Background Low numbers of T regulatory cells (Tregs) in active systemic lupus erythematosus (SLE) are believed to reflect the breakdown of immune tolerance in disease pathogenesis. However, it is not clear if these cells may be utilized as a biomarker in assessing disease activity.
Objectives of the present study was the prospective evaluation of Tregs as possible biomarkers in assessing SLE activity.
Methods Tregs (phenotype CD4+CD25highFOXP3+) were assessed by flow cytometry in 285 separate blood samples from 100 white Caucasian SLE patients and 20 healthy controls. Patients were divided, according to disease activity (as measured by Systemic Lupus Erythematosus Disease Activity Index, SLEDAI) into groups A (n=39, samples=94, SLEDAI=0), B (n=33, samples=92, SLEDAI=1-5), C (n=10, samples=53, SLEDAI=6-10) and D (n=18, samples=46, SLEDAI>10). Longitudinal measurements were performed in 131 cases (37 relapses, 44 remissions and 50 cases without alteration in disease activity). Statistics were performed by Student’s t-test or one-way ANOVA, post hoc analysis with Bonferroni multiple comparisons test and correlations with Pearson co-efficient; while p<0.05 was considered significant.
Results Tregs were found significantly lower in severely active disease (group D), compared to healthy controls, inactive disease, mild and moderate disease activity (0.57±0.16% vs. 1.49±0.19%, 1.19±0.34% and 1.05±0.36%, 0.72±0.21%, p<0.05, respectively). There was a strongly inverse correlation between Tregs and SLEDAI (r=-0.644, p<0.001). Alterations in disease activity were characterized by inverse alterations in Tregs: relapse (from 1.23±0.44% to 0.64±0.19%, p<0.001, mean change 0.59±0.41%), remission (from 0.65±0.27% to 1.17±0.30%, p<0.001, mean change 0.52±0.35%). In cases with unaltered disease activity, Tregs numbers remained stable (from 0.98±0.35% to 1.03±0.34%, p=0.245). Tregs were practically halved during relapse (mean reduction 42.6±22.2%), and doubled during remission (mean increment 113±120.9%). Mean change of Tregs in cases with unaltered activity was significantly lower (7.3±20.6%, p<0.001). A clinically significant change in SLEDAI (sum of cases with relapse and remission, n=81) was followed by a significant (>20%) inverse change in Tregs in 71/81 cases (sensitivity 87.7%). In the 50 cases of unchanged SLEDAI, Tregs were significantly changed (>20%) in 13 cases (specificity 74%). Positive predictive value (PPV) was 84.5% and negative predictive value (NPV) was 78.7%.
Conclusions CD4+CD25highFOXP3+ T regulatory cells displayed a strongly inverse correlation to disease activity, while their alterations reflected the changes in SLEDAI with high sensitivity. These cells may be a promising biomarker for the assessment of disease activity in SLE by longitudinal measurements.
Disclosure of Interest: None Declared