دورية أكاديمية

Autoimmune PaneLs as PrEdictors of Toxicity in Patients TReated with Immune Checkpoint InhibiTors (ALERT)

التفاصيل البيبلوغرافية
العنوان: Autoimmune PaneLs as PrEdictors of Toxicity in Patients TReated with Immune Checkpoint InhibiTors (ALERT)
المؤلفون: 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
المساهمون: Novartis Young Canadian Investigator Award, Dr. Spreafico Research Found
المصدر: Journal of Experimental & Clinical Cancer Research ; volume 42, issue 1 ; ISSN 1756-9966
بيانات النشر: Springer Science and Business Media LLC
سنة النشر: 2023
مصطلحات موضوعية: Cancer Research, Oncology
الوصف: 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).
نوع الوثيقة: article in journal/newspaper
اللغة: English
DOI: 10.1186/s13046-023-02851-6
DOI: 10.1186/s13046-023-02851-6.pdf
DOI: 10.1186/s13046-023-02851-6/fulltext.html
الإتاحة: https://doi.org/10.1186/s13046-023-02851-6Test
حقوق: https://creativecommons.org/licenses/by/4.0Test ; https://creativecommons.org/licenses/by/4.0Test
رقم الانضمام: edsbas.B9FDA2BD
قاعدة البيانات: BASE