IL-12/IL23 blockade reveals patterns of asynchronous inflammation in pyoderma gangrenosum

Yadav, R.; Vague, M.; Rettig, M.; Loo, C. P.; Brown, K.; Samiea, A.; Moreau, J. M.; Ortega-Loayza, A. G.

doi:10.1101/2024.04.26.591387

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bioRxiv · 10.1101/2024.04.26.591387

IL-12/IL23 blockade reveals patterns of asynchronous inflammation in pyoderma gangrenosum

Yadav, R.·Vague, M.·Rettig, M.·Loo, C. P.·Brown, K.·Samiea, A.·Moreau, J. M.·Ortega-Loayza, A. G.

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Abstract

Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis causing chronic and recalcitrant painful ulcerations. Pathogenic mechanisms are yet poorly understood limiting therapeutic options, however, IL-12/IL-23 inhibition via ustekinumab has previously been associated with positive outcomes. We aimed to elucidate the dysregulated immune landscape of PG and lesional skin changes associated with IL-12/IL-23 blockade. We applied spatial transcriptomics and comparative computation analysis on lesional biopsies from two patients obtained before and after IL-12/IL-23 blockade with ustekinumab. Our data indicate lesional PG skin exhibits complex patterns of inflammation, including a not previously described major infiltration of B cells and establishment of tertiary lymphoid structures. In both patients, IL-12/IL-23 blockade led to marked clinical improvement but was associated with amelioration of contrasting inflammatory pathways. Notably, plasma cell markers and tertiary structures were recalcitrant to the treatment regime suggesting that B cells might play a role in the refractory nature of PG.

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Yadav, R., Vague, M., Rettig, M., Loo, C. P., Brown, K., Samiea, A., Moreau, J. M., Ortega-Loayza, A. G.. 2024-04-29. IL-12/IL23 blockade reveals patterns of asynchronous inflammation in pyoderma gangrenosum. https://doi.org/10.1101/2024.04.26.591387

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