Author:
Genta Sofia,Lajkosz Katherine,Yee Noelle R.,Spiliopoulou Pavlina,Heirali Alya,Hansen Aaron R.,Siu Lillian L.,Saibil Sam,Stayner Lee-Anne,Yanekina Maryia,Sauder Maxwell B.,Keshavarzi Sareh,Salawu Abdulazeez,Vornicova Olga,Butler Marcus O.,Bedard Philippe L.,Razak Albiruni R. Abdul,Rottapel Robert,Chruscinski Andrzej,Coburn Bryan,Spreafico Anna
Abstract
Abstract
Background
Immune-checkpoint inhibitors (ICI) can lead to immune-related adverse events (irAEs) in a significant proportion of patients. The mechanisms underlying irAEs development are mostly unknown 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 patients receiving ICI. Plasma was collected before and after ICI from cancer patients participating in two clinical trials (NCT03686202, NCT02644369). A one-time collection was obtained from healthy controls for comparison. Custom arrays with 162 autoAg were used to detect IgG and IgM reactivities. Differences of median fluorescent intensity (MFI) were analyzed with Wilcoxon sign rank test and Kruskal–Wallis test. MFI 500 was used as threshold to define autoAb reactivity.
Results
A total of 114 patients and 14 healthy controls were included in this study. irAEs of grade (G) ≥ 2 occurred in 37/114 patients (32%). We observed a greater number of IgG and IgM reactivities in pre-ICI collections from patients versus healthy controls (62 vs 32 p < 0.001). Patients experiencing irAEs G ≥ 2 demonstrated pre-ICI IgG reactivity to a greater number of AutoAg than patients who did not develop irAEs (39 vs 33 p = 0.040). We observed post-treatment increase of IgM reactivities in subjects experiencing irAEs G ≥ 2 (29 vs 35, p = 0.021) and a decrease of IgG levels after steroids (38 vs 28, p = 0.009).
Conclusions
Overall, these results support the potential role of autoAb in irAEs etiology and evolution. A prospective study is ongoing to validate our findings (NCT04107311).
Funder
Novartis Young Canadian Investigator Award
Dr. Spreafico Research Found
Publisher
Springer Science and Business Media LLC
Cited by
1 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献