Modular transcriptional repertoire analyses identify a blood neutrophil signature as a candidate biomarker for lupus nephritis

Noé mie Jourde-Chiche, Elizabeth Whalen, Bertrand Gondouin, Cate Speake, Vivian Gersuk, Bertrand Dussol, Stephane Burtey, Virginia Pascual, Damien J. Chaussabel, Laurent Chiche

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Objective. LN is a severe complication of SLE. Non-invasive biomarkers are needed for identifying patients at risk of a renal flare, for differentiating proliferative from non-proliferative forms and for assessing prognoses for LN. Methods. We assessed the link between blood transcriptional signatures and LN using blood samples from patients with biopsy-proven LN, extra-renal SLE flares or quiescent SLE. Healthy controls, and control patients with glomerular diseases or bacterial sepsis were included. Modular repertoire analyses from microarray data were confirmed by PCR. Results. A modular neutrophil signature (upregulation of module M5.15) was present in 65% of SLE patients and was strongly associated with LN. M5.15 activity was stronger in LN than in extra-renal flares (88 vs 17%). M5.15 was neither correlated to IFN modules, nor to SLEDAI or anti-dsDNA antibodies, but moderately to CS dose. M5.15 activity was associated with severity of LN, was stronger when proliferative, and decreased in patients responding to treatment. M5.15 activation was not caused by higher CS dose because it correlated only moderately to neutrophil count and was also observed among quiescent patients. Among quiescent patients, those with a past history of LN had higher M5.15 activity (50 vs 8%). M5.15 activation was present in patients with bacterial sepsis or ANCA-associated vasculitis, but not in patients with other glomerular diseases. Overall, M5.15 activation was associated with past, present or future flares of LN.

Original languageEnglish
Article numberkew439
Pages (from-to)477-487
Number of pages11
JournalRheumatology (United Kingdom)
Volume56
Issue number3
DOIs
Publication statusPublished - 1 Mar 2017

Fingerprint

Lupus Nephritis
Neutrophils
Biomarkers
Kidney
Sepsis
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
Microarray Analysis
Anti-Idiotypic Antibodies
Up-Regulation
Biopsy
Polymerase Chain Reaction

Keywords

  • Biomarkers
  • Gene expression
  • Lupus nephritis
  • Neutrophil
  • Systemic lupus erythematosus

ASJC Scopus subject areas

  • Rheumatology
  • Pharmacology (medical)

Cite this

Jourde-Chiche, N. M., Whalen, E., Gondouin, B., Speake, C., Gersuk, V., Dussol, B., ... Chiche, L. (2017). Modular transcriptional repertoire analyses identify a blood neutrophil signature as a candidate biomarker for lupus nephritis. Rheumatology (United Kingdom), 56(3), 477-487. [kew439]. https://doi.org/10.1093/rheumatology/kew439

Modular transcriptional repertoire analyses identify a blood neutrophil signature as a candidate biomarker for lupus nephritis. / Jourde-Chiche, Noé mie; Whalen, Elizabeth; Gondouin, Bertrand; Speake, Cate; Gersuk, Vivian; Dussol, Bertrand; Burtey, Stephane; Pascual, Virginia; Chaussabel, Damien J.; Chiche, Laurent.

In: Rheumatology (United Kingdom), Vol. 56, No. 3, kew439, 01.03.2017, p. 477-487.

