A cluster of type II interferon-regulated genes associates with disease activity in patients with systemic lupus erythematosus

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A cluster of type II interferon-regulated genes associates with disease activity in patients with systemic lupus erythematosus. / Siddiqi, Kanwal Zahid; Zinglersen, Amanda Hempel; Iversen, Katrine Kjær; Rasmussen, Niclas Stefan; Nielsen, Christoffer Tandrup; Jacobsen, Søren.

In: Journal of Autoimmunity, Vol. 132, 102869, 2022.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Siddiqi, KZ, Zinglersen, AH, Iversen, KK, Rasmussen, NS, Nielsen, CT & Jacobsen, S 2022, 'A cluster of type II interferon-regulated genes associates with disease activity in patients with systemic lupus erythematosus', Journal of Autoimmunity, vol. 132, 102869. https://doi.org/10.1016/j.jaut.2022.102869

APA

Siddiqi, K. Z., Zinglersen, A. H., Iversen, K. K., Rasmussen, N. S., Nielsen, C. T., & Jacobsen, S. (2022). A cluster of type II interferon-regulated genes associates with disease activity in patients with systemic lupus erythematosus. Journal of Autoimmunity, 132, [102869]. https://doi.org/10.1016/j.jaut.2022.102869

Vancouver

Siddiqi KZ, Zinglersen AH, Iversen KK, Rasmussen NS, Nielsen CT, Jacobsen S. A cluster of type II interferon-regulated genes associates with disease activity in patients with systemic lupus erythematosus. Journal of Autoimmunity. 2022;132. 102869. https://doi.org/10.1016/j.jaut.2022.102869

Author

Siddiqi, Kanwal Zahid ; Zinglersen, Amanda Hempel ; Iversen, Katrine Kjær ; Rasmussen, Niclas Stefan ; Nielsen, Christoffer Tandrup ; Jacobsen, Søren. / A cluster of type II interferon-regulated genes associates with disease activity in patients with systemic lupus erythematosus. In: Journal of Autoimmunity. 2022 ; Vol. 132.

Bibtex

@article{7e3e9d8e65584a64bc311798b1c274c1,
title = "A cluster of type II interferon-regulated genes associates with disease activity in patients with systemic lupus erythematosus",
abstract = "Upregulation of interferon-regulated genes (IRGs), denoted IFN signature, in peripheral blood has been used as an indirect measure of IFN pathway activation in patients with systemic lupus erythematosus (SLE). However, it has not been determined, which IFN signatures that optimally reflect clinical disease activity. In this study, we determined an IFN signature based on the expression of 128 IRGs in whole blood from 34 SLE patients in a cross-sectional (CS) study, 11 with active lupus nephritis followed longitudinally (LS) and 15 healthy controls. Blood samples were collected in PAXgene tubes and RNA was extracted and purified using a PAXgene blood RNA kit (Qiagen). Gene expression was measured using the NanoString nCounter Gene Expression platform. The CS SLE patients with higher disease activity displayed thrice as many upregulated IRGs (n = 46) as the rest. These IRGs clustered in three groups, consisting of IRGs known to be predominantly stimulated by type I (gene cluster K1) and type II (gene clusters K2 and 3) IFNs. SLEDAI-2K scores associated with the K2 and K3 gene scores (β = 0.372 and β = 0.419, both p < 0.015) but not with K1. In the longitudinal study, the mean SLEDAI-2K score decreased after an average follow-up of 360 days (β = −2.08, P = 5.09 × 10−12). The mean K1, K2 and K3 gene scores did not change over time, however longitudinal changes in SLEDAI-2K and K3 scores were associated (β = 0.814, p = 0.007). This study validates the presence of type I IRG subsets that do not associate with disease activity in SLE patients. The novel finding in this study is the association between a type II IRG subset and disease activity. Both findings may have significant implications for choosing IRGs defining clinically relevant IFN signatures.",
keywords = "Disease activity, Interferon signature, Interferon-regulated genes, SLEDAI-2K, Systemic lupus erythematosus",
author = "Siddiqi, {Kanwal Zahid} and Zinglersen, {Amanda Hempel} and Iversen, {Katrine Kj{\ae}r} and Rasmussen, {Niclas Stefan} and Nielsen, {Christoffer Tandrup} and S{\o}ren Jacobsen",
note = "Publisher Copyright: {\textcopyright} 2022 Elsevier Ltd",
year = "2022",
doi = "10.1016/j.jaut.2022.102869",
language = "English",
volume = "132",
journal = "Journal of Autoimmunity",
issn = "0896-8411",
publisher = "Academic Press",

