A shift in the Th1/Th2 ratio accompanies the clinical remission of systemic lupus erythematosus in patients with end-stage renal disease

Background. Patients suffering from systemic lupus erythematosus (SLE) with renal involvement often show remission of systemic clinical activity after progression to end-stage renal disease (ESRD). SLE is characterized by predominantly humoral, T-helper (Th)(2)-mediated autoimmune responses. Since ESRD induces a state of immunodeficiency that affects the balance of Th cell subsets, we hypothesized that a Th-1 shift induced by ESRD leads to clinical remission of SLE. Methods. Using single-cell measurement of intracellular cytokines by flow cytometry after polyclonal stimulation with PMA/ionomycin, helper cell profiles were analysed in SLE patients with preserved renal function and in SLE patients with ESRD, from both isolated peripheral blood mononuclear cells (PBMC) and whole blood. Results. Using the whole-blood assay, patients with SLE and preserved renal function showed a predominance of Th-2 cells compared to healthy controls (patients, Th-1/Th-2, ratio 6.0 +/- 1.0 vs controls, 9.0 +/- 1.0; P<0.05). In contrast, SLE patients with ESRD have significantly more Th, cells (36.8 +/- 5.0%) than those without ESRD (23.4 +/- 3.6%; P<0.05). This results in an enhancement of the Th-1/Th-2 ratio to 12.1 +/- 2.6, which is not significantly different from healthy controls. These data were confirmed using a PBMC-based assay. Conclusions. SLE patients with preserved renal function show a bias in the differentiation of Th cells towards Th-2. Once ESRD occurs, the Th-1/Th-2 ratio normalizes. This may contribute to the remission of Th-2-mediated autoimmune diseases such as SLE.