Coppola Emma, Giardino Giuliana, Romano Roberta, Capalbo Donatella, Italiani Paola, Boraschi Diana, De Rosa Antonio, Toriello Elisabetta, Palatucci Annateresa, Rubino Valentina, Ruggiero Giuseppina, Salerno Mariacarolina, Pignata Claudio, Cirillo Emilia
Department of Translational Medical Sciences, Pediatric Section, Federico II University, Naples, Italy.
Institute of Biochemistry and Cell Biology, National Research Council, Naples, Italy.
Front Immunol. 2025 Sep 9;16:1667000. doi: 10.3389/fimmu.2025.1667000. eCollection 2025.
Autoimmune polyglandular syndrome type 1 (APS-1) is a rare inborn error of immunity caused by mutations in the gene, typically associated with chronic mucocutaneous candidiasis, hypoparathyroidism, and adrenal insufficiency. We report the first known case of APS-1 complicated by a life-threatening combination of secondary hemophagocytic lymphohistiocytosis (sHLH) and atypical hemolytic uremic syndrome (aHUS), successfully treated with targeted and supportive therapies.
A 16-year-old female with a diagnosis of APS-1 confirmed by the presence of the nonsense variant c.415C>T (R139X) in exon 3 and the Finnish major mutation c.769C>T (R257X) in exon 6 of the AIRE gene presented with fever, cytopenias, organomegaly, and hyperferritinemia, fulfilling criteria for sHLH. Despite immunosuppressive therapy, she developed acute kidney injury, thrombocytopenia, and microangiopathic hemolytic anemia, consistent with aHUS. Treatment with the IL - 1 receptor antagonist anakinra and the complement inhibitor eculizumab led to rapid resolution of systemic inflammation and progressive renal and hematological recovery.
sHLH is an exceptionally rare complication in APS-1 and has so far been reported in only one patient with a combined EBV and SARS-CoV-2 infection. aHUS has never been described in patients with APS-1. This case highlights the potential for hyperinflammatory and complement-mediated complications in APS-1, supporting the hypothesis of a cytokine storm syndrome that bridges features of sHLH and aHUS. It broadens the known spectrum of immune dysregulation in APS-1 and underscores the importance of early recognition and combined immunomodulatory treatment in similar clinical scenarios.
1型自身免疫性多腺体综合征（APS-1）是一种罕见的先天性免疫缺陷病，由该基因的突变引起，通常与慢性黏膜皮肤念珠菌病、甲状旁腺功能减退和肾上腺功能不全相关。我们报告了首例已知的APS-1合并危及生命的继发性噬血细胞性淋巴组织细胞增生症（sHLH）和非典型溶血尿毒综合征（aHUS）的病例，通过靶向治疗和支持治疗成功治愈。
一名16岁女性，通过AIRE基因外显子3中无义变体c.415C>T（R139X）和外显子6中芬兰主要突变c.769C>T（R257X）确诊为APS-1，出现发热、血细胞减少、器官肿大和高铁蛋白血症，符合sHLH的标准。尽管进行了免疫抑制治疗，她仍出现急性肾损伤、血小板减少和微血管病性溶血性贫血，符合aHUS。使用白细胞介素-1受体拮抗剂阿那白滞素和补体抑制剂依库珠单抗治疗后，全身炎症迅速消退，肾脏和血液学逐渐恢复。
sHLH是APS-1中极为罕见的并发症，迄今为止仅在一名合并EBV和SARS-CoV-2感染的患者中报道过。aHUS从未在APS-1患者中被描述过。该病例突出了APS-1中存在过度炎症和补体介导并发症的可能性，支持了细胞因子风暴综合征的假说，该假说将sHLH和aHUS的特征联系起来。它拓宽了APS-1中已知的免疫失调谱，并强调了在类似临床情况下早期识别和联合免疫调节治疗的重要性。
