Effector T-cells are expanded in systemic lupus erythematosus patients with high disease activity and damage indexes

Background and objectives T-cell activation may be one of the pathogenic mechanisms of systemic lupus erythematosus (SLE). After repeated antigenic stimulation, T-cells undergo different modifications, leading to the differentiation into effector memory T-cells (CCR7-CD45RA-) and terminally differentiated effector memory (TDEM) T-cells (CCR7-CD45RA+). Similarly, down-modulation of CD28 may lead to the expansion of the CD28- T-cells, a subpopulation with peculiar effector activities. The aim of this study was the characterization of T-cell phenotype in a cohort of patients with SLE according to disease activity and damage index. Materials and methods Phenotypic analysis of peripheral blood T lymphocytes of 51 SLE patients and 21 healthy controls was done by flow-cytometry. SLE disease activity was evaluated by SLE Disease Activity Index-2000 (SLEDAI-2K) and damage by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index (SDI). The variations between different groups were evaluated by Mann-Whitney test. Bonferroni correction was applied to adjust for multiple comparisons (p(adj)). Spearman rank test was used to evaluate the correlations between quantitative variables. Results CD4+ lymphopenia was found among SLE patients. Patients showed a trend for a higher percentage of TDEM among the CD4+ T-cell subpopulation in comparison with healthy controls (p=.04). SLE patients were divided into two groups according to disease activity: patients with SLEDAI-2K6 (n=13) had a higher percentage of circulating CD4+ T-cells with CD28- phenotype (p(adj)=.005) as well as those with an effector memory (p(adj)=.004) and TDEM (p(adj)=.002) phenotype and a trend of decrease of regulatory T-cells (TREGs) (p=.02), in comparison with patients with low disease activity (n=38). Patients with damage (SDI1) tended to show an expansion of TDEM among CD4+ T-cells as compared with patients with no damage (p=.01). In SLE patients an inverse correlation was found between the percentages of TREGs and those of TDEM (p<.01) or CD4+CD28- (p<.01) T-cells. Conclusions CD4+ T-cell subpopulations displaying phenotype characteristics of effector lymphocytes are proportionally expanded in patients with active SLE and a higher damage index. These findings may suggest a role of effector T-cells in the pathogenesis of the disease and in the mechanisms of damage in SLE.