Adults with septic shock and extreme hyperferritinemia exhibit pathogenic immune variation.
Adults with septic shock and extreme hyperferritinemia exhibit pathogenic immune variation.
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DOI：
10.1038/s41435-018-0030-3
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发表时间：
2019-07
影响因子：
5
通讯作者：
Carcillo JA
中科院分区：
文献类型：
--
作者：
Kernan KF;Ghaloul-Gonzalez L;Shakoory B;Kellum JA;Angus DC;Carcillo JA
对白细胞介素1β受体拮抗剂（IL 1 RA）治疗感染性休克的阴性试验进行的事后亚组分析表明，具有巨噬细胞活化综合征（MAS）特征的患者在治疗后死亡率的相对风险降低了50%。在这里，我们寻求这种差异反应的遗传基础。从1341名参加感染性休克早期目标导向治疗的ProCESS试验的患者中，我们选择了6名具有MAS特征和最高铁蛋白的患者进行全外显子组测序（平均值24，030.7 ηg/ml，+/SEM 7，411.1）。鉴定出11种罕见（次要等位基因频率<5%）致病性或可能致病性变异体，可引起家族性噬血细胞性嗜酸性组织细胞增多症、非典型溶血性尿毒症综合征、家族性地中海热和Cryopyrin相关周期性发热等单基因疾病。在这些条件下，目前用IL 1 RA靶向7种鉴定的变体，用抗C5抗体靶向4种。基因靶向精准医学可能会使这一感染性休克和致病性免疫变异患者亚组受益。
Post-hoc subgroup analysis of the negative trial of interleukin-1β receptor antagonist (IL1RA) for septic shock suggested that patients with features of macrophage activation syndrome (MAS) experienced a 50% relative risk reduction for mortality with treatment. Here we seek a genetic basis for this differential response. From 1341 patients enrolled in the ProCESS trial of early goal directed therapy for septic shock, we selected 6 patients with MAS features and the highest ferritin, for whole exome sequencing (mean 24,030.7 ηg/ml, +/SEM 7,411.1). Eleven rare (minor allele frequency <5%) pathogenic or likely pathogenic variants causal for the monogenic disorders of Familial Hemophagocytic Lymphohistiocytosis, atypical Hemolytic Uremic Syndrome, Familial Mediterranean Fever, and Cryopyrin-associated Periodic Fever were identified. In these conditions, seven of the identified variants are currently targeted with IL1RA and four with anti-C5 antibody. Gene-targeted precision medicine may benefit this subgroup of patients with septic shock and pathogenic immune variation.
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影响因子：
--
作者：
Booty, Matthew G.;Chae, Jae Jin;Aksentijevich, Ivona
通讯作者：
Aksentijevich, Ivona
DOI：
10.1016/j.jaci.2015.06.048
发表时间：
2016-01
期刊：
The Journal of allergy and clinical immunology
影响因子：
--
作者：
Cetica V;Sieni E;Pende D;Danesino C;De Fusco C;Locatelli F;Micalizzi C;Putti MC;Biondi A;Fagioli F;Moretta L;Griffiths GM;Luzzatto L;Aricò M
通讯作者：
Aricò M
影响因子：
120.7
作者：
FISHER, CJ;DHAINAUT, JFA;STABLEIN, D
通讯作者：
STABLEIN, D
影响因子：
9.3
作者：
Kyriazopoulou E;Leventogiannis K;Norrby-Teglund A;Dimopoulos G;Pantazi A;Orfanos SE;Rovina N;Tsangaris I;Gkavogianni T;Botsa E;Chassiou E;Kotanidou A;Kontouli C;Chaloulis P;Velissaris D;Savva A;Cullberg JS;Akinosoglou K;Gogos C;Armaganidis A;Giamarellos-Bourboulis EJ;Hellenic Sepsis Study Group
通讯作者：
Hellenic Sepsis Study Group
DOI：
10.4084/mjhid.2015.008
发表时间：
2015-01-01
影响因子：
3.2
作者：
Basheer, Aneesh;Padhi, Somanath;Kanungo, Reba
通讯作者：
Kanungo, Reba