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OP0311 High maternal expression of siglec1 on cd14+ monocytes as a surrogate marker of a type i interferon signature is a risk factor for the development of autoimmune congenital heart block
  1. AR Lisney1,2,
  2. F Szelinski1,
  3. K Reiter1,
  4. G Burmester1,
  5. C Scholz3,
  6. T Rose1,2,
  7. T Dörner1,2
  1. 1Department of Rheumatology and Clinical Immunology, Charité, Universitätsmedizin Berlin
  2. 2German Rheumatism Research Center (DRFZ)
  3. 3Department of Obstetrics and Gynaecology, Charité, Universitätsmedizin Berlin, Berlin, Germany

Abstract

Background Autoimmune congenital heart block (CHB) is a severe manifestation of neonatal lupus syndrome that is associated with placental transcytosis of maternal autoantibodies directed against the ribonucleoproteins Ro/SS-A and, to a lesser extent, La/SS-B.(1) Around 2/3 of affected mothers are diagnosed with either systemic lupus erythematosus (SLE) or primary Sjögren's syndrome (pSS),(2) which are both pathogenically driven by an upregulation of type I interferons (IFN).(3)

Objectives Although the pleiotropic effects of type I IFN on the immune system are well documented, a potential role of type I IFN in the development of CHB has not yet been investigated. This study therefore aimed to compare maternal levels of type I IFN activation in affected and unaffected mothers, in order to provide first insights into a potential role of type I IFN in CHB development.

Methods Blood samples, clinical data and serological parameters from 9 women with CHB pregnancies, 15 pregnant women with antibodies against Ro/SS-A but without a CHB complication (“Disease Controls”, DC), and another 30 healthy pregnant women without the respective autoantibodies as controls were studied. Plasma levels of IFN-α (ELISA), interferon-gamma induced protein 10 (IP-10) (Bioplex®) and the expression of SIGLEC1 on CD14+ monocytes (flow cytometry) were analysed.

Results Pregnant females with a CHB complication 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 the DC group. Receiver operating curve (ROC) analysis between the CHB group and the DC group showed that a SIGLEC1 median fluorescence intensity (MFI) of >904 could distinguish between the groups with a sensitivity of 100% and a specificity of 64%, and a concentration of IFN-α >0.70 pg/ml with a sensitivity of 67% and a specificity of 86%. Healthy pregnant females without the respective autoantibodies had the lowest levels for all three parameters. In a cohort of 5 females, both the expression of SIGLEC1 and plasma levels of IFN-α were reduced by hydroxychloroquine and oral glucocorticoids.

Table 1.

Antibody profiles

Conclusions This is the first study to report increased type I IFN activation in pregnant females with a CHB complication. Also, we show here that IFN-α directed therapy, e.g. with hydroxychloroquine, may be especially beneficial in these females.

References

  1. Brito-Zeron P, Izmirly PM, Ramos-Casals M, Buyon JP, Khamashta MA. Autoimmune congenital heart block: complex and unusual situations. Lupus. 2016; 25(2):116–28.

  2. Brito-Zeron P, Izmirly PM, Ramos-Casals M, Buyon JP, Khamashta MA. The clinical spectrum of autoimmune congenital heart block. Nat Rev Rheumatol. 2015;11(5):301–12.

  3. Lopez de Padilla CM, Niewold TB. The type I interferons: Basic concepts and clinical relevance in immune-mediated inflammatory diseases. Gene. 2016;576(1 Pt 1):14–21.

References

Disclosure of Interest None declared

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