Peripheral Apoptotic Lymphocytes May Predict Disease Activity in Juvenile SLE

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Peripheral apoptotic lymphocytes may contribute to the diagnosis of juvenile-onset systemic lupus erythematosus (jSLE) and could be used to predict disease activity in this patient population, according to research published in Pediatric Rheumatology.¹

“The defective clearance of apoptotic bodies in jSLE potentially leads to the persistence of autoreactive lymphocytes and the perpetuation of the autoimmune response,” wrote Eman Eissa, PhD, associated with the Department of Immunogenetics, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt, and colleagues. “These factors contribute to the disturbance in lymphocyte apoptosis and show potential as key determinants in the clinical course and severity of jSLE.”

Lymphocyte apoptosis plays a fundamental role in maintaining immune homeostasis by coordinating the elimination of autoreactive and senescent lymphocytes and the clearance of apoptotic bodies. However, in patients with jSLE, there is a disruption in the balance between apoptosis and cell survival mechanisms, which can lead to the persistence of autoreactive lymphocytes and an autoimmune response.²

To evaluate the role of peripheral blood (PB) lymphocyte apoptosis in the prognosis of jSLE as well as a predictor for disease activity, investigators recruited 100 patients with jSLE and 50 healthy controls within a Rheumatology and Rehabilitation outpatient clinic, Kasr Al Ainy Hospital, Cairo University, between April and December 2022. Eligible patients met the Systemic Lupus Collaborating Clinics (SLICC) classification criteria for SLE. The proportion of lymphocyte apoptosis in PB among the entire cohort was analyzed using flow cytometry. ELISA determined the plasma levels of pro-inflammatory cytokines.

Within the patient cohort, 96% (n = 96) were female, the mean age at baseline was 25 years, median disease duration was 140 months, and 22% (n = 22) reported a family history of either SLE or other autoimmune conditions.

Results revealed the percentage of lymphocyte apoptosis in PB was significantly higher in patients with jSLE when compared with healthy controls (P <.001). Additionally, these percentages were significantly positively associated with disease activity in patients, according to the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K; P <.001). Patients with active jSLE had significantly higher percentages of PB lymphocyte apoptosis when compared with those with inactive disease (P = .002).

Plasa cytokine levels, such as interleukin-17 (IL-17), tumor necrosis factor-alpha (TNF-α), and interferon gamma (INF-γ) were significantly elevated in the patient population when compared with healthy controls (P <.001).

Weak significant positive correlations were observed between percentages of PB lymphocyte apoptosis and each of the IL-17 and IFN-γ plasma levels in patients with jSLE. Further, PB lymphocyte apoptosis percentages among patients were higher in the presence of certain laboratory and clinical features than those in their absence.

Investigators noted the small sample size as a limitation of the study. Additionally, the drugs patients were prescribed to patients may have affected the percentages of lymphocyte apoptosis. Despite this, the findings are an important facet of exploring the role of lymphocyte apoptosis and disease activity in this patient population.

“Further studies are needed to elucidate the sequence of events revealed in the results regarding the interplay between apoptotic lymphocytes and inflammatory cytokines,” investigators concluded. “These studies should determine whether apoptotic lymphocytes are a consequence of systemic inflammation or if it acts as the driving force behind such events, possibly influenced by other serum factors. Identifying the trigger for these events should be the focus of future research aimed at exploring potential therapeutic solutions.”

References

1. ^{Eissa, E., Kandil, R., Dorgham, D. et al. Lymphocyte apoptosis and its association with the inflammatory markers and disease severity in juvenile-onset systemic lupus erythematosus patients. Pediatr Rheumatol 22, 20 (2024). https://doi.org/10.1186/s12969-024-00953-9}
2. ^{Hedrich CM, Smith EMD, Beresford MW. Juvenile-onset systemic lupus erythematosus (jSLE) - Pathophysiological concepts and treatment options. Best Pract Res Clin Rheumatol. 2017;31(4):488–504.}