HLA-B*1502 is associated with aromatic anticonvulsant drug-induced cutaneous adverse drug reactions among the Hakka population in China
JOURNAL OF INTERNATIONAL MEDICAL RESEARCH
Authors: Zheng, Zhiyuan; Zhong, Hua; Zhang, Qunji; Huang, Qingyan; Wu, Heming
Abstract
Background The purpose of this study was to analyze the correlation between aromatic antiepileptic drug-induced cutaneous adverse drug reactions and HLA-B*1502 genotype in patients from the Hakka population in Meizhou. Methods A total of 214 epileptic patients taking aromatic (n = 94) or non-aromatic anticonvulsants (n = 120) were included in the study from September 2016 to May 2018. Clinical data for the patients were analyzed retrospectively and HLA-B*1502 genotype testing was carried out. Results Thirty patients were HLA-B*1502(+) (14.02%). The proportion of HLA-B*1502(-) genotype and incidence of adverse drug reactions (ADRs) differed significantly between the two drug groups. In the aromatic anticonvulsant group, maculopapular eruption (MPE), Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and hypersensitivity syndrome (HSS) occurred in 10 patients, including eight HLA-B*1502(+) and two HLA-B*1502(-) patients. MPE, HSS, SJS, and TEN occurred in 26 patients in the non-aromatic anticonvulsant group, including one HLA-B*1502(+) and 25 HLA-B*1502(-) patients. There was a significant correlation between the proportions of HLA-B*1502(+) genotype and induced cutaneous adverse drug reactions in the two groups. Conclusions HLA-B*1502 is associated with aromatic anticonvulsant drug-induced cutaneous adverse drug reactions among the Hakka population in Meizhou, China.
Co-expression of HLA-I loci improved prognostication in HER2+breast cancers
CANCER IMMUNOLOGY IMMUNOTHERAPY
Authors: Tsang, Julia Y.; Ho, Chun-Sing; Ni, Yun-Bi; Shao, Yan; Poon, Ivan K.; Chan, Siu-Ki; Cheung, Sai-Yin; Shea, Ka-Ho; Marabi, Monalyn; Tse, Gary M.
Abstract
The underlying basis for cancer immune evasion is important for effective immunotherapy and prognosis in breast cancers. Human leucocyte antigens (HLA)-I comprising three classical antigens (HLA-A, -B and -C) is mandatory for anti-tumor immunity. Its loss occurred frequently in many cancers resulting in effective immune evasion. Most studies examined HLA-I as a whole. Alterations in specific locus could have different clinical ramifications. Hence, we evaluated the expression of the three HLA-I loci in a large cohort of breast cancers. Low expression of HLA-A, -B and -C were found in 71.1%, 66.3%, and 60.2% of the cases. Low and high expression in all loci was found in 48.3% and 17.9% of the cases respectively. The remaining showed high expression in one or two loci. Cases with all HLA high expression (all HLA high) was frequent in the ER-HER2- (27.4%) and ER-HER2+ (23.1%) cases and was associated with characteristic pathologic features related to these tumor (higher grade, necrosis, high tumor infiltrating lymphocyte (TIL), pT stage, low hormonal receptor, high basal marker expression) (p <= 0.019). Interestingly, in HER2+ cancers, only cases with all HLA high and high TIL showed significantly better survival. In node positive cancers, concordant high HLA expression in primary tumors and nodal metastases was favorable prognostically (DFS: HR = 0.741, p < 0.001; BCSS: HR = 0.699, p = 0.003). The data suggested an important clinical value of a combined analysis on the co-expression HLA-I status in both primary and metastatic tumors. This could be a potential additional key component to be incorporated into TIL evaluation for improved prognostication.