Toll-like receptors revisited; a possible role for TLR1 in lupus nephritis

Several studies in systemic lupus erythematosus (SLE) have shown a possible role of endosomal toll-like receptors (TLRs) in lupus nephritis (LN), but the role of those interacting with ligands in the plasma membrane remains unclear.1 Herein, we revisit the genetic contribution of TLRs in SLE inspired by a patient with LN who carries a rare TLR1 variant. We analysed coding and regulatory regions of the TLR1–10 genes in 855 patients with SLE (online supplemental data 1). Six variants (rs142003616, rs76600635, rs72493538, rs41305843, rs113706342, rs41311400) within TLR1, one (rs10006364) within TLR2, one (rs79088436) within TLR5 and two (rs55695972, rs117985012) within TLR6 were significantly enriched in LN but only rs142003616 (TLR1) remained significant after Bonferroni correction (p<0.039, online supplemental table 1). To assess its biological significance, we employed in-silico functional annotation. The calculated deleteriousness score, CADD PHRED, for rs142003616 (5.56) points at the variant’s potential functional importance. The rare risk allele is predicted to create a strong binding site for the core binding factor (CBF).2 CBF, also known as runt-related transcription factors (RUNX), are also associated with SLE, psoriasis and rheumatoid arthritis.3 To evaluate rs142003616 functional potential, we lastly …