CD4(+)CD45RA(−)FOXP3(low) Regulatory T Cells as Potential Biomarkers of Disease Activity in Systemic Lupus Erythematosus Brazilian Patients

Heren, we analyzed Treg cells as potential biomarkers of disease activity in systemic lupus erythematosus (SLE) patients. Peripheral blood mononuclear cells from 30 SLE patients (15 active: SLEDAI > 6/15 SLE remission: SLEDAI< 6) and 15 healthy volunteers were purified. Treg immunophenotyping was performed using CD4, CD25, CD45, CD127, and FOXP3 markers. CD4(+)FOXP3(+) Treg activation state was investigated based on CD45RA and FOXP3 expression. To increase the accuracy of our findings, a multivariate linear regression was performed. We showed a significant increase in the frequency of CD4(+)FOXP3(+) Treg cells in SLE patients. However, unlike all other Treg cells phenotypes analyzed, only eTreg (CD4(+)FOXP3(high)CD45RA(−)) (p=0.01) subtype was inversely correlated with disease activity while Foxp3(+)nontreg (CD4(+)FOXP3(low)CD45RA(−)) (p=0.003) exerted a direct influence in the outcome of the disease. Foxp3(+)nontreg cells were the most consistent SLE active indicator, confirmed by multiple linear regression analyses. In summary, our results demonstrate Foxp3(+)nontreg cells as new biomarkers in the search of an effective therapeutic strategy in SLE.