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High maternal expression of SIGLEC1 on monocytes as a surrogate marker of a type I interferon signature is a risk factor for the development of autoimmune congenital heart block.
Ann Rheum Dis. 2017 Aug; 76(8):1476-1480.AR

Abstract

OBJECTIVES

Autoimmune congenital heart block (CHB) is associated with placental transcytosis of maternal autoantibodies directed against Ro/SS-A and La/SS-B. However, only about 2% of children born to mothers with the respective antibodies are affected, indicating that further risk factors exist, which are not yet fully understood. In this study, we investigated whether a maternal type I interferon (IFN) signature represents a risk factor for the development of CHB.

METHODS

Blood samples, clinical data and serological parameters from 9 women with CHB pregnancies, 14 pregnant women with antibodies against Ro/SS-A but without a CHB complication and another 30 healthy pregnant women as controls were studied. SIGLEC1 expression was measured by flow cytometry and was correlated to plasma IFN-α levels measured by ELISA, and IFN-γ-induced protein 10 (IP-10) levels measured by Bio-Plex technique.

RESULTS

Mothers of affected children had a significantly higher expression of SIGLEC1 (p=0.0034) and IFN-α (p=0.014), but not of IP-10 (p=0.14, all MWU) compared to mothers of unaffected children. SIGLEC1 and IFN-α expression were reduced by hydroxychloroquine and oral glucocorticoids.

CONCLUSIONS

High expression of SIGLEC1 in pregnant women with autoantibodies against Ro/SS-A indicates an enhanced risk for CHB development, and these women may benefit especially from IFN-α directed therapy, for example with hydroxychloroquine.

Authors+Show Affiliations

Department of Rheumatology and Clinical Immunology, Charité Universitätsmedizin Berlin, Berlin, Germany. German Rheumatism Research Center Berlin (DRFZ), Berlin, Germany.Department of Rheumatology and Clinical Immunology, Charité Universitätsmedizin Berlin, Berlin, Germany.Department of Rheumatology and Clinical Immunology, Charité Universitätsmedizin Berlin, Berlin, Germany.Department of Rheumatology and Clinical Immunology, Charité Universitätsmedizin Berlin, Berlin, Germany.Department of Rheumatology and Clinical Immunology, Charité Universitätsmedizin Berlin, Berlin, Germany. German Rheumatism Research Center Berlin (DRFZ), Berlin, Germany.Department of Rheumatology and Clinical Immunology, Charité Universitätsmedizin Berlin, Berlin, Germany. German Rheumatism Research Center Berlin (DRFZ), Berlin, Germany.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28501799

Citation

Lisney, Anna R., et al. "High Maternal Expression of SIGLEC1 On Monocytes as a Surrogate Marker of a Type I Interferon Signature Is a Risk Factor for the Development of Autoimmune Congenital Heart Block." Annals of the Rheumatic Diseases, vol. 76, no. 8, 2017, pp. 1476-1480.
Lisney AR, Szelinski F, Reiter K, et al. High maternal expression of SIGLEC1 on monocytes as a surrogate marker of a type I interferon signature is a risk factor for the development of autoimmune congenital heart block. Ann Rheum Dis. 2017;76(8):1476-1480.
Lisney, A. R., Szelinski, F., Reiter, K., Burmester, G. R., Rose, T., & Dörner, T. (2017). High maternal expression of SIGLEC1 on monocytes as a surrogate marker of a type I interferon signature is a risk factor for the development of autoimmune congenital heart block. Annals of the Rheumatic Diseases, 76(8), 1476-1480. https://doi.org/10.1136/annrheumdis-2016-210927
Lisney AR, et al. High Maternal Expression of SIGLEC1 On Monocytes as a Surrogate Marker of a Type I Interferon Signature Is a Risk Factor for the Development of Autoimmune Congenital Heart Block. Ann Rheum Dis. 2017;76(8):1476-1480. PubMed PMID: 28501799.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - High maternal expression of SIGLEC1 on monocytes as a surrogate marker of a type I interferon signature is a risk factor for the development of autoimmune congenital heart block. AU - Lisney,Anna R, AU - Szelinski,Franziska, AU - Reiter,Karin, AU - Burmester,Gerd R, AU - Rose,Thomas, AU - Dörner,Thomas, Y1 - 2017/05/13/ PY - 2016/12/06/received PY - 2017/03/10/revised PY - 2017/04/09/accepted PY - 2017/5/16/pubmed PY - 2017/8/22/medline PY - 2017/5/15/entrez KW - SIGLEC1 KW - congenital heart block KW - interferon-α KW - neonatal lupus syndrome KW - sialoadhesin SP - 1476 EP - 1480 JF - Annals of the rheumatic diseases JO - Ann. Rheum. Dis. VL - 76 IS - 8 N2 - OBJECTIVES: Autoimmune congenital heart block (CHB) is associated with placental transcytosis of maternal autoantibodies directed against Ro/SS-A and La/SS-B. However, only about 2% of children born to mothers with the respective antibodies are affected, indicating that further risk factors exist, which are not yet fully understood. In this study, we investigated whether a maternal type I interferon (IFN) signature represents a risk factor for the development of CHB. METHODS: Blood samples, clinical data and serological parameters from 9 women with CHB pregnancies, 14 pregnant women with antibodies against Ro/SS-A but without a CHB complication and another 30 healthy pregnant women as controls were studied. SIGLEC1 expression was measured by flow cytometry and was correlated to plasma IFN-α levels measured by ELISA, and IFN-γ-induced protein 10 (IP-10) levels measured by Bio-Plex technique. RESULTS: Mothers of affected children had a significantly higher expression of SIGLEC1 (p=0.0034) and IFN-α (p=0.014), but not of IP-10 (p=0.14, all MWU) compared to mothers of unaffected children. SIGLEC1 and IFN-α expression were reduced by hydroxychloroquine and oral glucocorticoids. CONCLUSIONS: High expression of SIGLEC1 in pregnant women with autoantibodies against Ro/SS-A indicates an enhanced risk for CHB development, and these women may benefit especially from IFN-α directed therapy, for example with hydroxychloroquine. SN - 1468-2060 UR - https://www.unboundmedicine.com/medline/citation/28501799/High_maternal_expression_of_SIGLEC1_on_monocytes_as_a_surrogate_marker_of_a_type_I_interferon_signature_is_a_risk_factor_for_the_development_of_autoimmune_congenital_heart_block_ L2 - https://ard.bmj.com/cgi/pmidlookup?view=long&pmid=28501799 DB - PRIME DP - Unbound Medicine ER -