Associations between type I interferon and antiphospholipid antibody status differ between ancestral backgrounds

Taro Iwamoto, Jessica Dorschner, Meenakshi Jolly, Xiangyang Huang, Timothy B. Niewold

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Objective: The type I interferon pathway is activated in many patients with systemic lupus erythematosus (SLE), and anti-double-stranded DNA (dsDNA) and anti-RNA binding protein autoantibodies are correlated with high interferon-α (IFNα) activity. We studied whether antiphospholipid (APL) antibodies, which should not stimulate Toll-like receptors, are also associated with high levels of IFNα activity. Methods: Serum IFNα activity was measured in patients with SLE using the WISH cell bioassay. IgG APL, anti-RBP and anti-dsDNA antibodies were measured in the clinical laboratory, and standard clinical cut-offs were used to define the positive results. Results: High IFNα activity was associated with anti-RBP and anti-dsDNA antibodies in all three ancestral backgrounds. Strikingly, African-American subjects with a positive APL antibody test had higher IFNα activity than those without IgG APL antibodies. This was not shared with other ancestral backgrounds. This finding was independent of other autoantibody profiles, and clinical features did not differ between IgG APL antibody positive versus negative African-American patients. Conclusion: The difference in association between IFNα activity and IgG APL status between ancestral backgrounds supports differences in molecular pathogenesis. This may suggest B cell hyperactivity in the setting of type I IFN in African-Americans and could suggest ways to individualise therapy.

Original languageEnglish (US)
Article numbere000246
JournalLupus Science and Medicine
Volume5
Issue number1
DOIs
StatePublished - Jan 1 2018

Fingerprint

Interferon Type I
Antiphospholipid Antibodies
Interferons
African Americans
Immunoglobulin G
Systemic Lupus Erythematosus
Autoantibodies
RNA-Binding Proteins
Antibodies
Toll-Like Receptors
DNA
Biological Assay
B-Lymphocytes
Serum

Keywords

  • antiphospholipid antibodies
  • cytokines
  • systemic lupus erythematosus

ASJC Scopus subject areas

  • Immunology

Cite this

Associations between type I interferon and antiphospholipid antibody status differ between ancestral backgrounds. / Iwamoto, Taro; Dorschner, Jessica; Jolly, Meenakshi; Huang, Xiangyang; Niewold, Timothy B.

In: Lupus Science and Medicine, Vol. 5, No. 1, e000246, 01.01.2018.

Research output: Contribution to journalArticle

Iwamoto, Taro ; Dorschner, Jessica ; Jolly, Meenakshi ; Huang, Xiangyang ; Niewold, Timothy B. / Associations between type I interferon and antiphospholipid antibody status differ between ancestral backgrounds. In: Lupus Science and Medicine. 2018 ; Vol. 5, No. 1.
@article{1f6b1bda3e5e42a89bdfb46d9d64b3f4,
title = "Associations between type I interferon and antiphospholipid antibody status differ between ancestral backgrounds",
abstract = "Objective: The type I interferon pathway is activated in many patients with systemic lupus erythematosus (SLE), and anti-double-stranded DNA (dsDNA) and anti-RNA binding protein autoantibodies are correlated with high interferon-α (IFNα) activity. We studied whether antiphospholipid (APL) antibodies, which should not stimulate Toll-like receptors, are also associated with high levels of IFNα activity. Methods: Serum IFNα activity was measured in patients with SLE using the WISH cell bioassay. IgG APL, anti-RBP and anti-dsDNA antibodies were measured in the clinical laboratory, and standard clinical cut-offs were used to define the positive results. Results: High IFNα activity was associated with anti-RBP and anti-dsDNA antibodies in all three ancestral backgrounds. Strikingly, African-American subjects with a positive APL antibody test had higher IFNα activity than those without IgG APL antibodies. This was not shared with other ancestral backgrounds. This finding was independent of other autoantibody profiles, and clinical features did not differ between IgG APL antibody positive versus negative African-American patients. Conclusion: The difference in association between IFNα activity and IgG APL status between ancestral backgrounds supports differences in molecular pathogenesis. This may suggest B cell hyperactivity in the setting of type I IFN in African-Americans and could suggest ways to individualise therapy.",
keywords = "antiphospholipid antibodies, cytokines, systemic lupus erythematosus",
author = "Taro Iwamoto and Jessica Dorschner and Meenakshi Jolly and Xiangyang Huang and Niewold, {Timothy B.}",
year = "2018",
month = "1",
day = "1",
doi = "10.1136/lupus-2017-000246",
language = "English (US)",
volume = "5",
journal = "Lupus Science and Medicine",
issn = "2053-8790",
publisher = "BMJ Publishing Group",
number = "1",

