Precision Medicine Study Examines Blood-Based Immunophenotyping in Patients with RA

“Our findings underscore the often-overlooked diversity among RA patients in routine clinical practice. We have demonstrated that stratifying patients has proven to be meaningful in both basic research and clinical practice,” Dr. Kubo says.

Research & Clinical Implications

“In academia, our results emphasize the significance of translational research, specifically clinical immunology, in addressing discrepancies between human and mouse studies,” Dr. Kubo says. “For clinical medicine, we have highlighted our expectations for the advancement of future precision medicine. Our findings also indicate that various critical cell subsets, such as CD4 TEMRA, contribute to the pathogenesis. By exploring the differentiation and regulation of these cell subsets, we possess the potential to identify novel target molecules for RA.

“In patients with RA, who exhibit considerable diversity, the critical question is determining the appropriate medication for each case,” concludes Dr. Kubo. “This study concentrated on assessing the heterogeneity of RA and successfully identified immune cell fractions that are unmeasurable in routine clinical settings, thus evaluating this diversity. Moreover, we demonstrated that this variability is instrumental in selecting targeted molecular therapies, marking an advancement towards the realization of precision medicine in the future.”

Commenting on the findings, Christian Lood, PhD, an associate professor in the Division of Rheumatology at the University of Washington, Seattle, notes that the study highlights the need for the “incorporation of blood-based markers in making treatment decisions on an individual basis, recognizing that not all treatments will be efficient for all individuals. This assumption is supported by several similar findings, including a recent study by our group demonstrating the clinical utility of blood-based immunophenotyping in guiding treatment decisions.”

Incorporating Blood-Based Markers

Dr. Lood

In a 2024 study, Dr. Lood and colleagues assessed whether baricitinib, a JAK1/JAK2 inhibitor, reduced neutrophil activation and whether a neutrophil activation score predicted treatment response.²

They used an enzyme-linked immunosorbent assay to measure neutrophil activation markers, calprotectin and neutrophil extracellular traps in plasma. The markers of neutrophil activation stood elevated in the 271 patients with RA compared with the 39 healthy controls. Baricitinib reduced calprotectin levels at 12 and 24 weeks, especially in patients responding to treatment. Elevated baseline levels of calprotectin and neutrophil extracellular traps could predict treatment response to baricitinib, but C-reactive protein levels could not distinguish responders from non-responders.”

“A deepened understanding of the heterogeneity of the disease and clinical utility of blood-based markers may change the way we view and perform clinical trials, focusing on patients with distinct molecular and/or cellular profiles anticipated to be targeted by the treatment rather than being all inclusive,” Dr. Lood says.