
,<addr-line content-type="city">Uppsala</addr-line>
,<country>Sweden</country>
</nlm:aff>
<country xml:lang="fr">Suède</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Wahren Herlenius, Marie" sort="Wahren Herlenius, Marie" uniqKey="Wahren Herlenius M" first="Marie" last="Wahren-Herlenius">Marie Wahren-Herlenius</name>
<affiliation wicri:level="1"><nlm:aff id="aff1"><institution content-type="department">Rheumatology Unit, Department of Medicine</institution>
,<institution>Karolinska Institutet, Karolinska University Hospital</institution>
,<addr-line content-type="city">Stockholm</addr-line>
,<country>Sweden</country>
</nlm:aff>
<country xml:lang="fr">Suède</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
</analytic>
<series><title level="j">RMD Open</title>
<idno type="eISSN">2056-5933</idno>
<imprint><date when="2020">2020</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><sec><title>Objective</title>
<p>In utero exposure of the fetus to Ro/La autoantibodies may lead to congenital heart block (CHB). In the mother, these autoantibodies are associated with activation of the type I interferon (IFN)-system. As maternal autoantibodies are transferred to the fetus during pregnancy, we investigated whether the type I IFN-system is activated also in newborns of anti-Ro/La positive mothers, and whether fetal IFN activation is affected by maternal immunomodulatory treatment.</p>
</sec>
<sec><title>Methods</title>
<p>Blood drawn at birth from anti-Ro/La positive mothers, their newborns and healthy control pairs was separated into plasma and peripheral blood mononuclear cells (PBMC). PBMC were analysed directly or cultured. mRNA expression was analysed by microarrays, cell surface markers by flow cytometry, and IFNα levels by immunoassays.</p>
</sec>
<sec><title>Results</title>
<p>We observed increased expression of IFN-regulated genes and elevated plasma IFNα levels not only in anti-Ro/La positive women, but also in their newborns. CD14<sup>+</sup>
monocytes of both anti-Ro/La positive mothers and their neonates showed increased expression of Sialic acid-binding Ig-like lectin-1, indicating cellular activation. Notably, the IFN score of neonates born to mothers receiving immunomodulatory treatment was similar to that of controls, despite persistent IFN activation in the mothers. In both maternal and neonatal PBMC, IFNα production was induced when cells were cultured with anti-Ro/La positive plasma.</p>
</sec>
<sec><title>Conclusions</title>
<p>Ro/La autoantibody-exposed neonates at risk of CHB have signs of an activated immune system with an IFN signature. This study further demonstrates that neonatal cells can produce IFNα when exposed to autoantibody-containing plasma, and that maternal immunomodulatory treatment may diminish the expression of IFN-regulated genes in the fetus.</p>
</sec>
</div>
</front>
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</div1>
</back>
</TEI>
<pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">RMD Open</journal-id>
<journal-id journal-id-type="iso-abbrev">RMD Open</journal-id>
<journal-id journal-id-type="hwp">rmdopen</journal-id>
<journal-id journal-id-type="publisher-id">rmdopen</journal-id>
<journal-title-group><journal-title>RMD Open</journal-title>
</journal-title-group>
<issn pub-type="epub">2056-5933</issn>
<publisher><publisher-name>BMJ Publishing Group</publisher-name>
<publisher-loc>BMA House, Tavistock Square, London, WC1H 9JR</publisher-loc>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">31958275</article-id>
<article-id pub-id-type="pmc">7046945</article-id>
<article-id pub-id-type="publisher-id">rmdopen-2019-000989</article-id>
<article-id pub-id-type="doi">10.1136/rmdopen-2019-000989</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Sjögren Syndrome</subject>
</subj-group>
<subj-group subj-group-type="hwp-journal-coll"><subject>1506</subject>
</subj-group>
<series-title>Original article</series-title>
</article-categories>
<title-group><article-title>Type I IFN system activation in newborns exposed to Ro/SSA and La/SSB autoantibodies in utero</article-title>
</title-group>
<contrib-group><contrib id="author-46311430" contrib-type="author"><name><surname>Hedlund</surname>
<given-names>Malin</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
</contrib>
<contrib id="author-51216313" contrib-type="author"><name><surname>Thorlacius</surname>
<given-names>Gudny Ella</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
</contrib>
<contrib id="author-52439470" contrib-type="author"><name><surname>Ivanchenko</surname>
<given-names>Margarita</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
</contrib>
<contrib id="author-46311424" contrib-type="author"><name><surname>Ottosson</surname>
<given-names>Vijole</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
</contrib>
<contrib id="author-52439484" contrib-type="author"><name><surname>Kyriakidis</surname>
<given-names>Nikolaos</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
<xref ref-type="aff" rid="aff2">2</xref>
</contrib>
<contrib id="author-69138714" contrib-type="author"><name><surname>Lagnefeldt</surname>
