Different Immunologic Profiles are Associated with Distinct Clinical Phenotypes in Longitudinally Followed Systemic Lupus Erythematosus Patients

Objective To determine the immunologic profile associated with flares of systemic lupus erythematosus (SLE) and to investigate the clinical significance of any differences observed between patients during and following flare. Methods Multi‐parameter flow cytometry was used to examine 47 immune populations within the peripheral blood of 16 healthy controls, 25 clinically quiescent SLE patients and 46 SLE patients experiencing a flare, at baseline and at 6‐ and 12‐month follow‐up visits. Unsupervised clustering was used to identify subjects with similar immune profiles and to track changes over time. Parametric or non‐parametric statistics were used, where appropriate, to assess the association of cellular phenotypes with clinical and laboratory parameters. Results Five clusters of subjects were identified that variably contained active and quiescent SLE patients and that had distinct clinical phenotypes. Patients characterized by increased T peripheral helper, activated B, and age‐associated B cells were the most likely to be flaring at baseline, as well as the most likely to remain active or flare over the subsequent year if they acquired or retained this phenotype at follow‐up. In contrast, patients who had increased T helper cells in the absence of B cell changes, or who had increased T h 1 cells and innate immune populations, mostly became quiescent on follow‐up. A significant proportion of SLE patients had depletion of many immune populations at flare and only showed increases in these populations post‐flare. Conclusion Cellular phenotyping of SLE patients reveals several distinct immunologic profiles that may help to stratify patients with regard to prognosis and treatment. image