CD4+CD45RA-FOXP3low Regulatory T Cells as Potential Biomarkers of Disease Activity in Systemic Lupus Erythematosus Brazilian Patients

CD4+CD45RA-FOXP3low 调节性 T 细胞作为巴西系统性红斑狼疮患者疾病活动的潜在生物标志物

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作者:Helena L Silva-Neta, Maria C A Brelaz-de-Castro, Mardonny B O Chagas, Henrique A Mariz, Rodrigo G de Arruda, Viviane F de Vasconcelos, Michelly C Pereira, Audrey Romano, Ivan R Pitta, Claudia D L Marques, Angela L B P Duarte, Moacyr J B M Rêgo, Maira G R Pitta

Abstract

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+FOXP3highCD45RA-) (p=0.01) subtype was inversely correlated with disease activity while Foxp3+nontreg (CD4+FOXP3lowCD45RA-) (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.

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