ADAMTS-like protein 5 (ADAMTSL5) is a melanocyte-derived auto-antigen in psoriasis

Psoriasis is a chronic skin inflammatory disorder characterized by thickening of skin epidermal layer. Psoriasis is considered autoimmune diseases due to presence of activated T cells within epidermal layer in affected skin and clinical benefits of antibody therapy directed against cytokines such as IL-23 and IL-17. However, the exact (auto)antigen[s] targeted by T cells are not well known.

This short paper from Journal of Experimental Medicine suggests that a disintegrin and metalloprotease with thrombospondin motifs-like-5 protein (ADAMTSL5) expressed by melanocytes is a psoriasis-specific auto-antigen.

This study is continuation of earlier studies showing that (a) HLA-C*06:02 allele occurs in more than 60% of psoriatic patients, and (b) psoriatic lesion contains high frequency of Vα3S1⁺/Vβ13S1⁺ CD8 T cells. Now, using in vitro HLA transfection experiments the authors showed that Vα3S1⁺/Vβ13S1⁺ T hybridoma recognized HLA-C*06:02⁺melanocytes [but not keratinocytes or fibroblasts] in a HLA I-specific manner.

Next, using bioinformatics approach in combination with in vitro hybridoma activation assay (NF-κB-GFP readout), the authors identified ADAMTS-like protein 5 (ADAMTSL5) as a potential auto-antigen in psoriasis.

ADAMTSL5 was highyl expressed by both primary and cell line melanocytes (WM278).

Finally, the authors showed that ADAMTSL5 derived peptide stimulated psoriatic T cells but not T cells from healthy individuals.

In summary, this study showed that melanocyte-derived ADAMTSL5 represents auto-antigen in psoriasis. The authors claim that this is a first definitive report of showing psoriasis as a truly autoimmune diseases.

David Usharauli