}

RIS

TY - JOUR

T1 - A cluster of type II interferon-regulated genes associates with disease activity in patients with systemic lupus erythematosus

AU - Siddiqi, Kanwal Zahid

AU - Zinglersen, Amanda Hempel

AU - Iversen, Katrine Kjær

AU - Rasmussen, Niclas Stefan

AU - Nielsen, Christoffer Tandrup

AU - Jacobsen, Søren

N1 - Publisher Copyright: © 2022 Elsevier Ltd

PY - 2022

Y1 - 2022

N2 - Upregulation of interferon-regulated genes (IRGs), denoted IFN signature, in peripheral blood has been used as an indirect measure of IFN pathway activation in patients with systemic lupus erythematosus (SLE). However, it has not been determined, which IFN signatures that optimally reflect clinical disease activity. In this study, we determined an IFN signature based on the expression of 128 IRGs in whole blood from 34 SLE patients in a cross-sectional (CS) study, 11 with active lupus nephritis followed longitudinally (LS) and 15 healthy controls. Blood samples were collected in PAXgene tubes and RNA was extracted and purified using a PAXgene blood RNA kit (Qiagen). Gene expression was measured using the NanoString nCounter Gene Expression platform. The CS SLE patients with higher disease activity displayed thrice as many upregulated IRGs (n = 46) as the rest. These IRGs clustered in three groups, consisting of IRGs known to be predominantly stimulated by type I (gene cluster K1) and type II (gene clusters K2 and 3) IFNs. SLEDAI-2K scores associated with the K2 and K3 gene scores (β = 0.372 and β = 0.419, both p < 0.015) but not with K1. In the longitudinal study, the mean SLEDAI-2K score decreased after an average follow-up of 360 days (β = −2.08, P = 5.09 × 10−12). The mean K1, K2 and K3 gene scores did not change over time, however longitudinal changes in SLEDAI-2K and K3 scores were associated (β = 0.814, p = 0.007). This study validates the presence of type I IRG subsets that do not associate with disease activity in SLE patients. The novel finding in this study is the association between a type II IRG subset and disease activity. Both findings may have significant implications for choosing IRGs defining clinically relevant IFN signatures.

AB - Upregulation of interferon-regulated genes (IRGs), denoted IFN signature, in peripheral blood has been used as an indirect measure of IFN pathway activation in patients with systemic lupus erythematosus (SLE). However, it has not been determined, which IFN signatures that optimally reflect clinical disease activity. In this study, we determined an IFN signature based on the expression of 128 IRGs in whole blood from 34 SLE patients in a cross-sectional (CS) study, 11 with active lupus nephritis followed longitudinally (LS) and 15 healthy controls. Blood samples were collected in PAXgene tubes and RNA was extracted and purified using a PAXgene blood RNA kit (Qiagen). Gene expression was measured using the NanoString nCounter Gene Expression platform. The CS SLE patients with higher disease activity displayed thrice as many upregulated IRGs (n = 46) as the rest. These IRGs clustered in three groups, consisting of IRGs known to be predominantly stimulated by type I (gene cluster K1) and type II (gene clusters K2 and 3) IFNs. SLEDAI-2K scores associated with the K2 and K3 gene scores (β = 0.372 and β = 0.419, both p < 0.015) but not with K1. In the longitudinal study, the mean SLEDAI-2K score decreased after an average follow-up of 360 days (β = −2.08, P = 5.09 × 10−12). The mean K1, K2 and K3 gene scores did not change over time, however longitudinal changes in SLEDAI-2K and K3 scores were associated (β = 0.814, p = 0.007). This study validates the presence of type I IRG subsets that do not associate with disease activity in SLE patients. The novel finding in this study is the association between a type II IRG subset and disease activity. Both findings may have significant implications for choosing IRGs defining clinically relevant IFN signatures.

KW - Disease activity

KW - Interferon signature

KW - Interferon-regulated genes

KW - SLEDAI-2K

KW - Systemic lupus erythematosus

U2 - 10.1016/j.jaut.2022.102869

DO - 10.1016/j.jaut.2022.102869

M3 - Journal article

C2 - 35933792

AN - SCOPUS:85135506898

VL - 132

JO - Journal of Autoimmunity

JF - Journal of Autoimmunity

SN - 0896-8411

M1 - 102869

ER -

ID: 328425666