Title | Personalized Immunomonitoring Uncovers Molecular Networks that Stratify Lupus Patients. |
Publication Type | Journal Article |
Year of Publication | 2016 |
Authors | 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, Banchereau J, Rossello-Urgell J, Wright T, Pascual V |
Journal | Cell |
Volume | 165 |
Issue | 3 |
Pagination | 551-65 |
Date Published | 2016 Apr 21 |
ISSN | 1097-4172 |
Keywords | Adolescent, Child, Female, Humans, Longitudinal Studies, Lupus Erythematosus, Systemic, Lupus Nephritis, Neutrophils, Polymorphism, Single Nucleotide, Precision Medicine, Transcriptome |
Abstract | 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. |
DOI | 10.1016/j.cell.2016.03.008 |
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Alternate Journal | Cell |
PubMed ID | 27040498 |
PubMed Central ID | PMC5426482 |
Grant List | P50 AR054083 / AR / NIAMS NIH HHS / United States P50 AR070594 / AR / NIAMS NIH HHS / United States U19 AI082715 / AI / NIAID NIH HHS / United States |