Systemic lupus erythematosus (SLE) is a complex, multifactorial autoimmune disease that predominantly affects women of childbearing age. It is characterized by the production of autoantibodies directed against nuclear antigens, whose deposits trigger inflammation that may affect various organs, particularly the joints, skin, central nervous system, and kidneys. Lupus nephritis, observed in approximately 30 to 50% of patients, is one of the most severe manifestations of the disease: between 5 and 20% of affected patients progress to end-stage renal failure within ten years of diagnosis, requiring renal replacement therapy. It has long been known that lupus activity tends to decline after the initiation of maintenance dialysis. However, the immunological mechanisms underlying this decline remain poorly understood, and the decision to continue or discontinue maintenance therapy remains challenging: an inappropriate choice exposes patients either to disease flares or to an increased risk of infection.
To clarify these issues, the authors undertook a detailed immunological characterization of lupus patients on dialysis, whether their disease was active or inactive. Using multiparameter flow cytometry, extensive immunophenotyping was performed on blood samples from 47 hemodialyzed lupus patients, 10 non-dialyzed patients with active lupus nephritis, 6 non-dialyzed patients with a history of lupus nephritis currently in remission, and 20 healthy volunteers serving as controls. The hemodialysis group comprised 16 patients with inactive disease, 22 with sustained low activity (non-renal SELENA-SLEDAI score ≤ 4), and 9 patients with high activity. A discriminant factor analysis based on twelve cellular variables validated the association between immune signatures and lupus activity.
This work shows that dialysis patients with high activity display, like active non-dialyzed patients, a characteristic combination: an increase in circulating "atypical naïve" B lymphocytes (CD19hi CD27–), plasmablasts, and CD16+ inflammatory monocytes, associated with basopenia. The analysis also groups low-activity patients (≤ 4) together with inactive patients and those in remission; some of them would in fact correspond to serologically active but clinically quiescent lupus, consistent with inactive disease.
On this basis, the authors propose a simple immunophenotypic approach, based on the flow cytometric quantification of four readily identifiable leukocyte populations, as an objective biomarker of lupus activity in hemodialyzed patients, particularly when clinical manifestations are not specific to the disease. They emphasize that this strategy will need to be confirmed in independent cohorts before its clinical benefit can be validated for both dialyzed and non-dialyzed patients.