Personalized Immunomonitoring Uncovers Molecular Networks that Stratify Lupus Patients.
Document Type
Article
Publication Date
4-21-2016
JAX Source
Cell 2016 Apr 21; 165(4):551-65.
Volume
165
Issue
3
First Page
551
Last Page
565
ISSN
1097-4172
PMID
27040498
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. Cell 2016 Apr 21; 165(4):551-65.
Recommended Citation
Banchereau R,
Hong S,
Cantarel B,
Baldwin N,
Baisch J,
Edens M,
Cepika A,
Acs P,
Turner J,
Anguiano E,
Vinod P,
Kahn S,
Obermoser G,
Blankenship D,
Wakeland E,
Nassi L,
Gotte A,
Punaro M,
Liu Y,
Banchereau J,
Rossello-Urgell J,
Wright T,
Pascual V.
Personalized Immunomonitoring Uncovers Molecular Networks that Stratify Lupus Patients. Cell 2016 Apr 21; 165(4):551-65.