Cell Membrane-bound TLR2 and TLR4: Potential Predictors of Active Systemic Lupus Erythematosus and Lupus Nephritis

Abstract

To the Editor: Innate immune receptors have been found to be involved in the pathogenesis of systemic lupus erythematosus (SLE)1. The binding of nucleic acids to the endosomal Toll-like receptors (TLR) 7 and TLR9 is considered as a triggering mechanism for the production of antinuclear antibodies2,3. Also, the cell membrane-bound TLR (mbTLR) might contribute to enhance immune cell responses in SLE. Besides detecting microorganisms, these receptors engage molecules exposed upon apoptosis, such as the DNA-binding high mobility group protein B1, which is thought to facilitate self-DNA antigenicity4. The contribution of the mbTLR TLR2 and TLR4 to loss of tolerance and development of nephritis has been consistently found in SLE models conducted in transgenic mice5,6,7. However, there is little information about the activation of mbTLR during SLE flares in humans. We have studied TLR2 and TLR4 protein levels in peripheral blood mononuclear cells from patients with SLE (n = 35) and healthy controls (n = 11) using flow cytometry. Patients were receiving stable medication at the time of the study, and had no signs of active infection. Whereas no global differences in the levels of the mbTLR were noted between the cohorts, the density of TLR4 was significantly increased in the B cells of patients with active (n = 20) … Address correspondence to Dr. O. Sanchez-Pernaute, Division of Rheumatology, Jimenez Diaz Foundation Health Research Institute and University Hospital, Avda. Reyes Catolicos 2, 28040 Madrid, Spain. E-mail: osanchez{at}fjd.es