TLR-9, but not TLR-2, TLR-3 and TLR-4, is upregulated on peripheral blood mononuclear cells of patients with active systemic lupus erythematosus

Background

Innate immune responses may augment adaptive immune responses via the adjuvant effect of endogenous apoptotic cell death derived nucleic acids that activate Toll-like receptors (TLRs). In animal models of lupus, activation of TLR-9 accelerates renal disease. We studied the expression of TLR-2, TLR-3, TLR-4 and TLR-9 in the peripheral blood mononuclear cells from patients with systemic lupus erythematosus (SLE).

Materials and methods

Peripheral blood mononuclear cells from 18 SLE patients, four patients with other rheumatic disorders and three normal controls were studied for the expression of TLRs by FACS analysis. TLR-2, TLR-3, TLR-4 and TLR-9 expressions was studied in total lymphocytes, CD19⁺ and CD14⁺ cells. Disease activity was assessed by the SLEDAI. Patients were divided into those with active/severe disease and those with inactive/mild disease.

Results

Eight out of 18 patients had active disease with mean SLEDAI score 12.3 (± 9.9) while 10 had inactive disease with mean SLEDAI score 2.8 (± 0.9). Lymphocyte expression of TLR-9 (mean value and standard deviation) was higher among patients with active/severe disease in comparison with patients with inactive lupus (64 ± 18%, n = 8 versus 19 ± 14%, P < 0.003) (Table 1).

Table 1 Table 1

There were no differences between patients and healthy controls regarding the expression of TLR-2, TLR-3 and TLR-4. The expression of TLR-9 on various B-cell subpopulations of patients with SLE is currently under investigation.

Conclusions

TLR-9, but not TLR-2, TLR-3 and TLR-4, is upregulated in peripheral lymphocytes from SLE patients with active/severe disease compared with patients with inactive/mild disease. There is also a trend for increased expression of TLR-9 at least on CD19⁺ and CD14⁺ cells. Experiments in progress examine the response of these cells to TLR stimulation.