Functional Precision Medicine in Rheumatoid Arthritis Save

Novels research from the Medical University of Vienna demonstrates the plausible utility of functional precision medicine (FPM) using immunophenotyping of blood cells (PBMCs) with rheumatoid arthritis (RA), to help guide treatment selection.

 

A high content, high throughput microscopy-based phenotyping of patients PBMCs was used to study cell types, cell morphology and intercellular interactions in RA (n = 65) and healthy controls (HC, n = 33). Cell samples were exposed to a set of RA-specific small molecules, biologicals and reference stimuli for 24 h to assess ex vivo drug effects. These ex vivo PBMC phenotypic results were integrated with patients’ current medication and disease activity.

 

The results confirmed the performance of high content microscopy to detect and quantify known immunologic phenotypes. The promise being that PBMC phenotypes may be susceptible to specific to drug treatment and RA disease activity. Secondarily, they examined the effects of ex vivo drug treatment (DMARDs and biologics) and found current drugs to have morphologic effects on RA and HC’s PBMCs. The arrayed ex vivo drug perturbation enabled the systematic characterization of drug effects, clustering by mode of action and uncovered morphologic alterations associated with biologic disease-modifying anti-rheumatic drug (DMARD) treatment. Individual in vivo treatment regimens translated into altered immune cell abundances in patients with a comedication of conventional synthetic DMARDs when compared to HCs. Global integration of PBMC characteristics led to clustering of patients according to disease activity and correlation with clinical data.

 

This is a developing screening tool demonstrating technical proof-of-concept as a means to better characterized RA patients and test its utility in choosign future therapies; a functional precision medicine approach.