Distinct patterns of auto-reactive antibodies associated with organ-specific immune-related adverse events.

The roles of preexisting auto-reactive antibodies in immune-related adverse events (irAEs) associated with immune checkpoint inhibitor therapy are not well defined. Here, we analyzed plasma samples longitudinally collected at predefined time points and at the time of irAEs from 58 patients with immunotherapy naïve metastatic non-small cell lung cancer treated on clinical protocol with ipilimumab and nivolumab. We used a proteomic microarray system capable of assaying antibody reactivity for IgG and IgM fractions against 120 antigens for systemically evaluating the correlations between auto-reactive antibodies and certain organ-specific irAEs. We found that distinct patterns of auto-reactive antibodies at baseline were associated with the subsequent development of organ-specific irAEs. Notably, ACHRG IgM was associated with pneumonitis, anti-cytokeratin 19 IgM with dermatitis, and anti-thyroglobulin IgG with hepatitis. These antibodies merit further investigation as potential biomarkers for identifying high-risk populations for irAEs and/or monitoring irAEs during immunotherapy treatment. ClinicalTrials.gov identifier: NCT03391869.

Informations de copyright

Copyright © 2023 Altan, Li, Wang, Vokes, Sheshadri, Gao, Zhu, Tran, Gandhi, Antonoff, Swisher, Wang, Byers, Abdel-Wahab, Franco-Vega, Wang, Lee, Zhang and Heymach.

Déclaration de conflit d'intérêts

Outside of the submitted work MA reports receiving research funding to institution from Genentech, Nektar Therapeutics, Merck, GlaxoSmithKline, Novartis, Jounce Therapeutics, Bristol Myers Squibb, Eli Lilly, Adaptimmune, Shattuck Lab, and receives consultant and advisor fees from GlaxoSmithKline, Bristol Myers Squibb, Shattuck Lab and AstraZeneca, Speaker fees: AstraZeneca, Nektar Therapeutics, SITC, Participation of Safety review committee for Nanobiotix-MDA alliance, Hengenix outside of the submitted work; NV reports receiving research funding to institution: Mirati, Circulogene and receives consultant fees from Sanofi, Regeneron, Eli Lilly, OncoCyte; JG reports consulting/advisory committee fees from CRISPR Therapeutics, Jounce Therapeutics, Polaris, Seagen, AstraZeneca, Aveo Pharmaceuticals, Infinity Pharmaceuticals, Janssen, Pfizer, and Symphogen; SG reports receiving research funding to institution from Bristol Myers Squibb; MBA reports consulting fees from Astra Zeneca; LB reports receiving research funding to institution AstraZeneca, Amgen, Jazz Pharmaceuticals, reports consulting/advisory committee fees from for AstraZeneca, AbbVie, Arrowhead Pharmaceuticals, Genetech, AbbVie, Merck, Jazz Pharmaceuticals, BeiGene, Chugai Pharmaceuticals, Puma, Amgen, Daiichi Sankyo; JZ reports grants from Merck, grants and personal fees from Johnson and Johnson and Novartis, personal fees from Bristol Myers Squibb, AstraZeneca, GenePlus, Innovent and Hengrui; JH has served on the scientific advisory boards for AstraZeneca, Biotree, Bristol-Myers Squibb, Boehringer Ingelheim, Catalyst, EMD Serono, Genentech, GlaxoSmithKline, Guardant Health, Hengrui, Eli Lilly, Novartis, Seattle Genetics, Spectrum, Synta, Foundation Medicine, Takeda, Mirati Therapeutics, BrightPath Biotherapeutics, Janssen Global Services, Nexus Health Systems, Pneuma Respiratory, Kairos Venture Investments, Roche, and Leads Biolabs. He receives research support from AstraZeneca, Bayer, GlaxoSmithKline, Spectrum, and Takeda, and royalties and licensing fees from Spectrum. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.