Activated phosphoinositide 3-kinase δ syndrome 1 (APDS1) is a primary immunodeficiency disease caused by gain-of-function mutations in PIK3CD. Clinical features of autoimmune disease have been reported in patients with APDS1. In this study, we reported three patients with APDS1 presenting with systemic lupus erythematosus (SLE) phenotype. The clinical manifestations included recurrent respiratory tract infection, lymphoproliferation, Coombs-positive hemolytic anemia, decreased complement fractions, positive antinuclear antibodies, renal complications related to SLE associated diseases, which met the clinical spectrum of APDS1 and the classification criteria of SLE. The immunological phenotype included an inversion in the CD4:CD8 ratio, an increase in both non-circulating Tfh CD4⁺ memory T and circulating Tfh populations, a low level of recent thymic emigrant T cells, overexpression of CD57 on T cells, and a decrease in B cells with fewer antibody class switch recombination. These phenotypes detected in patients with APDS1 presenting with SLE were resemble that in patients with APDS1 presenting without SLE. Meanwhile, we described the effect of glucocorticoids and rapamycin therapy on patients with APDS1. The phosphorylation of S6 at Ser235/236 was inhibited in patients with APDS1 who underwent glucocorticoids therapy, including two who presented with SLE phenotype. The phosphorylation of AKT at Ser473 and phosphorylation of S6 at Ser235/236 were inhibited in other patients with APDS1 who underwent rapamycin therapy. Here, we showed the coexistence of immunodeficiency and SLE phenotype in APDS1, and the inhibition of rapamycin in activated Akt-mTOR signaling pathway.

活化的磷酸肌醇 3-激酶 δ 综合征 1 (APDS1) 是一种由PIK3CD功能获得性突变引起的原发性免疫缺陷疾病。已经在 APDS1 患者中报告了自身免疫性疾病的临床特征。在这项研究中，我们报告了三名出现系统性红斑狼疮 (SLE) 表型的 APDS1 患者。临床表现包括反复呼吸道感染、淋巴细胞增生、Coombs阳性溶血性贫血、补体分数降低、抗核抗体阳性、SLE相关疾病相关肾脏并发症，符合APDS1的临床谱和SLE的分类标准。免疫表型包括 CD4:CD8 比率的倒置，非循环 Tfh CD4 ⁺记忆 T 和循环 Tfh 群体、近期胸腺移出 T 细胞水平低、T 细胞上 CD57 的过度表达以及 B 细胞减少，抗体类别转换重组较少。在出现 SLE 的 APDS1 患者中检测到的这些表型与在没有 SLE 的 APDS1 患者中检测到的表型相似。同时，我们描述了糖皮质激素和雷帕霉素治疗对 APDS1 患者的影响。在接受糖皮质激素治疗的 APDS1 患者中，S6 在 Ser235/236 处的磷酸化受到抑制，其中包括两名出现 SLE 表型的患者。在其他接受雷帕霉素治疗的 APDS1 患者中，AKT 在 Ser473 处的磷酸化和 S6 在 Ser235/236 处的磷酸化受到抑制。在这里，我们展示了 APDS1 中免疫缺陷和 SLE 表型的共存，