Abstract 548: TLT-1 as a Possible Modulator of Systemic Lupus Erythematosus

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by immune system hyperactivity and autoantibody production that can affect almost any organ system. TREM like transcript-1 (TLT-1) is a membrane receptor found in platelets α-granules with activating properties. We have demonstrated that activated platelets release a soluble isoform of TLT-1 (sTLT-1) which is not found in the plasma of healthy individuals. Moreover, evaluation of patients suffering from inflammatory diseases, such as sepsis, reveals a significant increase of plasma sTLT-1 levels. It is not known if TLT-1 plays a role in auto immune diseases such as Lupus. In the present study we evaluate the potential that TLT-1 may play a role in the etiology of SLE. We assessed the plasma of 46 SLE patients and compared to 28 healthy controls by ELISA. Our results showed that SLE patients had a significant decrease in plasma sTLT-1 levels compared to healthy controls (9.0 [7.2] vs. 18.6 [22.3] ng/ml, p=0.008). A negative correlation was observed between TLT-1 levels and LupusPRO [lupus symptoms (r = -0.388, p = 0.055). Based on this data; we hypothesize that SLE patients produce autoantibodies against TLT-1 in serum which might correlate with clinical aspects of the disease . To address this question; TLT-1 antibodies levels in serum were measured by ELISA. Our data suggests that a sub-population of SLE patients have TLT-1 autoantibodies. This data was further confirmed by confocal microscopy. Using human embryonal kidney cells (HEKt) stably transfected with TLT-1, we evaluated the serum of SLE patients for the presence of TLT-1 autoantibodies using immunofluorescence. Our data confirms that a sub-population of SLE patients with active disease is expressing antibodies against TLT-1. These findings suggest a possible role for TLT-1 during the pathogenesis of SLE and targets new treatment possibilities for lupus patients.