Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement
The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.
Altered Balance Between the Effector and Regulatory T Cell Pathways in Systemic Lupus Erythematosus and Decreased Regulatory T Cell Levels in Active Lupus Nephritis
Mesquita1, Danilo, Cruvinel2, Wilson M., Araujo1, Julio A. P., Kallas3, Esper G., Andrade1, Luis Eduardo C.
Deficiency in CD4+CD25+ regulatory T cells (TREG) has been related to the pathogenesis of human and experimental autoimmune diseases. Controversy in published data on TREG frequency in systemic lupus erythematosus (SLE) is partially due to heterogeneity in phenotype TREG markers and in patient selection. We aimed to quantify TREG and effector T cells (TEFF) based on the CD25, CD127 and FoxP3 expression in active and inactive systemic lupus erythematosus (A-SLE & I-SLE).
Thirty-one patients with A-SLE (SLEDAI>6) and 32 patients with I-SLE (SLEDAI=0) fulfilling the ACR criteria were sequentially retrieved from the University Hospital outpatient clinic. Kidney involvement was defined according to the ACR criteria. Twenty-six HC were recruited among staff personnel. Peripheral blood mononuclear cells (PBMC) were analyzed by multicolor flow cytometry (FACSCANTO) and data analyzed using FlowJo software.
The frequency of CD25high cells was increased in A-SLE (5.2±5.7%) as compared to I-SLE (3.4±3.4) and HC (1.73±0.8%) (P=0.007). However, this did not represent an increase in TREG subset in A-SLE since the frequency of CD25+CD127low cells was equivalent in A-SLE (1.4±0.8), I-SLE (1.37±1.0) and HC (1.13±0.59) (P=0.42). In fact the percentage of FoxP3+ cells in the CD25high subset was decreased in A-SLE (24.6±16.4%) as compared to I-SLE (33.7±16) and HC (45±25.1%) (P<0.01). This was possibly due to an increased frequency of TEFF cells (CD25highCD127+FoxP3neg) in A-SLE (10.7±7.3%) as compared to I-SLE (8.5±6.5) and HC (6.1±1.8%) (P=0.02). Interestingly we observed a lower frequency of TREG cells (CD25+CD127lowFoxP3+) in renal A-SLE patients (0.8±0.4) as compared to non-renal A-SLE patients (2.19±1) (p<0.001).
The high degree of T cell activation in SLE hampers the use of CD25 as a marker for TREG since A-SLE samples present increased levels of CD25+ and CD25high effector T cells not related to TREG. There seems to be an altered balance between the effector and regulatory pathways in active SLE patients, especially in those with kidney involvement, and this imbalance may favor high effector T cell activity and thus contribute to the pathophysiology of this disease.
To cite this abstract, please use the following information:
Mesquita, Danilo, Cruvinel, Wilson M., Araujo, Julio A. P., Kallas, Esper G., Andrade, Luis Eduardo C.; Altered Balance Between the Effector and Regulatory T Cell Pathways in Systemic Lupus Erythematosus and Decreased Regulatory T Cell Levels in Active Lupus Nephritis [abstract]. Arthritis Rheum 2009;60 Suppl 10 :1748