Retinal inflammation plays a key role in the progression of age-related macular degeneration (AMD), a condition that leads to loss of central vision. The deposition of the acute phase pentraxin C-reactive protein (CRP) in the macula activates the complement system, thereby contributing to dysregulated inflammation. The complement protein factor H (FH) can bind CRP and down-regulate an inflammatory response. However, it is not known whether a truncated form of FH, called factor H-like protein 1 (FHL-1), which plays a significant regulatory role in the eye, also interacts with CRP. Here, we compare the binding properties of FHL-1 and FH to both CRP and the related protein pentraxin-3 (PTX3). We find that, unlike FH, FHL-1 can bind pro-inflammatory monomeric CRP (mCRP) as well as the circulating pentameric form. Furthermore, the four-amino acid C-terminal tail of FHL-1 (not present in FH) plays a role in mediating its binding to mCRP. PTX3 was found to be present in the macula of donor eyes and the AMD-associated Y402H polymorphism altered the binding of FHL-1 to PTX3. Our findings reveal that the binding characteristics of FHL-1 differ from those of FH, likely underpinning independent immune regulatory functions in the context of the human retina.,
Scientific Reports
Department of Hematology

Swinkels, M., Zhang, J.H. (Justine H.), Tilakaratna, V. (Viranga), Black, G. (Graeme), Perveen, R. (Rahat), McHarg, S. (Selina), … Clark, S.J. (Simon J.). (2018). C-reactive protein and pentraxin-3 binding of factor H-like protein 1 differs from complement factor H: Implications for retinal inflammation. Scientific Reports, 8(1). doi:10.1038/s41598-017-18395-7