Immunopeptidome analysis reveals SERPINB3 as an autoantigen driving eczematized psoriasis

Psoriasis (Pso) is a chronic inflammatory skin disease driven by T helper 17 (T(H)17) cells, with several clinical subtypes. While self-reactive immune responses have been observed, the role of autoantigens in Pso remains unclear. Using immunopeptidomics, we identified serpin family B member 3 (SERPINB3) and SERPINB4 as candidate autoantigens in Pso skin. In a mouse model, the SERPINB3 ortholog Serpinb3b enhanced inflammation, promoted tissue-resident memory T cells, and skewed immunity toward a T(H)2 phenotype. In humans, SERPINB3 reactivity was specifically associated with "eczematized psoriasis" (EczPso), a subtype marked by T(H)2/T(H)17 immune signatures. SERPINB3 protein was enriched in EczPso lesions and highly secreted by keratinocytes under combined T(H)2/T(H)17 stimulation. Lesional T cells from EczPso-but not from eczema or classical plaque Pso-proliferated in response to SERPINB3 and induced EczPso-like features in a skin model. Our findings identify SERPINB3 as an autoantigen driving a distinct Pso subtype, supporting more precise diagnosis and therapy.

• Jargosch, M.
• Kuruvila, J.
• Scala, E.
• Grosch, J.
• Eigemann, J.
• Wasserer, S.
• Lekiashvili, S.
• Trautwein, N.
• Kowalewski, D. J.
• Böhner, A.
• Köseoglu, Y.
• Hillig, C.
• Thomas, J.
• Lauffer, F.
• Schmidt-Weber, C. B.
• Menden, M. P.
• Walz, J. S.
• Kaesler, S.
• Eyerich, S.
• Blank, S.
• Rammensee, H. G.
• Biedermann, T.
• Eyerich, K.
• Kurgyis, Z.
• Freudenmann, L. K.
• Garzorz-Stark, N.