Association between interferon-I producing plasmacytoid dendritic cells and thrombotic antiphospholipid syndrome

Background: Thrombotic risk in antiphospholipid syndrome (APS) is conferred by the association of antiphospholipid (aPL) antibodies (first hit) with additional pro-coagulant stimulus (second hit), such as inflammation. Among inflammatory responses, the production of large amounts of interferon (IFN)...

Full description

Saved in:
Bibliographic Details
Published in:Lupus 2022-08, Vol.31 (9), p.1067-1077
Main Authors: Rosa dos Santos, Ana Paula, de Oliveira Vaz, Camila, Hounkpe, Bidossessi Wilfried, Jacintho, Bruna Cardoso, Oliveira, José Diogo, Tripiquia Vechiatto Mesquita, Gabriela Lisiane, Pereira dos Santos, Irene, Annichino-Bizzacchi, Joyce, Appenzeller, Simone, de Moraes Mazetto Fonseca, Bruna, Orsi, Fernanda Andrade
Format: Article
Language:English
Subjects:
Antiphospholipid antibodies
Antiphospholipid syndrome
Autoimmune diseases
Dendritic cells
Flow cytometry
Gene expression
Inflammation
Interferon
Intracellular
Leukocytes (mononuclear)
mRNA
Myxovirus resistance proteins
Oligonucleotides
Patients
Thrombosis
α-Interferon
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Background: Thrombotic risk in antiphospholipid syndrome (APS) is conferred by the association of antiphospholipid (aPL) antibodies (first hit) with additional pro-coagulant stimulus (second hit), such as inflammation. Among inflammatory responses, the production of large amounts of interferon (IFN)-I by plasmacytoid dendritic cells (pDCs) is at the basis of the pathophysiology of systemic autoimmune disorders, which raises the hypothesis that this mechanism could also be associated with vascular manifestations of APS. Purpose: Here, we determined the association of pDCs and IFN-I production with thrombotic APS. Research design: Patients with thrombotic primary (t-PAPS) and secondary APS (t-SAPS), asymptomatic aPL carriers and individuals without thrombosis (controls) were included. Data collection and analysis: Circulating pDCs and IFN-α intracellular expression (in the presence or not of oligodeoxynucleotides (CP) stimulus) were quantified by flow cytometry. The expression of five IFN-I inducing genes: ISG15, OASL, Ly6E, MX1, and OAS1 in mononuclear cells was determined by qPCR. Between-group differences were evaluated using chi-square or Kruskal–Wallis tests. Results: A total of 50 patients with t-PAPS, 50 patients with t-SAPS, 20 aPL carriers, and 50 individuals without thrombosis (controls) were included. Intracellular expression of IFN-α was increased after CPG stimulation in both t-SAPS (1.56%; IQR 1.07–2.02) and t-PAPS (0.96%; IQR 0.55–1.24), when compared to aPL carriers (0.71%; IQR 0.42–0.93) and controls (0.48%; IQR 0.24–0.78; p < .0001). ISG15, OASL, Ly6E, MX1, and OAS1 mRNA expressions were higher in t-SAPS (but not in t-PAPS) than in aPL carriers and controls. The expression of proteins and mRNA related to IFN-I response was similar between the triple aPL-positive profile and other aPL profiles. Conclusion: Our results indicate an association of IFN-I response and t-APS. Since IFN-I expression was not increased in aPL carriers or associated with a higher-risk aPL profile, this mechanism does not appear to be related to the presence of aPL alone. IFN-I response could possibly constitute a complementary mechanism for triggering clinical manifestations in APS.
ISSN:0961-2033
1477-0962
DOI:10.1177/09612033221101731