Genetic polymorphisms of endosomal TLR in systemic lupus erythematosus

Toll-like receptors (TLR)-3, TLR7, TLR8 and TLR9 are located in the endosomal membrane and they are specialized in the recognition of different types of microbe-derived nucleic acids. However, endogenous nucleic acids can also activate these TLR triggering autoimmunity. Currently, these endosomal TLRs have been demonstrated to be involved in the development and progression of autoimmune diseases such as systemic lupus erythematosus (SLE).
As many other autoimmune diseases, SLE is a chronic inflammatory disease that can affect any and every organ system of the body and courses with remission and flares. It is characterized by a polyclonal B cell activation leading to an overproduction of pathogenic autoantibodies directed against intracellular antigens, primarily nucleic acids and nucleic acid-associated proteins, generating immune complexes which may cause tissue damage by deposition.
Although the aetiology of SLE remains unknown, environmental and genetic factors, including both MHC and non-MHC genes have been proposed. Several genetic variations of TLR modify expression and/or costimulatory capacity of nucleic acid-sensing TLRs which could lead to differences in B cell and dendritic cell response to autoantigens and DNA- or RNA-immune complexes. Therefore, such genetic variation may have an effect on susceptibility to SLE and disease progression.
The aim of this study is to evaluate the involvement of single nucleotide polymorphisms (SNPs) of endosomal TLRs in the susceptibility and clinical autocome of patients with SLE.