Identification of homing peptides specific for human synovium by in vivo phage display selection

Background

The microvascular endothelium (MVE) plays a major role in the pathogenesis of rheumatoid arthritis (RA). There is evidence to suggest that tissue-specific MVE determinants are involved in selective recruitment of pathogenic immune cells to sites of inflammation.

Objective

The aim of this work was to target the synovial MVE in tissue grafts transplanted into mice with SCID (severe combined immunodeficiency), using phage display.

Methods

Human synovium and skin were transplanted into SCID mice. A disulfide-constrained seven-amino-acid peptide phage library was injected intravenously into the animals and synovial homing phage was recovered from grafts. DNA sequencing of homing phage clones allowed the identification of specific peptides.

Results

Synovial homing phages that distinctively bind to synovial but not skin or mouse MVE were isolated. They retained their tissue homing specificity in vivo independently from the phage component, the original pathology of the transplanted tissue and the degree of human/murine graft vascularisation. One such peptide (CKSTHDRLC) maintained synovial homing specificity both when presented by the phage or as a free synthetic peptide. The synthetic peptide also competed and inhibited in vivo the binding of the parent phage to the cognate synovial MVE ligand.

Conclusions

We report the isolation of peptides with homing properties specific for human synovial MVE. The identification of such peptides opens the possibility of using these sequences to construct joint-specific drug delivery systems that may have a considerable impact in the treatment of arthritic conditions.