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Impact of afatinib on intestinal and salivary IgA: Immune response alterations linked to gastrointestinal side
Ippei Uemura1, Natsuko Takahashi-Suzuki1, Takashi Satoh1
1Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Hokkaido University of Science, 7-Jo 15-4-1 Maeda, Teine-ku, Sapporo, Hokkaido 006-8585, Japan.
Background:
Afatinib, an oral molecular-targeted anticancer agent, is effective but causes significant gastrointestinal side effects. These effects are associated with EGFR inhibition in intestinal cells and changes in the microbiota.
Objective:
To investigate the effects of afatinib on intestinal mucosal immunity in rats, focusing on IgA levels in the intestine and saliva, and to understand the innate and acquired immune responses to these side effects.
Methods:
Male Wistar rats received afatinib (5.2 mg/kg) daily for 24 h (Day 1) and for 2 weeks (Day 14). Gene expression in the intestine was analyzed using quantitative polymerase chain reaction. IgA levels in the intestine and saliva were measured using enzyme-linked immunosorbent assay.
Results:
Afatinib suppressed α-defensin 5 and pIgR in the jejunum and ileum, indicating reduced innate immunity. It increased IgA levels in the intestine and saliva, suggesting altered acquired immunity. Salivary IgA levels significantly correlated with intestinal IgA levels.
Conclusions:
Afatinib affects gastrointestinal mucosal immunity, suppresses innate defense, and alters IgA production. Salivary IgA could serve as a marker for monitoring these effects, aiding cancer therapy management.
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