Compound Heterozygous Mutations of IL12RB1 in a Patient with Selective Defects in Th17 Differentiation
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LETTER TO EDITOR
Compound Heterozygous Mutations of IL12RB1 in a Patient with Selective Defects in Th17 Differentiation Ming Liu 1,2 & Bingtai Lu 1,2 & Ping Zeng 1 & Bing Huang 1,2 & Yanhui Xu 1,2 & Hanquan Liang 1 & Diyuan Yang 1 & Sida Yang 1 & Hai-bin Luo 3 & Andrew M. Lew 4 & Seth L. Masters 4 & Lanlan Geng 1 & Huasong Zeng 1 & Yuxia Zhang 1,2,5 Received: 14 June 2019 / Accepted: 9 March 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
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 cm2 and 0.3 × 0.3 cm2) 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
Ming Liu, Bingtai Lu and Ping Zeng contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10875-020-00771-0) contains supplementary material, which is available to authorized users. * Lanlan Geng
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