Personalized Immunomonitoring Uncovers Molecular Networks that Stratify Lupus Patients.

TitlePersonalized Immunomonitoring Uncovers Molecular Networks that Stratify Lupus Patients.
Publication TypeJournal Article
Year of Publication2016
AuthorsBanchereau 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, Banchereau J, Rossello-Urgell J, Wright T, Pascual V
Date Published2016 Apr 21
KeywordsAdolescent, Child, Female, Humans, Longitudinal Studies, Lupus Erythematosus, Systemic, Lupus Nephritis, Neutrophils, Polymorphism, Single Nucleotide, Precision Medicine, Transcriptome

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. PAPERCLIP.

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Alternate JournalCell
PubMed ID27040498
PubMed Central IDPMC5426482
Grant ListP50 AR054083 / AR / NIAMS NIH HHS / United States
P50 AR070594 / AR / NIAMS NIH HHS / United States
U19 AI082715 / AI / NIAID NIH HHS / United States

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