Understanding Molecular Diversity of Lupus Could Personalize Treatment Approach, Improve Clinical Trials

In a landmark study, principal researcher Virginia Pascual at the Baylor Institute for Immunology Research, and colleagues, investigated the molecular diversity of lupus and found that a personalized immuno-monitoring approach allows for classification of patients into specific disease groups. Researchers believe these results may explain why lupus clinical trials have a low success rate while allowing improvements in clinical trials and designing treatments that are personalized for patients.

The research paper, “Personalized Immunomonitoring Uncovers Molecular Networks that Stratify Lupus Patients,” was recently published online in Cell.

Systemic lupus erythematosus (SLE), a chronic autoimmune disease, is especially difficult to diagnose mainly because there is no single test that can accurately detect the disease and to the great diversity of clinical manifestations and genetic profiles observed in patients. The heterogeneity of lupus also contributes to the limited success of clinical trials designed to discover new treatments.

Pascual and her team wanted to understand this molecular diversity to provide tools for a more effective and accurate drug development and diagnosis strategy. The team studied the gene transcription profile in blood samples from 158 pediatric lupus patients for up to four years, which allowed them to identify specific cell-related gene expression signatures — especially the gradual enrichment in neutrophils (immune cells related to inflammation), transcripts during progression to active nephritis and distinct signatures in response to specific treatments. This personalized immuno-monitoring revealed patient-specific correlations of disease activity and remission, which allows patient stratification into seven groups.

Researchers believe these findings further reveal the molecular heterogeneity of SLE and provide an explanation for the failure of many SLE clinical trials.

“The results included in this paper provide an explanation for why clinical trials fail in lupus, and opens the door for true personalized approaches to drug discovery and treatment in this disease,” Pascual said in a news release. “This is a landmark study that has the potential to dramatically improve treatment and quality of life for the hundreds of thousands of people suffering with lupus.”