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/m², 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) 通常在儿童期出现发热、非恶性脾肿大、淋巴结肿大和血细胞减少，这是由 FAS 凋亡通路突变引起的。TCRαβ+CD4/CD8双阴性T细胞（DNT）是ALPS的必备标准之一，在ALPS中会显着升高。人类蛋白激酶 C δ (PRKCD) 缺乏症 (OMIM # 615559) 最近被确定为具有显着 B 细胞增殖的 III 型 ALPS 的病因，尤其是未成熟 B 细胞。我们报告了 PRKCD 基因 (c.36T>G, p. Y12X) 的谱系纯合变异，表现为难治性血细胞减少、脾肿大和 DNT/调节性 T 细胞 (Treg) 轴的极化。反复复发后，患者接受mTOR抑制剂西罗莫司治疗，它有一个安全机制，专门重新平衡 DNT/Treg 轴。应用西罗莫司（1.5 mg/m² , 实际血浓度 4.27–10.3 ng/l)。PRKCD的纯合变异可能导致典型的ALPS临床表现。针对 DNT/Treg 轴，在此类患者中使用西罗莫司可能有助于实现良好的临床控制。