Severe delayed hypersensitivity reactions to IL-1 and IL-6 inhibitors link to common HLA-DRB1*15 alleles.
Severe delayed hypersensitivity reactions to IL-1 and IL-6 inhibitors link to common HLA-DRB1*15 alleles.
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DOI：
10.1136/annrheumdis-2021-220578
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发表时间：
2022-03
影响因子：
27.4
通讯作者：
Hollenbach, Jill A.
中科院分区：
文献类型：
--
作者：
Saper, Vivian E.;Ombrello, Michael J.;Tremoulet, Adriana H.;Montero-Martin, Gonzalo;Prahalad, Sampath;Canna, Scott;Shimizu, Chisato;Deutsch, Gail;Tan, Serena Y.;Remmers, Elaine F.;Monos, Dimitri;Hahn, Timothy;Phadke, Omkar K.;Cassidy, Elaine;Ferguson, Ian;Mallajosyula, Vamsee;Xu, Jianpeng;Duque, Jaime S. Rosa;Chua, Gilbert T.;Ghosh, Debopam;Szymanski, Ann Marie;Rubin, Danielle;Burns, Jane C.;Tian, Lu;Fernandez-Vina, Marcelo A.;Mellins, Elizabeth D.;Hollenbach, Jill A.
伴有嗜酸性粒细胞增多和全身症状的药物反应 (DRESS) 是一种严重的迟发型超敏反应 (DHR)。我们在一小群患有非典型肺病的斯蒂尔病患者中观察到白细胞介素 1 (IL-1) 或白细胞介素 6 (IL-6) 抑制剂的 DRESS。我们试图将 DRESS 患者与耐药斯蒂尔对照组患者的特征进行比较。我们分析了人类白细胞抗原 (HLA) 等位基因与抑制剂相关 DHR 的关联，包括在一个小型川崎病 (KD) 队列中。在一项病例/对照研究中，我们收集了具有抑制剂相关 DRESS 特征的多中心斯蒂尔患者 (n=66) 和耐药斯蒂尔对照患者 (n=65)。我们回顾性分析了所有 Still 受试者和 HLA 型 94/131 的临床数据。欧洲 Still’s-DRESS 病例与 INCHARGE 儿科 Still’s 病例 (n=550) 进行血统匹配，并比较 HLA 等位基因频率。还使用 Still’s-DRESS 病例 (n=64) 与耐药 Still’s 对照 (n=30) 进行比较，对 HLA 关联进行了分析。 KD 受试者 (n=19) 也进行了类似的研究。 Still’s-DRESS 特征包括嗜酸性粒细胞增多 (89%)、AST-ALT 升高 (75%) 和非消失性皮疹 (95%；88% 涉及面部)。 Still’s-DRESS 组 (64%) 与耐药 Still’s 组 (3%；p=1.9×10−14) 相比，治疗期间巨噬细胞激活综合征很常见。我们发现，与 INCHARGE Still 对照 (p=7.5×10−13) 和自我鉴定、祖先匹配的 Still 对照 (p=6.3×10−10) 相比，Still’s-DRESS 病例中 HLA-DRB1*15 单倍型显着富集。在 KD 队列中，DRB1*15:01 仅存在于疑似阿那白滞素反应的患者中。 DRESS 型反应发生在接受 IL-1/IL-6 抑制剂治疗的患者中，并且与常见的 HLA-DRB1*15 单倍型密切相关。有必要考虑处方前 HLA 分型并对这些药物的严重反应保持警惕。
Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe, delayed hypersensitivity reaction (DHR). We observed DRESS to inhibitors of interleukin 1 (IL-1) or interleukin 6 (IL-6) in a small group of Still’s patients with atypical lung disease. We sought to characterize features of Still’s patients with DRESS compared to drug-tolerant Still’s controls. We analyzed human leukocyte antigen (HLA) alleles for association to inhibitor-related DHR, including in a small Kawasaki disease (KD) cohort. In a case/control study, we collected a multicenter series of Still’s patients with features of inhibitor-related DRESS (n=66) and drug-tolerant Still’s controls (n=65). We retrospectively analyzed clinical data from all Still’s subjects and HLA-typed 94/131. European Still’s-DRESS cases were ancestry-matched to INCHARGE pediatric Still’s cases (n=550) and compared for HLA allele frequencies. HLA association also was analyzed using Still’s-DRESS cases (n=64) compared to drug-tolerant Still’s controls (n=30). KD subjects (n=19) were similarly studied. Still’s-DRESS features included eosinophilia (89%), AST-ALT elevation (75%), and non-evanescent rash (95%; 88% involving face). Macrophage activation syndrome during treatment was frequent in Still’s-DRESS (64%) versus drug-tolerant Still’s (3%; p=1.9×10−14). We found striking enrichment for HLA-DRB1*15 haplotypes in Still’s-DRESS cases versus INCHARGE Still’s controls (p=7.5×10−13) and versus self-identified, ancestry-matched Still’s controls (p=6.3×10−10). In the KD cohort, DRB1*15:01 was present only in those with suspected anakinra reactions. DRESS-type reactions occur among patients treated with IL-1/IL-6 inhibitors and strongly associate with common HLA-DRB1*15 haplotypes. Consideration of pre-prescription HLA typing and vigilance for serious reactions to these drugs are warranted.
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影响因子：
12.7
作者：
Quartuccio, Luca;Sonaglia, Arianna;De Vita, Salvatore
通讯作者：
De Vita, Salvatore
影响因子：
4.4
作者：
Jamilloux, Yvan;Gerfaud-Valentin, Mathieu;Seve, Pascal
通讯作者：
Seve, Pascal
DOI：
10.1186/s12969-015-0047-3
发表时间：
2015-11-20
期刊：
Pediatric rheumatology online journal
影响因子：
--
作者：
Nirmala N;Brachat A;Feist E;Blank N;Specker C;Witt M;Zernicke J;Martini A;Junge G
通讯作者：
Junge G
DOI：
10.1038/nrrheum.2011.68
发表时间：
2011-06-07
期刊：
Nature reviews. Rheumatology
影响因子：
--
作者：
通讯作者：
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影响因子：
12.3
作者：
Matzaraki V;Kumar V;Wijmenga C;Zhernakova A
通讯作者：
Zhernakova A