Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics (Capital Medical University), Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, No. 56 Nanlishi Road, Beijing, China.
Hematologic Disease Laboratory, Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Discipline of Pediatrics (Capital Medical University), Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.
Int J Immunopathol Pharmacol. 2021 Jan-Dec;35:20587384211025934. doi: 10.1177/20587384211025934.
Autoimmune lymphoproliferative syndrome (ALPS) usually presents in childhood with fever, nonmalignant splenomegaly, and lymphadenopathy along with cytopenia, which is caused by mutations in the FAS apoptotic pathway. The TCRαβ + CD4/CD8 double-negative T cells (DNT), one of required criteria of ALPS, will rise markedly in ALPS. Human Protein kinase C delta (PRKCD) deficiency (OMIM # 615559) was recently identified to be causative for an ALPS-type III with significant B-cell proliferation particularly of immature B cells. We report a pedigree homozygous variation of PRKCD gene (c.36T>G, p. Y12X) which presented with refractory cytopenia, splenomegaly, and polarization of DNT/regulatory T cells (Treg) axis. After repeated recurrence, the patient was treated with mTOR inhibitor sirolimus, which had a safety mechanism and specifically rebalance the DNT/Treg axis. The patient's hemoglobin and clinical condition improved gradually by the application of sirolimus (1.5 mg/m, actual blood concentration 4.27-10.3 ng/l). Homozygous variation in PRKCD may lead to typical ALPS clinical manifestations. Targeting DNT/Treg axis, use of sirolimus in such patients may help to achieve good clinical control.
自身免疫性淋巴组织增生综合征（ALPS）通常在儿童时期出现，表现为发热、非恶性脾肿大和淋巴结病，同时伴有血细胞减少症，这是由 FAS 凋亡途径的突变引起的。T 细胞受体αβ+CD4/CD8 双阴性 T 细胞（DNT）是 ALPS 的必需标准之一，在 ALPS 中会明显升高。人类蛋白激酶 C 德尔塔（PRKCD）缺乏症（OMIM#615559）最近被确定为 III 型 ALPS 的病因，其特征是 B 细胞增殖显著，特别是不成熟 B 细胞。我们报告了一个 PRKCD 基因（c.36T>G，p.Y12X）纯合变异的家系，该变异表现为难治性血细胞减少症、脾肿大和 DNT/调节性 T 细胞（Treg）轴的极化。在反复复发后，患者接受了 mTOR 抑制剂西罗莫司治疗，该药物具有安全机制，并能特异性地重新平衡 DNT/Treg 轴。通过应用西罗莫司（1.5mg/m，实际血药浓度 4.27-10.3ng/l），患者的血红蛋白和临床状况逐渐改善。PRKCD 的纯合变异可能导致典型的 ALPS 临床表现。针对 DNT/Treg 轴，此类患者使用西罗莫司可能有助于实现良好的临床控制。
