Although the functional consequences of genetic variability in the TLR3 locus have not been defined in detail it is tempting to speculate that polymorphisms in the TLR3 gene may not only have an impact on the risk of developing sero-negative RA but may also play a role as disease activity modifier in sero-negative RA as reflected by the association with DAS28 and swollen joint count. The gene discussed is TLR3; the disease is rheumatoid arthritis.