Personalized Immunomonitoring Uncovers Molecular Networks that Stratify Lupus Patients

Romain Banchereau, Seunghee Hong, Brandi Cantarel, Nicole Baldwin, Jeanine Baisch, Michelle Edens, Alma Martina Cepika, Peter Acs, Jacob Turner, Esperanza Anguiano, Parvathi Vinod, Shaheen Kahn, Gerlinde Obermoser, Derek Blankenship, Edward Wakeland, Lorien Nassi, Alisa Gotte, Marilynn Punaro, Yong Jun Liu, Jacques BanchereauJose Rossello-Urgell, Tracey Wright, Virginia Pascual

Research output: Contribution to journalArticle

171 Scopus citations

Abstract

Summary Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by loss of tolerance to nucleic acids and highly diverse clinical manifestations. To assess its molecular heterogeneity, we longitudinally profiled the blood transcriptome of 158 pediatric patients. Using mixed models accounting for repeated measurements, demographics, treatment, disease activity (DA), and nephritis class, we confirmed a prevalent IFN signature and identified a plasmablast signature as the most robust biomarker of DA. We detected gradual enrichment of neutrophil transcripts during progression to active nephritis and distinct signatures in response to treatment in different nephritis subclasses. Importantly, personalized immunomonitoring uncovered individual correlates of disease activity that enabled patient stratification into seven groups, supported by patient genotypes. Our study uncovers the molecular heterogeneity of SLE and provides an explanation for the failure of clinical trials. This approach may improve trial design and implementation of tailored therapies in genetically and clinically complex autoimmune diseases.

Original languageEnglish (US)
Pages (from-to)551-565
Number of pages15
JournalCell
Volume165
Issue number3
DOIs
StatePublished - Apr 21 2016

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Banchereau, R., Hong, S., Cantarel, B., Baldwin, N., Baisch, J., Edens, M., Cepika, A. M., Acs, P., Turner, J., Anguiano, E., Vinod, P., Kahn, S., Obermoser, G., Blankenship, D., Wakeland, E., Nassi, L., Gotte, A., Punaro, M., Liu, Y. J., ... Pascual, V. (2016). Personalized Immunomonitoring Uncovers Molecular Networks that Stratify Lupus Patients. Cell, 165(3), 551-565. https://doi.org/10.1016/j.cell.2016.03.008