The Application Value Of 2D-SWE Technology In The Adverse Reactions Of Thyroid Immunity Induced By PD-1 Inhibitor In Rabbits

Objective:To observe the effect of programmed death receptor 1(PD-1)inhibitor on normal rabbit thyroid using two-dimensional shear wave elastography(2D-SWE),and to compare it with the changes in thyroid function and pathological changes,to explore the development process of thyroid immune-related adverse events(irAEs)induced by PD-1 inhibitor in rabbits and the application value of 2D-SWE technology in rabbit thyroid irAEs induced by PD-1 inhibitor.Methods:Forty-five male New Zealand white rabbits were randomly divided into 2 groups,namely the control group(n=20)and the experimental group(n=25).The experimental group was given toripalimab(PD-1 inhibitor)every 14 days(15mg/kg)with an appropriate amount of normal saline was infused via the ear vein,and the control group was given the same amount of normal saline every 14 days by infusion via the ear vein.The rabbits in the experimental group and the control group were treated with pre-administration(TO stages),the 14th day after the first administration(T1 stages),the 14th day after the second administration(T2 stages),and the 14th day after the third administration(T3 stages),the 14th day after the fourth administration(T4 stages),routine ultrasound was used to observe or measure the changes of the shape、size and Color Doppler Imaging of thyroid glands in the experimental group and control group.The 2D-SWE technique was used to measure the Young’s modles of the rabbit thyroid gland simultaneously and recorded.At the same time,the venous blood of the rabbits in the experimental group was drawn from the ear vein to test the thyroid function.InT0,T1,T2,T3 and T4 stages,2 rabbits in each experimental group and 1 rabbit in the control group were randomly selected to be sacrificed by air embolization,pathological biopsy was performed,and observe the pathological changes.Statistical analysis was performed on the differences between the parameters and the different periods within the group.Result:1 Survival of experimental rabbitsThere was no accidental death in the control group in the whole cycle,and 3 rabbits in the experimental group died unexpectedly,2 died in T3 stage and 1 died in T4 stage respectively.2 UltrasoundThere was no significant difference in the morphology,size and color Doppler imaging of the thyroid between the experimental group rabbits and the control group rabbits at T0,T1,T2,T3 and T4 stages.Comparing the Young’s modles between the experimental group and the control group,there was no significant difference in TO and T1 stages(P>0.05);but the differences in T2,T3,and T4 stages were all statistically significant(P<0.05).In the experimental group,there was no significant difference in Young’s modles between TO and T1 stages,T1 and T2stages(P>0.05),but there was significant difference in the other stages(P<0.05).3 Thyroid functionThere were statistically significant differences between TO and T2,T2 and T3,and T2 and T4 thyroid free T3(FT3)and free T4(FT4)in the experimental group(P<0.05),but there was no significant difference in the rest of the group(P>0.05).Compared with T3 and T4 hypersensitivity thyroid-stimulating hormone(hTSH)in the experimental group in T0,T1 and T2 stages respectively,the differences were statistically significant(P<0.05),and there was no significant difference in the rest of the group(P>0.05).The Young’s modles of rabbits in the experimental group had a linear positive correlation with hTSH(r=0.690,P<0.001),but there was no significant linear correlation with FT3 and FT4.Because the test results of thyroglobulin antibody(TGAb)and thyroid peroxidase antibody(TPOAb)were both within an approximate numerical range,and the T0 to T4 stages were all within this range,so they were not included in the statistical analysis.4 PathologicalThe shape and size of thyroid follicles and epithelial cells in the control group were normal,and there was no obvious lymphocyte infiltration and interstitial fibrosis.In the experimental group,the morphology of thyroid follicles in T0 stage was normal,with individual lymphocyte infiltration and no obvious interstitial fibrosis;in T1 stage,the shape of thyroid follicles was normal,with scattered lymphocyte infiltration and no obvious interstitial fibrosis;in T2 stage,thyroid follicles had normal shape There is a little lymphocyte infiltration,but the interstitial fibrosis is not obvious;in T3 stage,thyroid lymphocyte infiltration increased,and interstitial fibrosis was more obvious.In T4 stage,the size of thyroid follicles varied,more lymphocytes infiltrated in the interstitium,and fibrosis was more obvious.Conclusion:1 The model of rabbit thyroid irAEs was successfully established by infusion of PD-1 inhibitor.2 During the administration of PD-1 inhibitor,the thyroid function of rabbits changed,and the hardness of thyroid gland increased gradually,that is,PD-1 inhibitor led to the occurrence of thyroid irAEs.3 2D-SWE technology has a good evaluation value in thyroid irAEs,and can monitor the changes or progress of thyroid irAEs in combination with thyroid function tests.