Lymphocyte phenotype and its application to precision medicine in systemic autoimmune diseases✰.

Systemic lupus erythematosus (SLE) is a representative autoimmune disease characterized by multiple organ manifestations but is molecularly and genetically heterogeneous which makes difficult to manage every case based on one kinetic molecular theory. We, therefore, have tried to obtain a broader perspective on the molecular heterogeneity in SLE by immunophenotyping and found that patients with active SLE can be divided into 3 subgroups based on T cell heterogeneity. Although immunophenotypic features were different even among patients with similar clinical features, patients resistant to treatment were most frequently seen in the follicular helper T cell-dominant group. Because belimumab is only approved targeted therapy for SLE, the concept was encompassed with psoriatic arthritis (PsA) for which multiple biologics are approved. The obtained results suggest the potential for precision medicine via the strategic selection of different biologics based on the phenotypic differences in peripheral helper T cells in individual patients with PsA. Thus, subgrouping heterogeneous diseases could provide good bases for precision medicine, which would encourage treatment strategies of diseases with high clinical and molecular heterogeneity such as SLE.