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Cell. 2016 Apr 21;165(3):551-65. doi: 10.1016/j.cell.2016.03.008. Epub 2016 Mar 31.

Personalized Immunomonitoring Uncovers Molecular Networks that Stratify Lupus Patients.

Author information

1
Baylor Institute for Immunology Research, Dallas, TX 75204, USA.
2
UT Southwestern Medical Center, Dallas, TX 75235, USA.
3
UT Southwestern Medical Center, Dallas, TX 75235, USA; Texas Scottish Rite Hospital for Children, Dallas, TX 75219, USA.
4
UT Southwestern Medical Center, Dallas, TX 75235, USA; Texas Scottish Rite Hospital for Children, Dallas, TX 75219, USA; Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
5
Baylor Institute for Immunology Research, Dallas, TX 75204, USA; MedImmune, Gaithersburg, MD 20878, USA.
6
The Jackson Laboratory for Genomic Medicine, Farmington, CT 06030, USA.
7
Baylor Institute for Immunology Research, Dallas, TX 75204, USA; Texas Scottish Rite Hospital for Children, Dallas, TX 75219, USA. Electronic address: virginia.pascual@bswhealth.org.

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.

PMID:
27040498
PMCID:
PMC5426482
DOI:
10.1016/j.cell.2016.03.008
[Indexed for MEDLINE]
Free PMC Article

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