Study On The Correlation Between Lamotrigine-induced Cutaneous Adverse Reactions And TCRBV Genes Expression

Objective To investigate the possible pathogenesis mechanism of lamotrigine(LTG)-induced T cell-mediated immune response which caused cutaneous adverse reactions(cADRs).The differences in TCRBV genes expression were analyzed between LTG-cARDs patients and LTG tolerant patients in their peripheral blood mononuclear cells(PBMCs).To investigate the correlation between LTG-cADRs and TCRBV genes expression.Materials and methods Collected 10 cases of cARDs had been cured for more than 6weeks of LTG-cADRs patients as a case group,10 cases of LTG tolerant were included as the control group by 1:1 match(according to the case-control study).Separating the PBMCs of these two groups,and giving LTG in vitro stimulation and culture.The levels of IFN-?,IL-5and TNF-? which secreted by PBMCs in patients with case group and control group were measured by ELISA.The expression of TCRBV genes was detected by SYBR Green?fluorescent dye method using quantitative real-time reverse transcription(RT-qPCR).The differences in IFN-?,IL-5 and TNF-? concentrations between two groups were compared by two independent samples t or t'.The relative expression of TCRBV genes in case group and control group was calculated by 2-??Ct relative quantification method.The differences of TCRBV genes expression between case group and control group was analyzed by Mann-Whitney U test.Results The PBMCs of the case group and the control group were stimulated with LTG at the final concentration of 25?g/ml,the concentration of IFN-?(1.06±0.09ng/ml)in the supernatant of case group was significantly higher than that in the control group(0.86±0.16ng/ml),the difference was statistically significant(P<0.05).The concentrations ofIL-5 and TNF-?(0.73±0.06ng/ml,0.69±0.05ng/ml)in the supernatant of the case group was slightly higher than that in the control group(0.70±0.07ng/ml,0.65±0.05ng/ml),the difference was not statistically significant(P>0.05).There was a significant difference in TCRBV genes expression between case group and control group.The relative expression of TCRBV11,TCRBV15,TCRBV17,TCRBV18 and TCRBV19 in the case group was higher than that in the control group(P<0.05).Conclusions 1.LTG can activate PBMCs in LTG-cARDs patients in vitro,which can secret IFN-?,suggesting that immune responses mediated by T cell may be involved in the pathogenesis of LTG-cADRs.2.As likely as not,LTG-cADRs are associated with the expression of genes of TCRBV11,TCRBV15,TCRBV17,TCRBV18 and TCRBV19.