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We investigated whether humoral immunity is associated with subsequent severe immune-related colitis (irC). In melanoma patients, baseline serum autoantibody (AAb) profiling identified a composite antigen signature - a signature-level association rather than validated functional specificities - associated with severe irC, marked by retained reactivity to tumor-associated antigens and relative depletion of antibodies recognizing immune- and mucosal-regulatory proteins. To assess functional relevance, we transferred polyclonal IgG from severe- or non-severe-irC patients into wild-type or humanized Fc\u03b3 receptor (hFc\u03b3R) mice treated with anti-PD-1 or anti-CTLA-4. IgG alone did not induce inflammation; however, severe- irC IgG amplified checkpoint-driven colonic inflammation in hFc\u03b3R mice, but not in wild-type mice, with checkpoint-specific remodeling of myeloid, lymphoid, and innate lymphoid compartments. These findings suggest that pretreatment humoral immunity conditions susceptibility to irC via the IgG-Fc\u03b3R axis.<\/jats:p>\n                <jats:sec>\n                  <jats:title>Statement of Significance<\/jats:title>\n                  <jats:p>Pretreatment autoantibody signatures represent host humoral states associated with risk of severe immune checkpoint inhibitor-associated colitis. Patient-derived polyclonal IgG amplified checkpoint-driven intestinal inflammation through Fc\u03b3R-dependent mechanisms without independently inducing disease, supporting the IgG-Fc\u03b3R axis as a candidate pathway for mechanistic study and toxicity-risk stratification.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.06.03.729692","type":"posted-content","created":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T05:05:39Z","timestamp":1780895139000},"source":"Crossref","is-referenced-by-count":0,"title":["Patient-derived IgG Amplifies Fc\u03b3 Receptor-Dependent Colonic Inflammation During Immune Checkpoint Blockade"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5975-8463","authenticated-orcid":false,"given":"Iryna","family":"Voloshyna","sequence":"first","affiliation":[{"name":"Laura and Isaac Perlmutter Cancer Center, New York University Grossman School of Medicine, New York, NY 10016, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yury","family":"Patskovsky","sequence":"additional","affiliation":[{"name":"Laura and Isaac Perlmutter Cancer Center, New York University Grossman School of Medicine, New York, NY 10016, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabina","family":"Sandigursky","sequence":"additional","affiliation":[{"name":"Laura and Isaac Perlmutter Cancer Center, New York University Grossman School of Medicine, New York, NY 10016, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaitra","family":"Sreenivasaiah","sequence":"additional","affiliation":[{"name":"Applied Bioinformatics Laboratories, New York University Langone Medical Center, New York, NY, 10016, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erol C.","family":"Bayraktar","sequence":"additional","affiliation":[{"name":"Department of Pathology, New York University Grossman School of Medicine, New York, NY, 10016, USA"},{"name":"Ronald O. 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