TY - JOUR
T1 - Type I Interferon Predicts an Alternate Immune System Phenotype in Systemic Lupus Erythematosus
AU - Thanarajasingam, Uma
AU - Muppirala, Anoohya N.
AU - Jensen, Mark A.
AU - Ghodke-Puranik, Yogita
AU - Dorschner, Jessica M.
AU - Vsetecka, Danielle M.
AU - Amin, Shreyasee
AU - Makol, Ashima
AU - Ernste, Floranne
AU - Osborn, Thomas
AU - Moder, Kevin
AU - Chowdhary, Vaidehi
AU - Niewold, Timothy B.
N1 - Publisher Copyright:
© 2019 The Authors. ACR Open Rheumatology published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology.
PY - 2019/10/1
Y1 - 2019/10/1
N2 - Objective: Type I interferon (IFN) is important to systemic lupus erythematosus (SLE) pathogenesis, but it is not clear how chronic elevations in IFN alter immune function. We compared cytokine responses after whole blood stimulation with Toll-like receptor (TLR) agonists in high- and low-IFN SLE patient subgroups. Methods: SLE patients and nonautoimmune controls were recruited, and SLE patients were categorized as either high or low IFN. Whole blood was dispensed into tubes coated with lipopolysaccharide (LPS), oligonucleotides with cytosine-guanine repeats, Resiquimod, IFN-α, and IFN-α + LPS. Cytokine production in patient sera and after whole blood TLR stimulation was measured by multiplex assay, and type I IFN was assessed using a functional assay. Results: Circulating plasmacytoid dendritic cell numbers were specifically reduced in high-IFN SLE patients and not in low-IFN SLE patients. In serum, we observed that the correlations between cytokines in serum differed to a much greater degree between the high- and low-IFN groups (P < 0.0001) than the absolute cytokine levels differed between these same groups. In stimulated conditions, the high-IFN patients had less cytokine production in response to TLR ligation than the low-IFN SLE patients. LPS produced the most diverse response, and a number of interactions between type I IFN and LPS were observed. Conclusion: We find striking differences in resting and stimulated cytokine patterns in high- vs. low-IFN SLE patients, which supports the biological importance of these patient subsets. These data could inform personalized treatment approaches and the pathogenesis of SLE flare following infection.
AB - Objective: Type I interferon (IFN) is important to systemic lupus erythematosus (SLE) pathogenesis, but it is not clear how chronic elevations in IFN alter immune function. We compared cytokine responses after whole blood stimulation with Toll-like receptor (TLR) agonists in high- and low-IFN SLE patient subgroups. Methods: SLE patients and nonautoimmune controls were recruited, and SLE patients were categorized as either high or low IFN. Whole blood was dispensed into tubes coated with lipopolysaccharide (LPS), oligonucleotides with cytosine-guanine repeats, Resiquimod, IFN-α, and IFN-α + LPS. Cytokine production in patient sera and after whole blood TLR stimulation was measured by multiplex assay, and type I IFN was assessed using a functional assay. Results: Circulating plasmacytoid dendritic cell numbers were specifically reduced in high-IFN SLE patients and not in low-IFN SLE patients. In serum, we observed that the correlations between cytokines in serum differed to a much greater degree between the high- and low-IFN groups (P < 0.0001) than the absolute cytokine levels differed between these same groups. In stimulated conditions, the high-IFN patients had less cytokine production in response to TLR ligation than the low-IFN SLE patients. LPS produced the most diverse response, and a number of interactions between type I IFN and LPS were observed. Conclusion: We find striking differences in resting and stimulated cytokine patterns in high- vs. low-IFN SLE patients, which supports the biological importance of these patient subsets. These data could inform personalized treatment approaches and the pathogenesis of SLE flare following infection.
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U2 - 10.1002/acr2.11073
DO - 10.1002/acr2.11073
M3 - Article
AN - SCOPUS:85088474187
SN - 2578-5745
VL - 1
SP - 499
EP - 506
JO - ACR Open Rheumatology
JF - ACR Open Rheumatology
IS - 8
ER -