This study identified a novel class of autoantibodies in psoriatic arthritis (PsA) that target SOX-D transcription factors—specifically SOX5, SOX6, and SOX13—with the most detailed analysis focused on SOX5. Anti-SOX5 antibodies were more frequently found in women with PsA, particularly those with guttate psoriasis and prior TNF inhibitor exposure. These antibodies were also present at lower frequencies in patients with psoriasis without arthritis, rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE). In a subset of patients with PsA with longitudinal data, anti-SOX5 positivity was associated with a higher likelihood of biologic DMARD use and showed evidence of differential treatment response—particularly greater fatigue improvement with IL-17 inhibitors and less benefit from IL-12/23 inhibitors.

These findings suggest that anti-SOX5 antibodies may help define a clinically meaningful and mechanistically distinct subgroup within psoriatic disease, especially among women. Although no correlation was found between antibody levels and TNF-α or IL-17A cytokine levels, the consistent associations with treatment patterns and outcomes suggest a potential role in guiding therapeutic decisions. Additionally, the study validated the presence of anti–ADAMTS-L5 antibodies in PsA, reinforcing their relevance in psoriatic autoimmunity. Together, the identification of SOX-D autoantibodies—particularly SOX5—adds to the growing understanding of psoriatic disease heterogeneity and may contribute to more individualized treatment strategies in the future.

Reference: Orbai AM, Fiorentino D, Perin J, et al. SOX-5 Transcription Factor: a Novel Psoriatic Autoantigen Preferentially Found in Women. ACR Open Rheumatol. 2024 Dec;6(12):807-819. doi: 10.1002/acr2.11740. Epub 2024 Sep 1. PMID: 39218617; PMCID: PMC11638130.