Compound Heterozygous Mutations of IL12RB1 in a Patient with Selective Defects in Th17 Differentiation
Compound Heterozygous Mutations of IL12RB1 in a Patient with Selective Defects in Th17 Differentiation
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Th17 分化选择性缺陷患者 IL12RB1 复合杂合突变
DOI：
10.1007/s10875-020-00771-0
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发表时间：
2020
影响因子：
9.1
通讯作者：
Zhang Yuxia
中科院分区：
文献类型：
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作者：
Liu Ming;Lu Bingtai;Zeng Ping;Huang Bing;Xu Yanhui;Liang Hanquan;Yang Diyuan;Yang Sida;Luo Hai-bin;Lew Andrew M.;Masters Seth L.;Geng Lanlan;Zeng Huasong;Zhang Yuxia
致编辑：白细胞介素 12 受体亚基 β1 (IL12RB1) 的突变会损害 IL-12 和 IL-23 介导的 T 辅助细胞 1 (Th1) 和/或 Th17 分化，并导致孟德尔对分枝杆菌疾病的易感性 [1]。迄今为止，据报道只有一名患者存在与致命结果相关的体液免疫缺陷。在此，我们报道另一例IL12RB1复合杂合变异的病例，该病例表现出IL12RB1表达降低、B细胞缺乏、神经病变、严重皮肤和软组织炎症和坏死、反复感染和腹泻，并在长期糖皮质激素治疗和脓毒症后去世。我们调查了一名非近亲中国父母所生的 1 岁 7 个月大的女孩。该患者在发烧和肺炎治疗后首次入院神经内科，表现出不愿行走、四肢颤抖和语言能力受损。考虑感染后自身免疫性神经病变，因此给予静脉注射糖皮质激素和免疫球蛋白。因全身皮肤软组织严重炎症坏死、持续性腹泻、反复发热、神经体征无改善，被转入免疫科和重症监护室（图1a-c）。皮质类固醇治疗持续到第40天，此时皮肤坏死最严重，并且在她的血培养中检测到多种细菌和真菌病原体（肺炎克雷伯菌、溶血性葡萄球菌和近平滑念珠菌）。她的感染接受了多种抗生素（头孢哌酮钠和舒巴坦钠、亚胺培南和西司他丁钠、哌拉西林钠和舒巴坦钠、庆大霉素）和抗真菌剂（氟康唑）治疗（图1c）。第58天，肢体震颤和皮肤坏死症状得到有效改善，但腹泻和发烧持续存在。第 84 天的结肠镜检查显示直肠有两个溃疡（1 × 1 cm 和 0.3 × 0.3 cm）（图 1b）。孩子在第 120 天时因呼吸和心脏骤停去世（图 1c）。免疫学检查显示住院期间多次血液中性粒细胞和单核细胞增加。相反，自入院以来，血液 B 细胞计数持续较低（图 1d 和补充表 1）。回顾性
To the Editor: Mutations in interleukin 12 receptor subunit β1 (IL12RB1) impair IL-12 and IL-23-mediated T helper 1 (Th1) and/or Th17 differentiation and cause Mendelian susceptibility to mycobacterial diseases [1]. To date, only one patient was reported to have a defect in humoral immunity associated with fatal outcome. Here we report another case with compound heterozygous variations in IL12RB1, who showed decreased IL12RB1 expression, B cell deficiency, neuropathy, severe skin and soft tissue inflammation and necrosis, recurrent infections, and diarrhea, and passed away following prolonged glucocorticoid treatment and sepsis. We investigated a 1 year 7-month old girl born to nonconsanguineous Chinese parents. The patient was first admitted to the neurology department showing unwillingness to walk, limb tremors, and impaired language skills following fever and pneumonia treatment. Post-infection autoimmune neuropathy was considered and accordingly, intravenous glucocorticoids and immunoglobulins were given. She was subsequently transferred to the immunology department and Intensive Care Unit due to severe skin and soft tissue inflammation and necrosis over her whole-body area, persistent diarrhea, recurrent episodes of fever, and lack of improvement of neurological signs (Fig. 1a–c). Corticosteroid treatment was continued until day 40, at which time the skin necrosis was at its worst, and multiple bacterial and fungal pathogens were detected in her blood cultures (Klebsiella pneumoniae, Hemolytic staphylococcus, and Candida parapsilosis). Her infections were treated with multiple antibiotics (cefoperazone sodium and sulbactam sodium, imipenem and cilastatin sodium, piperacillin sodium and sulbactam sodium, gentamicin) and an anti-fungal agent (fluconazole) (Fig. 1c). Signs for limb tremor and skin necrosis were effectively improved by day 58, but the diarrhea and fever persisted. Colonoscopy at day 84 revealed two ulcers (1 × 1 cm and 0.3 × 0.3 cm) in the rectum (Fig. 1b). The child passed away at day 120 due to respiratory and cardiac arrest (Fig. 1c). Immunology workup showed increased blood neutrophils and monocytes on multiple occasions during hospitalization. In contrast, blood B cell counts were persistently low since admitted (Fig. 1d and Supplementary Table 1). Retrospective