title: Modular transcriptional repertoire analyses identify a blood neutrophil signature as a candidate biomarker for lupus nephritis.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  Modular neutrophil signature could be a biomarker for stratifying LN risk and for monitoring its response to treatment.
  
  
  
  ClinicalTrials.gov, http://clinicaltrials.gov , NCT00920114.
authors.affiliation: Department of Nephrology, Aix-Marseille University, AP-HM, Hôpital Conception, UMR_S 1076, Vascular Research Center of Marseille, Marseille, France.
authors.forename: Noémie
authors.initials: N
authors.lastname: Jourde-Chiche
authors.affiliation: Systems Immunology Department, Benaroya Research Institute, Seattle.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Whalen
authors.affiliation: Department of Nephrology, Aix-Marseille University, AP-HM, Hôpital Conception, UMR_S 1076, Vascular Research Center of Marseille, Marseille, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Gondouin
authors.affiliation: Systems Immunology Department, Benaroya Research Institute, Seattle.
authors.forename: Cate
authors.initials: C
authors.lastname: Speake
authors.affiliation: Systems Immunology Department, Benaroya Research Institute, Seattle.
authors.forename: Vivian
authors.initials: V
authors.lastname: Gersuk
authors.affiliation: Department of Nephrology, Aix-Marseille University, AP-HM, Hôpital Conception, UMR_S 1076, Vascular Research Center of Marseille, Marseille, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Dussol
authors.affiliation: Department of Nephrology, Aix-Marseille University, AP-HM, Hôpital Conception, UMR_S 1076, Vascular Research Center of Marseille, Marseille, France.
authors.forename: Stephane
authors.initials: S
authors.lastname: Burtey
authors.affiliation: Immunology, Baylor Institute for Immunology Research, Dallas, TX, USA.
authors.forename: Virginia
authors.initials: V
authors.lastname: Pascual
authors.affiliation: Systems Biology Department, Sidra Medical and Research Center, Doha, Qatar.
authors.forename: Damien
authors.initials: D
authors.lastname: Chaussabel
authors.affiliation: Department of Internal Medicine, Hôpital Européen, Marseille, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Chiche
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000235:genetics / Q000276:immunology; D000974:Antibodies, Antinuclear / Q000276:immunology; D016022:Case-Control Studies; D004247:DNA / Q000276:immunology; D018450:Disease Progression; D005260:Female; D005921:Glomerulonephritis / Q000235:genetics; D006801:Humans; D007676:Kidney Failure, Chronic / Q000209:etiology / Q000235:genetics* / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000150:complications; D008181:Lupus Nephritis / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology; D008297:Male; D009404:Nephrotic Syndrome / Q000209:etiology / Q000235:genetics* / Q000276:immunology; D009504:Neutrophils / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism*; D018805:Sepsis / Q000235:genetics / Q000276:immunology; D012720:Severity of Illness Index; D059467:Transcriptome; D015854:Up-Regulation
chemical_list: D000305:Adrenal Cortex Hormones; D000974:Antibodies, Antinuclear; D012333:RNA, Messenger; D004247:DNA
keywords: biomarkers; gene expression; lupus nephritis; neutrophil; systemic lupus erythematosus