Research output: Contribution to journalArticle

Jourde-Chiche, NM, Whalen, E, Gondouin, B, Speake, C, Gersuk, V, Dussol, B, Burtey, S, Pascual, V, Chaussabel, DJ & Chiche, L 2017, 'Modular transcriptional repertoire analyses identify a blood neutrophil signature as a candidate biomarker for lupus nephritis', Rheumatology (United Kingdom), vol. 56, no. 3, kew439, pp. 477-487. https://doi.org/10.1093/rheumatology/kew439
Jourde-Chiche, Noé mie ; Whalen, Elizabeth ; Gondouin, Bertrand ; Speake, Cate ; Gersuk, Vivian ; Dussol, Bertrand ; Burtey, Stephane ; Pascual, Virginia ; Chaussabel, Damien J. ; Chiche, Laurent. / Modular transcriptional repertoire analyses identify a blood neutrophil signature as a candidate biomarker for lupus nephritis. In: Rheumatology (United Kingdom). 2017 ; Vol. 56, No. 3. pp. 477-487.
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abstract = "Objective. LN is a severe complication of SLE. Non-invasive biomarkers are needed for identifying patients at risk of a renal flare, for differentiating proliferative from non-proliferative forms and for assessing prognoses for LN. Methods. We assessed the link between blood transcriptional signatures and LN using blood samples from patients with biopsy-proven LN, extra-renal SLE flares or quiescent SLE. Healthy controls, and control patients with glomerular diseases or bacterial sepsis were included. Modular repertoire analyses from microarray data were confirmed by PCR. Results. A modular neutrophil signature (upregulation of module M5.15) was present in 65{\%} of SLE patients and was strongly associated with LN. M5.15 activity was stronger in LN than in extra-renal flares (88 vs 17{\%}). M5.15 was neither correlated to IFN modules, nor to SLEDAI or anti-dsDNA antibodies, but moderately to CS dose. M5.15 activity was associated with severity of LN, was stronger when proliferative, and decreased in patients responding to treatment. M5.15 activation was not caused by higher CS dose because it correlated only moderately to neutrophil count and was also observed among quiescent patients. Among quiescent patients, those with a past history of LN had higher M5.15 activity (50 vs 8{\%}). M5.15 activation was present in patients with bacterial sepsis or ANCA-associated vasculitis, but not in patients with other glomerular diseases. Overall, M5.15 activation was associated with past, present or future flares of LN.",
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AU - Gersuk, Vivian

AU - Dussol, Bertrand

AU - Burtey, Stephane

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N2 - Objective. LN is a severe complication of SLE. Non-invasive biomarkers are needed for identifying patients at risk of a renal flare, for differentiating proliferative from non-proliferative forms and for assessing prognoses for LN. Methods. We assessed the link between blood transcriptional signatures and LN using blood samples from patients with biopsy-proven LN, extra-renal SLE flares or quiescent SLE. Healthy controls, and control patients with glomerular diseases or bacterial sepsis were included. Modular repertoire analyses from microarray data were confirmed by PCR. Results. A modular neutrophil signature (upregulation of module M5.15) was present in 65% of SLE patients and was strongly associated with LN. M5.15 activity was stronger in LN than in extra-renal flares (88 vs 17%). M5.15 was neither correlated to IFN modules, nor to SLEDAI or anti-dsDNA antibodies, but moderately to CS dose. M5.15 activity was associated with severity of LN, was stronger when proliferative, and decreased in patients responding to treatment. M5.15 activation was not caused by higher CS dose because it correlated only moderately to neutrophil count and was also observed among quiescent patients. Among quiescent patients, those with a past history of LN had higher M5.15 activity (50 vs 8%). M5.15 activation was present in patients with bacterial sepsis or ANCA-associated vasculitis, but not in patients with other glomerular diseases. Overall, M5.15 activation was associated with past, present or future flares of LN.

AB - Objective. LN is a severe complication of SLE. Non-invasive biomarkers are needed for identifying patients at risk of a renal flare, for differentiating proliferative from non-proliferative forms and for assessing prognoses for LN. Methods. We assessed the link between blood transcriptional signatures and LN using blood samples from patients with biopsy-proven LN, extra-renal SLE flares or quiescent SLE. Healthy controls, and control patients with glomerular diseases or bacterial sepsis were included. Modular repertoire analyses from microarray data were confirmed by PCR. Results. A modular neutrophil signature (upregulation of module M5.15) was present in 65% of SLE patients and was strongly associated with LN. M5.15 activity was stronger in LN than in extra-renal flares (88 vs 17%). M5.15 was neither correlated to IFN modules, nor to SLEDAI or anti-dsDNA antibodies, but moderately to CS dose. M5.15 activity was associated with severity of LN, was stronger when proliferative, and decreased in patients responding to treatment. M5.15 activation was not caused by higher CS dose because it correlated only moderately to neutrophil count and was also observed among quiescent patients. Among quiescent patients, those with a past history of LN had higher M5.15 activity (50 vs 8%). M5.15 activation was present in patients with bacterial sepsis or ANCA-associated vasculitis, but not in patients with other glomerular diseases. Overall, M5.15 activation was associated with past, present or future flares of LN.

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