Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.
The Monitoring of FoxP3 Expressing CD4 T Cell Subsets May Be Helpful for the Prediction of Systemic Lupus Erythematosus Flares.
Miyara1, Makoto, Mathian1, Alexis, Haroche1, Julien, Arnaud2, Laurent, Chader1, Driss, Musset1, Lucile, Gorochov1, Guy
Based on the functional delineation of FoxP3 expressing CD4+ T cell subsets that we defined recently, we have shown that perturbation in Treg cell homeostasis may participate in the immunopathogenic mechanisms that lead to SLE flares. Whether modifications in FoxP3 expressing CD4+ T cell subsets are observed in patients before they develop SLE flares has not been determinde yet.
Patients with inactive SLE (SLEDAI <6, n=45) were included for a 6 month follow-up. Clinical and biological evaluation of SLE activity and analysis of the proportions of FoxP3 expressing subsets were performed every 2 months. Normal values of each FoxP3 expressing CD4+ T cell subsets were defined in a cohort of 50 healthy donors as follows: naïve Treg cells (nTreg) defined as CD4+FoxP3lowCD45RA+ cells: 2.4% (14.5%), effector Treg cells (eTreg) as CD4+FoxP3highCD45RA- cells: 1.55% (13%) and FoxP3 non Treg cells (FoxP3+nonTreg) defined as CD4+FoxP3lowCD45RA-: 3.05% (1.35.8%).
20 patients (44.4 %) had normal proportions of nTreg, eTreg and FoxP3+nonTregs at inclusion. The most frequent anomaly was an isolated increase in the proportion of FoxP3+nonTregs (n=11, 24.4%). Other anomalies were: decrease in eTreg (n=2, 4.4%), decrease in nTreg cells (n=2, 4.4%), increase in nTreg cells (n=2, 4.4%), increases in both FoxP3+nonTreg and nTreg (n=4, 8.8%), combination of increase in FoxP3+nonTreg and decrease in nTreg, (n=3, 6.6%), decrease in both nTreg and in eTreg (n=1, 2.2%). Increase in FoxP3+nonTreg was thus observed in 18 patients (40%), decrease in nTreg in 6 (13%), increase in nTreg in 6 (13%) and decrease in eTreg cells in 3 patients (6.7 %).
Only one patient among the patient that did not display anomalies in any FoxP3 expressing subset at inclusion developed a mild flare (arthritis, 5%) while, among those with anomalies, 5 patients developed SLE flares including 2 nephritis (20%). The most prevalent anomaly observed before flares was an increase in FoxP3+nonTreg (n=4) while an increase in nTreg was observed in 3 patients, a decrease in nTreg in 2 and a decrease in eTreg cells in 3.
Among the 25 patients that had anomalies at inclusion, only 4 of them returned to normal proportions. None of them developped SLE flare. Among the 21 patients that kept anomalies, 5 of them developed SLE flares (25%). Most patients without anomalies at inclusion (n=20) developed a new anomaly 6 months later (n=12, 60%) that was mainly an increase in FoxP3+nonTreg (n=8, 75%). Of note, the last patient that developed a mild SLE flare belonged to this group. Thus, 8 patients kept normal proportions of FoxP3 expressing subsets and did not develop SLE flare.
Although phenotypically similar, inactive SLE patients have different patterns in the proportions of FoxP3 expressing CD4+ T cell subsets. Most patients that developed SLE flares during the 6 month follow-up had anomalies in FoxP3 expressing CD4+ T cells subset before flares while those who maintained the absence of anomaly did not develop flares. The monitoring of FoxP3+ CD4+ T cell subsets may be a novel efficient parameter for the prediction of SLE flares in SLE outpatients.
The study was supported by ARTHRITIS Fondation Courtin
To cite this abstract, please use the following information:
Miyara, Makoto, Mathian, Alexis, Haroche, Julien, Arnaud, Laurent, Chader, Driss, Musset, Lucile, et al; The Monitoring of FoxP3 Expressing CD4 T Cell Subsets May Be Helpful for the Prediction of Systemic Lupus Erythematosus Flares. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :658