Flow cytometry and systemic lupus erythematosus: how cells tell the story of the disease

Systemic lupus erythematosus (SLE) is a complex, multisystemic, and highly heterogeneous autoimmune disease. Its diagnosis and clinical monitoring have traditionally been challenging due to the variability of symptoms, fluctuating activity, and the absence of single, universal biomarkers—challenges that flow cytometry is increasingly helping to overcome.

In this context, flow cytometry emerges as a fundamental tool to unravel the cellular behaviour of the immune system in real time, allowing not only to characterise specific immune subpopulations, but also to monitor the patient’s evolution and response to treatment.

What is the benefit of flow cytometry in lupus?

Flow cytometry allows the analysis of individual immune cells based on their physical characteristics (such as size and granularity) and molecular characteristics (presence of surface or intracellular proteins). This is especially relevant in SLE, where profound alterations occur in multiple components of the immune system.

1. Key applications in SLE: T and B lymphocyte phenotyping
   

• Regulatory T lymphocytes (Tregs): their decrease is associated with loss of immune tolerance.
• Activated (CD69*, HLA_DR+) and exhausted (PD-1*) T lymphocytes: reflect chronic activation or dysfunction.
• Memory and activated B lymphocytes (CD19⁺CD27⁺CD38⁺): frequently expanded in active outbreaks, contribute to the production of autoantibodies.

2. Plasmacytoid dendritic cells (pDCs)

These cells are a major source of type I interferon, key in the pathophysiology of SLE. Their altered frequency and activation can be measured by cytometry as an indicator of inflammatory activity.

3. NK cells and monocytes

• Decreased cytotoxic NK cells (CD56dimCD16⁺).
• Phenotypic changes in CD14⁺CD16⁺ monocytes, related to endothelial damage and renal involvement.

Monitoring of disease activity

One of the clinical challenges in SLE is to differentiate between real immune activity and chronic damage or non-inflammatory symptoms. Flow cytometry allows:

• Quantify cellular biomarkers that correlate with activity indices (such as SLEDAI).
• Identify early therapeutic responses to immunosuppressive or biologic treatments.
• Detect imminent relapses by monitoring autoreactive B lymphocytes or interferon signatures.

In recent studies, combinations of activated B subpopulations + PD-1 expression in T cells have shown predictive capacity of imminent relapses.

Beyond diagnosis: impact on clinical research

Flow cytometry is not only useful in clinical practice. It is also essential in:

• Clinical trials: to establish immunological endpoints and select patient subgroups.
• Precision medicine: to define immunological profiles and tailor personalized treatments.
• Discovery of new biomarkers: using multiparametric panels that evaluate up to 18-20 markers per cell.

Conclusion: understanding lupus at the cellular level

Lupus does not only manifest itself in flares or autoantibody tests. Its true dynamics occur at the cellular level, in an overactive, dysfunctional and poorly regulated immune system.

At Immunostep we work to put this technology at the service of researchers and clinicians fighting autoimmune diseases like lupus Because every cell counts. And every piece of information, properly interpreted, can change the course of a disease.