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Modular transcriptional repertoire analyses identify a blood neutrophil signature as a candidate biomarker for lupus nephritis.
Rheumatology (Oxford) 2017; 56(3):477-487R

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.

Conclusion

Modular neutrophil signature could be a biomarker for stratifying LN risk and for monitoring its response to treatment.

Trial registration

ClinicalTrials.gov, http://clinicaltrials.gov , NCT00920114.

Authors+Show Affiliations

Department of Nephrology, Aix-Marseille University, AP-HM, Hôpital Conception, UMR_S 1076, Vascular Research Center of Marseille, Marseille, France.Systems Immunology Department, Benaroya Research Institute, Seattle.Department of Nephrology, Aix-Marseille University, AP-HM, Hôpital Conception, UMR_S 1076, Vascular Research Center of Marseille, Marseille, France.Systems Immunology Department, Benaroya Research Institute, Seattle.Systems Immunology Department, Benaroya Research Institute, Seattle.Department of Nephrology, Aix-Marseille University, AP-HM, Hôpital Conception, UMR_S 1076, Vascular Research Center of Marseille, Marseille, France.Department of Nephrology, Aix-Marseille University, AP-HM, Hôpital Conception, UMR_S 1076, Vascular Research Center of Marseille, Marseille, France.Immunology, Baylor Institute for Immunology Research, Dallas, TX, USA.Systems Biology Department, Sidra Medical and Research Center, Doha, Qatar.Department of Internal Medicine, Hôpital Européen, Marseille, France.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

28031441

Citation

Jourde-Chiche, Noémie, et al. "Modular Transcriptional Repertoire Analyses Identify a Blood Neutrophil Signature as a Candidate Biomarker for Lupus Nephritis." Rheumatology (Oxford, England), vol. 56, no. 3, 2017, pp. 477-487.
Jourde-Chiche N, Whalen E, Gondouin B, et al. Modular transcriptional repertoire analyses identify a blood neutrophil signature as a candidate biomarker for lupus nephritis. Rheumatology (Oxford). 2017;56(3):477-487.
Jourde-Chiche, N., 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 (Oxford, England), 56(3), pp. 477-487. doi:10.1093/rheumatology/kew439.
Jourde-Chiche N, et al. Modular Transcriptional Repertoire Analyses Identify a Blood Neutrophil Signature as a Candidate Biomarker for Lupus Nephritis. Rheumatology (Oxford). 2017 03 1;56(3):477-487. PubMed PMID: 28031441.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Modular transcriptional repertoire analyses identify a blood neutrophil signature as a candidate biomarker for lupus nephritis. AU - Jourde-Chiche,Noémie, AU - Whalen,Elizabeth, AU - Gondouin,Bertrand, AU - Speake,Cate, AU - Gersuk,Vivian, AU - Dussol,Bertrand, AU - Burtey,Stephane, AU - Pascual,Virginia, AU - Chaussabel,Damien, AU - Chiche,Laurent, PY - 2016/04/02/received PY - 2016/12/30/pubmed PY - 2017/6/21/medline PY - 2016/12/30/entrez KW - biomarkers KW - gene expression KW - lupus nephritis KW - neutrophil KW - systemic lupus erythematosus SP - 477 EP - 487 JF - Rheumatology (Oxford, England) JO - Rheumatology (Oxford) VL - 56 IS - 3 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. Conclusion: Modular neutrophil signature could be a biomarker for stratifying LN risk and for monitoring its response to treatment. Trial registration: ClinicalTrials.gov, http://clinicaltrials.gov , NCT00920114. SN - 1462-0332 UR - https://www.unboundmedicine.com/medline/citation/28031441/Modular_transcriptional_repertoire_analyses_identify_a_blood_neutrophil_signature_as_a_candidate_biomarker_for_lupus_nephritis_ L2 - https://academic.oup.com/rheumatology/article-lookup/doi/10.1093/rheumatology/kew439 DB - PRIME DP - Unbound Medicine ER -