{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T21:13:12Z","timestamp":1768511592151,"version":"3.49.0"},"posted":{"date-parts":[[2024,4,29]]},"group-title":"Immunology","reference-count":27,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,4,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>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.<\/jats:p>","DOI":"10.1101\/2024.04.26.591387","type":"posted-content","created":{"date-parts":[[2024,4,29]],"date-time":"2024-04-29T18:40:22Z","timestamp":1714416022000},"source":"Crossref","is-referenced-by-count":0,"title":["IL-12\/IL23 blockade reveals patterns of asynchronous inflammation in pyoderma gangrenosum"],"prefix":"10.64898","author":[{"given":"Rashi","family":"Yadav","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Morgan","family":"Vague","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Malia","family":"Rettig","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher P.","family":"Loo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kasidy","family":"Brown","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abrar","family":"Samiea","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joshua M.","family":"Moreau","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alex G","family":"Ortega-Loayza","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"issue":"1","key":"2024050300051400000_2024.04.26.591387v1.1","doi-asserted-by":"crossref","first-page":"4919","DOI":"10.1038\/s41598-023-31914-z","article-title":"Different molecular pathways are disrupted in Pyoderma gangrenosum patients and are associated with the severity of the disease","volume":"13","year":"2023","journal-title":"Sci Rep"},{"issue":"1","key":"2024050300051400000_2024.04.26.591387v1.2","first-page":"37","article-title":"Pyoderma gangrenosum. 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