}

TY - JOUR

T1 - Associations between type I interferon and antiphospholipid antibody status differ between ancestral backgrounds

AU - Iwamoto, Taro

AU - Dorschner, Jessica

AU - Jolly, Meenakshi

AU - Huang, Xiangyang

AU - Niewold, Timothy B.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Objective: The type I interferon pathway is activated in many patients with systemic lupus erythematosus (SLE), and anti-double-stranded DNA (dsDNA) and anti-RNA binding protein autoantibodies are correlated with high interferon-α (IFNα) activity. We studied whether antiphospholipid (APL) antibodies, which should not stimulate Toll-like receptors, are also associated with high levels of IFNα activity. Methods: Serum IFNα activity was measured in patients with SLE using the WISH cell bioassay. IgG APL, anti-RBP and anti-dsDNA antibodies were measured in the clinical laboratory, and standard clinical cut-offs were used to define the positive results. Results: High IFNα activity was associated with anti-RBP and anti-dsDNA antibodies in all three ancestral backgrounds. Strikingly, African-American subjects with a positive APL antibody test had higher IFNα activity than those without IgG APL antibodies. This was not shared with other ancestral backgrounds. This finding was independent of other autoantibody profiles, and clinical features did not differ between IgG APL antibody positive versus negative African-American patients. Conclusion: The difference in association between IFNα activity and IgG APL status between ancestral backgrounds supports differences in molecular pathogenesis. This may suggest B cell hyperactivity in the setting of type I IFN in African-Americans and could suggest ways to individualise therapy.

AB - Objective: The type I interferon pathway is activated in many patients with systemic lupus erythematosus (SLE), and anti-double-stranded DNA (dsDNA) and anti-RNA binding protein autoantibodies are correlated with high interferon-α (IFNα) activity. We studied whether antiphospholipid (APL) antibodies, which should not stimulate Toll-like receptors, are also associated with high levels of IFNα activity. Methods: Serum IFNα activity was measured in patients with SLE using the WISH cell bioassay. IgG APL, anti-RBP and anti-dsDNA antibodies were measured in the clinical laboratory, and standard clinical cut-offs were used to define the positive results. Results: High IFNα activity was associated with anti-RBP and anti-dsDNA antibodies in all three ancestral backgrounds. Strikingly, African-American subjects with a positive APL antibody test had higher IFNα activity than those without IgG APL antibodies. This was not shared with other ancestral backgrounds. This finding was independent of other autoantibody profiles, and clinical features did not differ between IgG APL antibody positive versus negative African-American patients. Conclusion: The difference in association between IFNα activity and IgG APL status between ancestral backgrounds supports differences in molecular pathogenesis. This may suggest B cell hyperactivity in the setting of type I IFN in African-Americans and could suggest ways to individualise therapy.

KW - antiphospholipid antibodies

KW - cytokines

KW - systemic lupus erythematosus

UR - http://www.scopus.com/inward/record.url?scp=85048089207&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85048089207&partnerID=8YFLogxK

U2 - 10.1136/lupus-2017-000246

DO - 10.1136/lupus-2017-000246

M3 - Article

AN - SCOPUS:85048089207

VL - 5

JO - Lupus Science and Medicine

JF - Lupus Science and Medicine

SN - 2053-8790

IS - 1

M1 - e000246

ER -