biostudies-literatureUnknown14(1)Reschke R<h4>Background</h4>Immune checkpoint inhibitors have transformed melanoma therapy but frequently cause immune-related adverse events (irAEs), including colitis, that limit treatment. Reliable biomarkers predicting toxicity remain lacking.<h4>Methods</h4>In this retrospective, multicenter study, we analyzed pretreatment serum samples from 331 patients with metastatic melanoma treated with anti-CTLA-4 (ipilimumab), anti-PD-1 (pembrolizumab or nivolumab), or combination ipilimumab/nivolumab. IgG autoantibody reactivity against 832 human protein antigens, including autoimmune targets, cytokines, tumor-associated antigens, and cancer pathway proteins, was profiled using multiplex bead-based arrays. Statistical analysis (Significance Analysis of Microarrays and Cox regression) identified autoantJournal for immunotherapy of cancere013814https://www.ebi.ac.uk/biostudies/studies/S-EPMC12853468biostudies-literatureAutoantibodies as predictors for immune-related adverse events in checkpoint inhibition therapy of metastatic melanoma.PMC12853468Hassel JCDummer RPfoehler CSchulz CZucht HDGutjahr CHakim-Meibodi LEBudde PWeide BMangana JMeier FRichter JSchulz-Knappe PReschke RWistuba-Hamprecht KBrautigam MfalseAutoantibodies as predictors for immune-related adverse events in checkpoint inhibition therapy of metastatic melanoma.<h4>Background</h4>Immune checkpoint inhibitors have transformed melanoma therapy but frequently cause immune-related adverse events (irAEs), including colitis, that limit treatment. Reliable biomarkers predicting toxicity remain lacking.<h4>Methods</h4>In this retrospective, multicenter study, we analyzed pretreatment serum samples from 331 patients with metastatic melanoma treated with anti-CTLA-4 (ipilimumab), anti-PD-1 (pembrolizumab or nivolumab), or combination ipilimumab/nivolumab. IgG autoantibody reactivity against 832 human protein antigens, including autoimmune targets, cytokines, tumor-associated antigens, and cancer pathway proteins, was profiled using multiplex bead-based arrays. Statistical analysis (Significance Analysis of Microarrays and Cox regression) identified autoant2026-01-01T00:00:00Z2026 Jan2026-06-08T06:53:01.947Z2026-06-08T03:14:42.54ZS-EPMC128534684159289310.1136/jitc-2025-013814