Researchers discover seven major molecular subgroups of lupus patients

Researchers including Jacques Banchereau of The Jackson Laboratory have uncovered distinct molecular subgroups of patients with systemic lupus erythematosus (SLE), providing an explanation for why clinical trials might fail and opening opportunities for new and more targeted treatments of the disease. Their findings are published in the journal Cell.

SLE is an incurable, systemic autoimmune disease predominantly affecting young women. A major hurdle in lupus therapy development is the lack of knowledge about molecular mechanisms driving disease activation in individual patients.

In the past 50 years the FDA has approved only one new treatment (belimumab). While several other treatments improved disease in preclinical models and small phase I and phase 2 clinical trials, larger phase III trials have proved unsuccessful.

The research team, led by Virginia Pascual of Baylor Institute for Immunology Research, had previously conducted blood transcriptomic studies to discover successful targets to treat children with arthritis. To gain insight into the molecular heterogeneity of SLE, they profiled the blood transcriptome of a longitudinal cohort of 158 pediatric patients using a personalized immunomonitoring approach.

The researchers uncovered individual correlates of disease activity that enabled them to stratify the patients into seven distinct molecular subgroups. Their approach offers a new way to improve trial design and implementation of tailored therapies in lupus and other genetically and clinically complex autoimmune diseases.

Banchereau et al.: Personalized Immunomonitoring Uncovers Molecular Networks that Stratify Lupus Patients. Cell,