<given-names>Linda</given-names>
</name>
<xref ref-type="aff" rid="aff3">3</xref>
</contrib>
<contrib id="author-24286030" contrib-type="author"><name><surname>Tingström</surname>
<given-names>Joanna</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
</contrib>
<contrib id="author-52439519" contrib-type="author"><name><surname>Sirsjö</surname>
<given-names>Allan</given-names>
</name>
<xref ref-type="aff" rid="aff4">4</xref>
</contrib>
<contrib id="author-51522776" contrib-type="author"><name><surname>Bengtsson</surname>
<given-names>Anders A</given-names>
</name>
<xref ref-type="aff" rid="aff5">5</xref>
</contrib>
<contrib id="author-52439531" contrib-type="author"><name><surname>Aronsson</surname>
<given-names>Emma</given-names>
</name>
<xref ref-type="aff" rid="aff6">6</xref>
</contrib>
<contrib id="author-52439537" contrib-type="author"><name><surname>Gemzell-Danielsson</surname>
<given-names>Kristina</given-names>
</name>
<xref ref-type="aff" rid="aff6">6</xref>
</contrib>
<contrib id="author-45756542" contrib-type="author"><name><surname>Ronnblom</surname>
<given-names>Lars</given-names>
</name>
<xref ref-type="aff" rid="aff7">7</xref>
</contrib>
<contrib id="author-64893247" contrib-type="author"><name><surname>Bergman</surname>
<given-names>Gunnar</given-names>
</name>
<xref ref-type="aff" rid="aff3">3</xref>
</contrib>
<contrib id="author-52054006" contrib-type="author"><name><surname>Espinosa</surname>
<given-names>Alexander</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
</contrib>
<contrib id="author-64893228" contrib-type="author"><name><surname>Sonesson</surname>
<given-names>Sven-Erik</given-names>
</name>
<xref ref-type="aff" rid="aff3">3</xref>
</contrib>
<contrib id="author-22409140" contrib-type="author"><name><surname>Eloranta</surname>
<given-names>Maija-Leena</given-names>
</name>
<xref ref-type="aff" rid="aff7">7</xref>
</contrib>
<contrib id="author-56055848" contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid" authenticated="false">http://orcid.org/0000-0002-0915-7245</contrib-id>
<name><surname>Wahren-Herlenius</surname>
<given-names>Marie</given-names>
</name>
<xref ref-type="aff" rid="aff1">1</xref>
</contrib>
</contrib-group>
<aff id="aff1"><label>1</label>
<institution content-type="department">Rheumatology Unit, Department of Medicine</institution>
,<institution>Karolinska Institutet, Karolinska University Hospital</institution>
,<addr-line content-type="city">Stockholm</addr-line>
,<country>Sweden</country>
</aff>
<aff id="aff2"><label>2</label>
<institution content-type="department">Facultad de Ciencias de la Salud, Escuela de Medicina, Grupo de Investigación en Biotecnología Aplicada a Biomedicina (BIOMED)</institution>
,<institution>Universidad de Las Américas (UDLA)</institution>
,<addr-line content-type="city">Quito</addr-line>
,<country>Ecuador</country>
</aff>
<aff id="aff3"><label>3</label>
<institution content-type="department">Pediatric Cardiology Unit, Department of Women's and Children's Health</institution>
,<institution>Karolinska Institutet, Karolinska University Hospital</institution>
,<addr-line content-type="city">Stockholm</addr-line>
,<country>Sweden</country>
</aff>
<aff id="aff4"><label>4</label>
<institution content-type="department">Cardiovascular Research Centre, School of Health and Medical Sciences</institution>
,<institution>Örebro Univeristy</institution>
,<addr-line content-type="city">Örebro</addr-line>
,<country>Sweden</country>
</aff>
<aff id="aff5"><label>5</label>
<institution content-type="department">Division of Rheumatology, Department of Clinical Sciences</institution>
,<institution>Lund University</institution>
,<addr-line content-type="city">Lund</addr-line>
,<country>Sweden</country>
</aff>
<aff id="aff6"><label>6</label>
<institution content-type="department">Division of Obstetrics and Gynecology, Department of Women's and Children's Health</institution>
,<institution>Karolinska Institutet, Karolinska University Hospital</institution>
,<addr-line content-type="city">Stockholm</addr-line>
,<country>Sweden</country>
</aff>
<aff id="aff7"><label>7</label>
<institution content-type="department">Rheumatology, Department of Medical Sciences</institution>
,<institution>Science for Life Laboratory, Uppsala University</institution>
,<addr-line content-type="city">Uppsala</addr-line>
,<country>Sweden</country>
</aff>
<author-notes><corresp><label>Correspondence to</label>
Professor Marie Wahren-Herlenius; <email>marie.wahren@ki.se</email>
</corresp>
<fn fn-type="other"><p>MH and GET are joint first authors.</p>
</fn>
</author-notes>
<pub-date pub-type="collection"><year>2020</year>
</pub-date>
<pub-date pub-type="epub"><day>7</day>
<month>1</month>
<year>2020</year>
</pub-date>
<volume>6</volume>
<issue>1</issue>
<elocation-id>e000989</elocation-id>
<history><date date-type="received"><day>25</day>
<month>4</month>
<year>2019</year>
</date>
<date date-type="rev-recd"><day>08</day>
<month>11</month>
<year>2019</year>
</date>
<date date-type="accepted"><day>17</day>
<month>11</month>
<year>2019</year>
</date>
</history>
