Background/Purpose: Cognitive impairment (CI) in systemic lupus erythematosus (SLE) may be associated with different T cell subpopulations distribution and chronic pro-inflammatory state in which immunosenescence could be involved. This study investigates the distribution of T cell subpopulations and immunosenescent markers in SLE patients with CI.

Methods: We included women aged 18-50 years, classified with SLE according to the EULAR/ACR 2019 criteria. Women with other autoimmune diseases except antiphospholipid syndrome or Sjögren’s syndrome, administration of any biologic drug < 6 months prior to study entry, clinical SLEDAI-2K >0, SDI ≥1, current prednisone >7.5 mg/day, education level ≤6 years, pregnancy or premature ovarian failure, active infection, malignant disease, history of other neuropsychiatric manifestations, other chronic comorbidities or major depressive disorder were excluded. We also include healthy women (HC) paired for age ±5 years. We applied a neurocognitive battery, assessing eight cognitive domains: concentration, verbal memory, visuospatial memory, language, processing speed, motor speed, problem solving and executive function. CI was defined when a subject had scores ≥2 standard deviation below the mean of the normative data in at least one cognitive domain. According to the neurocognitive assessment patients were classified as: SLE with CI, SLE without CI and HC. The lymphocyte subpopulation profile for each patient was determined by flow cytometry. A CD4+/CD8+ ratio of < 1 (inverted ratio) was considered a marker of immunosenescence. The relative expression of the p16INK4a gene in CD3+ T lymphocytes was considered another marker of immunosenescence and was assessed through CD3+ cell purification from peripheral blood, RNA extraction, qPCR, and evaluation of relative expression (ddCT) normalized to the housekeeping gene GAPDH. Demographic and clinical data were also recorded.

Results: Fifteen patients in each group were included. The median age of patients studied was similar. SLE patients with CI had lower educational level than the SLE without CI and HC, and longer disease duration compared to SLE patients without CI. Disease activity and accrual damage was similar between the SLE groups (Table 1). In SLE patients with CI, the most frequently impaired cognitive domain was motor speed (73.3%), followed by visuospatial memory (33.3%), processing speed (13.3%), verbal memory (6.6%), language (6.6%), and problem solving (6.6%) (Figure 1). SLE patients with CI had significant lower levels of naive CD4+T cells and higher levels of CD8+ T cells compared to the other groups. The proportion of inverted CD4+/CD8+ ratio and relative expression of p16INK4a were greater in SLE with CI compared to SLE without CI and HC groups (53.3% vs. 20.0% vs. 0%, p=0.003 and 1.6 [1.0-2.3] ddCT vs. 0.8 [0.4-2.2] ddCT vs. 0.6 [0.5-1.0] ddCT, p=0.005, respectively) (Table 1, Figure 2).

Conclusion: In SLE with CI there were lower levels of naïve CD4+ T-cells, higher levels of CD8+ T cells and greater presence of immunosenescence markers compared to SLE without CI and HC. The study suggests the possibility that immunosenescence may play a role in CI in SLE.

Data are expressed as proportions (percentages) or medians (interquartile ranges). Statistical analysis: Chi-square or Fisher’s exact tests were used for nominal variables, the Kruskal-Wallis test was used for numerical variables. CM: central memory, EM: effector memory, TEMRA: effector memory T cells re-expressing CD45RA. *Statistically significant.

Figure 1. Impaired cognitive domains in SLE patients with CI.

Data are expressed as percentages.

Figure 2. Statistical significant differences in subpopulations and senescent markers in T cells of studied patients.

HC: healthy control, SLE: systemic lupus erythematosus, CI: cognitive impairment.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/evaluation-of-t-cell-subpopulations-cd4-cd8-ratio-and-p16ink4a-in-patients-with-systemic-lupus-erythematosus-and-cognitive-impairment/