Lillian L Siu: manuscript revision. GUID:?1F18E444-5C01-401B-AD0C-A85D30286995 BII Additional file 8: Supplementary Fig. 1. Frequencies of different irAEs G2. 13046_2023_2851_MOESM8_ESM.docx (45K) GUID:?E88B4112-DF4F-40C3-B2A0-0D20890B8494 Additional file 9: Supplementary Fig. 2. Changes in IgM and IgG levels in 61 individuals without irAEs from baseline (pre-ICI collection) to the 1st collection after ICI administration. 13046_2023_2851_MOESM9_ESM.docx (58K) GUID:?B88E89E4-5088-4FAF-9C3B-8AF8B0907640 Additional file 10: Supplementary Fig. 3. Dynamic changes of autoAbs in individuals with and without irAEs G2. 13046_2023_2851_MOESM10_ESM.docx (79K) GUID:?C43A7B27-11C3-4670-8D78-31FF7B491D48 Additional file 11: Supplementary Fig. 4. Assessment of the level of IgM and IgG with MFI> 500 at the time of irAEs and post steroids administration in 9 individuals. 13046_2023_2851_MOESM11_ESM.docx (30K) GUID:?3CA99606-0498-443F-A25F-DA7F9DC98351 Additional file 12: Supplementary Fig. 5. Assessment of AutoAbs levels measured with ELISA in individuals with and without irAEs G2 and dynamic changes in individuals who developed irAEs G>2. 13046_2023_2851_MOESM12_ESM.docx (46K) GUID:?41AC0CD6-12FC-4B4F-B505-2AE31ED2F94D Data Cyclosporine Availability Cyclosporine StatementData supporting this study are included in the article and/or in the supporting materials. Abstract Background Immune-checkpoint inhibitors (ICI) can lead to immune-related adverse events (irAEs) in a significant proportion of individuals. The mechanisms underlying irAEs development are mostly unfamiliar and might involve multiple immune effectors, such as T cells, B cells and autoantibodies (AutoAb). Methods We used custom autoantigen (AutoAg) microarrays to profile AutoAb related to irAEs in individuals receiving ICI. Plasma was collected before and after ICI from malignancy individuals participating in two medical tests (NCT03686202, NCT02644369). A one-time collection was from healthy controls for assessment. Custom arrays with 162 autoAg were used to detect IgG and IgM reactivities. Variations of median fluorescent intensity (MFI) were analyzed with Wilcoxon sign rank test and KruskalCWallis Cyclosporine test. MFI 500 was used as threshold to determine autoAb reactivity. Results A total of 114 individuals and 14 healthy settings were included in this study. irAEs of grade (G)??2 occurred in 37/114 individuals (32%). We observed a greater number of IgG and IgM reactivities in pre-ICI selections from individuals versus healthy settings (62 vs 32 head and neck squamous cell malignancy, immune-related adverse events, not relevant, triple negative breast malignancy *No significant changes were observed in the number of AutoAb reactivities pre- and post-ICI in individuals who did not develop G??2 irAEs (median 60 vs 58, Additionally, no significant differences in the median MFI for each specific AutoAg were observed between individuals with and without history of autoimmune disorders (Supplementary Table 5). We did not observe a correlation between a specific toxicity and high reactivity against a certain AutoAg (Supplementary Table 6). However, in some individuals who experienced organ-specific irAEs we observed pre-ICI high levels of AutoAb against the related cells. For instance, we recognized high levels of IgG anti cardiac myosin before ICI exposure in a patient who consequently experienced immune related myocarditis and very high pre-ICI levels of IgG anti-desmin in a patient who experienced colitis. Baseline and post-ICI reactivity of organ-specific AutoAb in selected individuals, compared with median ideals in healthy controls and in all the individuals before ICI exposure are reported in Supplementary Table 7. No difference in the level of IgG and IgM measured by ELISA is definitely observed between individuals with and without irAEs We compared the value of total IgM and IgG measured by ELISA in the pre- and post-ICI samples from individuals with and without G??2 irAEs. No variations were observed at baseline between individuals with and without irAEs G??2 (median IgM value 3.47?g/L vs 2.88?g/L, (Supplementary Fig.?5). Conversation The relationship between malignancy and immune system is only partially understood. The recognition of reliable factors to distinguish upfront subjects.