<permissions><copyright-statement>© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.</copyright-statement>
<copyright-year>2020</copyright-year>
<license license-type="open-access"><ali:license_ref start_date="2020-03-01">http://creativecommons.org/licenses/by-nc/4.0/</ali:license_ref>
<license-p>This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by-nc/4.0/">http://creativecommons.org/licenses/by-nc/4.0/</ext-link>
.</license-p>
</license>
</permissions>
<self-uri xlink:title="pdf" xlink:href="rmdopen-2019-000989.pdf"></self-uri>
<abstract><sec><title>Objective</title>
<p>In utero exposure of the fetus to Ro/La autoantibodies may lead to congenital heart block (CHB). In the mother, these autoantibodies are associated with activation of the type I interferon (IFN)-system. As maternal autoantibodies are transferred to the fetus during pregnancy, we investigated whether the type I IFN-system is activated also in newborns of anti-Ro/La positive mothers, and whether fetal IFN activation is affected by maternal immunomodulatory treatment.</p>
</sec>
<sec><title>Methods</title>
<p>Blood drawn at birth from anti-Ro/La positive mothers, their newborns and healthy control pairs was separated into plasma and peripheral blood mononuclear cells (PBMC). PBMC were analysed directly or cultured. mRNA expression was analysed by microarrays, cell surface markers by flow cytometry, and IFNα levels by immunoassays.</p>
</sec>
<sec><title>Results</title>
<p>We observed increased expression of IFN-regulated genes and elevated plasma IFNα levels not only in anti-Ro/La positive women, but also in their newborns. CD14<sup>+</sup>
monocytes of both anti-Ro/La positive mothers and their neonates showed increased expression of Sialic acid-binding Ig-like lectin-1, indicating cellular activation. Notably, the IFN score of neonates born to mothers receiving immunomodulatory treatment was similar to that of controls, despite persistent IFN activation in the mothers. In both maternal and neonatal PBMC, IFNα production was induced when cells were cultured with anti-Ro/La positive plasma.</p>
</sec>
<sec><title>Conclusions</title>
<p>Ro/La autoantibody-exposed neonates at risk of CHB have signs of an activated immune system with an IFN signature. This study further demonstrates that neonatal cells can produce IFNα when exposed to autoantibody-containing plasma, and that maternal immunomodulatory treatment may diminish the expression of IFN-regulated genes in the fetus.</p>
</sec>
</abstract>
<kwd-group><kwd>autoantibodies</kwd>
<kwd>autoimmune diseases</kwd>
<kwd>Sjøgren's syndrome</kwd>
</kwd-group>
<funding-group><award-group id="funding-1"><funding-source><institution-wrap><institution-id institution-id-type="FundRef">http://dx.doi.org/10.13039/501100008352</institution-id>
<institution>Stiftelsen Samariten</institution>
</institution-wrap>
</funding-source>
</award-group>
<award-group id="funding-2"><funding-source><institution-wrap><institution>Torsten och Ragnar Söderberg Foundation</institution>
</institution-wrap>
</funding-source>
</award-group>
<award-group id="funding-3"><funding-source><institution-wrap><institution-id institution-id-type="FundRef">http://dx.doi.org/10.13039/501100003793</institution-id>
<institution>Hjärt-Lungfonden</institution>
</institution-wrap>
</funding-source>
</award-group>
<award-group id="funding-4"><funding-source><institution-wrap><institution>The Ingegerd Johansson donation</institution>
</institution-wrap>
</funding-source>
</award-group>
<award-group id="funding-5"><funding-source><institution-wrap><institution-id institution-id-type="FundRef">http://dx.doi.org/10.13039/501100004359</institution-id>
<institution>Vetenskapsrådet</institution>
</institution-wrap>
</funding-source>
</award-group>
<award-group id="funding-6"><funding-source><institution-wrap><institution-id institution-id-type="FundRef">http://dx.doi.org/10.13039/501100007857</institution-id>
<institution>Stiftelsen Konung Gustaf V:s 80-årsfond</institution>
</institution-wrap>
</funding-source>
</award-group>
<award-group id="funding-7"><funding-source><institution-wrap><institution>The Swedish Society of Medicine</institution>
</institution-wrap>
</funding-source>
</award-group>
<award-group id="funding-8"><funding-source><institution-wrap><institution-id institution-id-type="FundRef">http://dx.doi.org/10.13039/501100004348</institution-id>
<institution>Stockholms Läns Landsting</institution>
</institution-wrap>
</funding-source>
</award-group>
<award-group id="funding-9"><funding-source><institution-wrap><institution>The Swedish Rheumatism Association</institution>
</institution-wrap>
</funding-source>
</award-group>
<award-group id="funding-10"><funding-source><institution-wrap><institution-id institution-id-type="FundRef">http://dx.doi.org/10.13039/501100004047</institution-id>
<institution>Karolinska Institutet</institution>
</institution-wrap>
</funding-source>
</award-group>
</funding-group>
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<meta-value>unlocked</meta-value>
</custom-meta>
</custom-meta-group>
</article-meta>
</front>
</pmc>
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