The Anti-Il-13 Biologic Tralokinumab Did Not Alter Expression of T2 and T17 Transcription Factors GATA3 and RORyT in Bronchial Biopsies

Background: Type 2 (T2) and Type 17 (T17) inflammation is reported to be reciprocally regulated in asthma [1]. The anti-IL-13 biologic tralokinumab reduced FeNO and IgE in asthma [2] suggesting it attenuated T2 inflammation, but its effect on T17 immunity are unknown. Aims: We hypothesized that the number of cells in bronchial biopsies expressing the T2 or T17 transcription factors Gata binding protein 3 (GATA3) and RAR-related orphan receptor gamma (RORγt) would decrease and increase reciprocally following treatment with tralokinumab vs. placebo. Methods: We retrospectively selected subjects from the MESOS trial (NCT02449473) who had received tralokinumab with a reduction in FeNO >5ppb (n=20) or placebo with ≤5ppb change in FeNO (n=20). Bronchial biopsy expression of GATA3 and RORγt positive cells in the lamina propria was assessed using RNAscope. Results: Median [IQR] cells/mm2 at baseline were 24.2 [7.4-49.2] and 7.1 [3.5-10.0] for GATA3 and RORγt respectively. There was no significant change in expression of these transcription factors following treatment with tralokinumab or placebo. GATA3 and RORγt change from baseline was positively correlated (r=0.52; p=0.0007). No correlations were seen between GATA3 or RORγt expression and baseline blood or tissue eosinophils, FeNO, or IgE. Conclusion: The number of cells expressing T2 and T17 transcription factors did not change following anti-IL-13 treatment with tralokinumab. Whether this is reflected in T2/T17 gene signatures following tralokinumab treatment needs investigation. References: 1) Choy et al. Sci Transl Med. 2015;7(301):301ra129 2) Russell et al. Lancet Respir Med. 2018 Jul;6(7):499-510 Funding support: AstraZeneca