A novel truncating mutation in MYD88 in a patient with BCG adenitis, neutropenia and delayed umbilical cord separation

被引：10

作者：

Platt, Craig D. ^{[1
]}

Zaman, Fatima ^{[1
]}

Wallace, Jacqueline G. ^{[1
]}

Seleman, Michael ^{[1
]}

Chou, Janet ^{[1
]}

Al Sukaiti, Nashat ^{[2
]}

Geha, Raif S. ^{[1
]}

机构：

[1] Harvard Med Sch, Boston Childrens Hosp, Div Immunol, Boston, MA 02115 USA

[2] Royal Hosp, Dept Pediat, Allergy & Clin Immunol Unit, Muscat, Oman

来源：

CLINICAL IMMUNOLOGY | 2019年 / 207卷

关键词：

MyD88; deficiency; BCG; Delayed umbilical cord separation; Neutropenia; CALMETTE-GUERIN; IRAK-4;

D O I：

10.1016/j.clim.2019.07.004

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

Mutations in MYD88 cause susceptibility to invasive bacterial infections through impaired signaling downstream of toll-like receptors (TLRs) and IL-1 receptors. We studied a patient presenting with neutropenia, delayed umbilical cord separation, BCG adenitis, andP. aeruginosapneumonia. Next-generation DNA sequencing identified a novel homozygous truncation mutation in MYD88 that abolishes MYD88 expression. The patient's dermal fibroblasts had severely impaired IL-6 production after stimulation with ligands for the MyD88-dependent receptors TLR2, TLR4 and IL-1R, while responses to ligands for the MyD88-independent receptors TLR3 and TNF-alpha were preserved. Notably, secretion of TNF-alpha, which is essential for BCG control, was also impaired after LPS stimulation. In this first report of BCG infection in MyD88 deficiency, data suggest that MyD88-dependent INF-alpha production contributes to control of mycobacterial disease.

引用

页码：40 / 42

页数：3

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