Lupus Patients’ Molecular Signature May Allow for Personalized Therapies, Scientists Say

Immuno-molecular profiling of systemic lupus erythematosus (SLE) patients has uncovered a personalized molecular signature underlying disease activity that may help scientists develop new tailored therapeutics.

The study, “Personalized Immunomonitoring Uncovers Molecular Networks that Stratify Lupus Patients,” was recently published in the journal Cell.

SLE, which predominantly affects young women, is a severe autoimmune disease that currently has no cure. The disease is characterized by production of autoantibodies (antibodies that react against an individual’s own tissue) including those against double-stranded DNA (dsDNA), ribonucleoproteins (RNPs), cardiolipin, and phospholipids.

Rather than a continuous development of disease severity, SLE is characterized by periods of remission and flares that over time lead to cumulative damage. Therefore, disease manifestations are clinically heterogeneous and a therapeutic solution will require personalized treatments according to each patient’s disease-underlying mechanisms.

SLE patients carry unique blood transcriptional signatures linked to type I interferon (IFN) and granulocytes. Preliminary studies have showed that a patient’s transcriptome signature can be used to determine disease activity. However, these initial studies were performed with a limited number of cohorts and focused specifically on IFN-induced transcripts.

Researchers at the Baylor Institute for Immunology Research in Dallas, Texas, investigated SLE’s molecular heterogeneity and performed a transcriptome screen in 924 longitudinal blood samples from 158 pediatric patients. They used several models to account and incorporate repeated measurements, demographics, treatment, disease activity, and nephritis class.

Researchers identified and confirmed a prevalent IFN signature and identified a plasmablast signature as the most robust biomarker of disease activity. Moreover, they detected a gradual enrichment of immune signatures during disease progression, and linked neutrophils (the most abundant type of granulocytes, white blood cells) to active nephritis (inflammation of the kidney, commonly observed in SLE patients). Most importantly, researchers discovered that monitoring patients’ immune profile — personalized immunomonitoring — allowed for a stratification according to disease activity into seven major groups.

By performing personalized immunoprofiling in a large group of patients, researchers uncovered the molecular heterogeneity of SLE, identifying molecular signatures correlated with disease activity. These may improve the outcome of clinical trials in SLE by fine-tuning trial design, eventually leading to tailored therapies in lupus and other autoimmune diseases.