We present the case of an adolescent who presented with rhabdomyolysis due to severe hypokalemia arising from chronic diarrhea. Initial evaluation for celiac disease, known to present in this manner, was negative. Fur...We present the case of an adolescent who presented with rhabdomyolysis due to severe hypokalemia arising from chronic diarrhea. Initial evaluation for celiac disease, known to present in this manner, was negative. Further evaluation with colonoscopy showed a normal appearing colon but biopsies showed a significant number of apoptotic cells in the mucosal crypts supporting a diagnosis of apoptotic colitis. Investigation into the cause of apoptotic colitis resulted in a diagnosis of common variable immune deficiency due to a defect in the inducible T-cell costimulator (ICOS) gene. Physicians should be aware of this uncommon condition and the importance of mucosal biopsy despite the presence of normal appearing mucosa.展开更多
Cytotoxic T cells targeting cancer neoantigens harboring driver mutations can lead to durable tumor regression in an HLAIdependent manner.However,it is difficult to extend the population of patients who are eligible f...Cytotoxic T cells targeting cancer neoantigens harboring driver mutations can lead to durable tumor regression in an HLAIdependent manner.However,it is difficult to extend the population of patients who are eligible for neoantigen-based immunotherapy,as immunogenic neoantigen-HLA pairs are rarely shared across different patients.Thus,a way to find other human leukocyte antigen(HLA)alleles that can also present a clinically effective neoantigen is needed.Recently,neoantigen-based immunotherapy targeting the KRAS G12D mutation in patients with HLA-C*08:02 has shown effectiveness.In a proof-ofconcept study,we proposed a combinatorial strategy(the combination of phylogenetic and structural analyses)to find potential HLA alleles that could also present KRAS G12D neoantigen.Compared to in silico binding prediction,this strategy avoids the uneven accuracy across different HLA alleles.Our findings extend the population of patients who are potentially eligible for immunotherapy targeting the KRAS G12D mutation.Additionally,we provide an alternative way to predict neoantigen-HLA pairs,which maximizes the clinical usage of shared neoantigens.展开更多
文摘We present the case of an adolescent who presented with rhabdomyolysis due to severe hypokalemia arising from chronic diarrhea. Initial evaluation for celiac disease, known to present in this manner, was negative. Further evaluation with colonoscopy showed a normal appearing colon but biopsies showed a significant number of apoptotic cells in the mucosal crypts supporting a diagnosis of apoptotic colitis. Investigation into the cause of apoptotic colitis resulted in a diagnosis of common variable immune deficiency due to a defect in the inducible T-cell costimulator (ICOS) gene. Physicians should be aware of this uncommon condition and the importance of mucosal biopsy despite the presence of normal appearing mucosa.
基金supported by the National Natural Science Foundation of China(31870728,31470738,and 32000611)the National Basic Research Program of China(2014CB910103)+1 种基金the Fundamental Research Funds for the Central Universities(2042020kfxg02)the China Postdoctoral Science Foundation(2018M642918)。
文摘Cytotoxic T cells targeting cancer neoantigens harboring driver mutations can lead to durable tumor regression in an HLAIdependent manner.However,it is difficult to extend the population of patients who are eligible for neoantigen-based immunotherapy,as immunogenic neoantigen-HLA pairs are rarely shared across different patients.Thus,a way to find other human leukocyte antigen(HLA)alleles that can also present a clinically effective neoantigen is needed.Recently,neoantigen-based immunotherapy targeting the KRAS G12D mutation in patients with HLA-C*08:02 has shown effectiveness.In a proof-ofconcept study,we proposed a combinatorial strategy(the combination of phylogenetic and structural analyses)to find potential HLA alleles that could also present KRAS G12D neoantigen.Compared to in silico binding prediction,this strategy avoids the uneven accuracy across different HLA alleles.Our findings extend the population of patients who are potentially eligible for immunotherapy targeting the KRAS G12D mutation.Additionally,we provide an alternative way to predict neoantigen-HLA pairs,which maximizes the clinical usage of shared neoantigens.
