Siglec-9 antibodies(Palleon Pharma)

Sialic acid‐binding Ig‐like lectin‐9 (Siglec‐9) is a novel sialic acid‐binding member of the immunoglobulin superfamily and is broadly expressed on immune cells, which can inhibit both innate and adaptive immune responses through immunoreceptor tyrosine‐based inhibitory motifs. However, the exact role of Siglec‐9 in the pathogenesis of rheumatoid arthritis (RA) remains unknown. In this study, we determined soluble Siglec‐9 (sSiglec‐9) levels in the serum and synovial fluid of patients with RA and evaluated the relation between sSiglec‐9 levels and clinical factors. In addition, we investigated whether Siglec‐9 could alleviate collagen‐induced arthritis (CIA) development in mice and explored the molecular mechanisms involved. The results showed that, in the serum and synovial fluid of patients with RA, sSiglec‐9 levels were elevated. Thus, high sSiglec‐9 serum levels associated with disease severity in patients with RA. Furthermore, administration of recombinant human Siglec‐9 Fc chimera protein significantly attenuated collagen‐induced arthritis development in vivo and in vitro by reciprocal regulation of the differentiation of Th17 and Treg cells. Our findings collectively indicate that Siglec‐9 plays a potent immunosuppressive role in the pathogenesis of RA by reciprocal regulation of Th17‐/Treg‐cell differentiation. In conclusion, Siglec‐9 may serve as a potential diagnostic and therapeutic target for RA.

Human primary amine oxidase (hAOC3), also known as vascular adhesion protein 1, mediates leukocyte rolling and trafficking to sites of inflammation by a multistep adhesion cascade. hAOC3 is absent on the endothelium of normal tissues and is kept upregulated during inflammatory conditions, which is an applicable advantage for imaging inflammatory diseases. Sialic acid binding immunoglobulin like-lectin 9 (Siglec-9) is a leukocyte ligand for hAOC3. The peptide (CARLSLSWRGLTLCPSK) based on the region of Siglec-9 that interacts with hAOC3, can be used as a specific tracer for hAOC3-targeted imaging of inflammation using Positron Emission Tomography (PET). In the present study, we show that the Siglec-9 peptide binds to hAOC3 and triggers its amine oxidase activity towards benzylamine. Furthermore, the hAOC3 inhibitors semicarbazide and imidazole reduce the binding of wild type and Arg/Ala mutated Siglec-9 peptides to hAOC3. Molecular docking of the Siglec-9 peptide is in accordance with the experimental results and predicts that the R3 residue in the peptide interacts in the catalytic site of hAOC3 when the topaquinone cofactor is in the non-catalytic on-copper conformation. The predicted binding mode of Siglec-9 peptide to hAOC3 is supported by the PET studies using rodent, rabbit and pig AOC3 proteins.