Identification of highly active systemic lupus erythematosus by combined type I interferon and neutrophil gene scores vs classical serologic markers.
Publisher DOI
PubMed ID
32375176
Abstract
OBJECTIVES
In SLE, heterogeneous clinical expression and activity may reflect diverse pathogenic and/or effector mechanisms. We investigated SLE heterogeneity by assessing the expression of three gene sets representative of type I IFN (IFN-I), polymorphonuclear neutrophil (PMN) and plasmablast (PB) signatures in a well-characterized, multidisciplinary cohort of SLE patients. We further assessed whether individual gene products could be representative of these three signatures.
METHODS
Whole blood, serum and clinical data were obtained from 140 SLE individuals. Gene expression was assessed by NanoString technology, using a panel of 37 probes to compute six IFN-I, one PMN and one PB scores. Protein levels were measured by ELISA.
RESULTS
Depending on the score, 45-50% of SLE individuals showed high IFN-I gene expression. All six IFN-I scores were significantly associated with active skin involvement, and two of six were associated with arthritis. IFN-induced Mx1 protein (MX1) level was correlated with IFN-I score (P < 0.0001) and associated with a similar clinical phenotype. In all, 25% of SLE individuals showed high PMN gene expression, associated with SLE fever, serositis, leukopoenia and glucocorticoid use. PB gene expression was highly affected by immunosuppressant agents, with no association with SLE features. Combined IFN-I and PMN gene scores were significantly associated with high disease activity and outperformed anti-dsDNA and anti-C1q autoantibody and complement levels for predicting SLE activity.
CONCLUSION
IFN-I and PMN gene scores segregate with distinct SLE clinical features, and their combination may identify high disease activity. MX1 protein level performed similar to IFN-I gene expression.
In SLE, heterogeneous clinical expression and activity may reflect diverse pathogenic and/or effector mechanisms. We investigated SLE heterogeneity by assessing the expression of three gene sets representative of type I IFN (IFN-I), polymorphonuclear neutrophil (PMN) and plasmablast (PB) signatures in a well-characterized, multidisciplinary cohort of SLE patients. We further assessed whether individual gene products could be representative of these three signatures.
METHODS
Whole blood, serum and clinical data were obtained from 140 SLE individuals. Gene expression was assessed by NanoString technology, using a panel of 37 probes to compute six IFN-I, one PMN and one PB scores. Protein levels were measured by ELISA.
RESULTS
Depending on the score, 45-50% of SLE individuals showed high IFN-I gene expression. All six IFN-I scores were significantly associated with active skin involvement, and two of six were associated with arthritis. IFN-induced Mx1 protein (MX1) level was correlated with IFN-I score (P < 0.0001) and associated with a similar clinical phenotype. In all, 25% of SLE individuals showed high PMN gene expression, associated with SLE fever, serositis, leukopoenia and glucocorticoid use. PB gene expression was highly affected by immunosuppressant agents, with no association with SLE features. Combined IFN-I and PMN gene scores were significantly associated with high disease activity and outperformed anti-dsDNA and anti-C1q autoantibody and complement levels for predicting SLE activity.
CONCLUSION
IFN-I and PMN gene scores segregate with distinct SLE clinical features, and their combination may identify high disease activity. MX1 protein level performed similar to IFN-I gene expression.
Date Issued
2020-11-01
Publication Type
Article
Subject(s)
Subjects
gene expression polymorphonuclear cells score systemic lupus erythematosus type-I interferon
Language(s)
en
Author(s)
Chasset, François | |
Ribi, Camillo | |
Trendelenburg, Marten | |
Roux-Lombard, Pascale | |
Courvoisier, Delphine S | |
Chizzolini, Carlo |
Additional Credits
Journal
Rheumatology
Publisher
Oxford University Press
ISSN
1462-0324
Access(Rights)
restricted