Department of Immunology, Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia; Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom.
Department of Immunology, Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia.
J Allergy Clin Immunol. 2021 Jul;148(1):250-255.e1. doi: 10.1016/j.jaci.2020.11.043. Epub 2020 Dec 15.
Proline-serine-threonine phosphatase-interacting protein 1-associated myeloid-related proteinemia inflammatory (PAMI) syndrome is a novel genetic disorder, causing hypercalprotectinemia and hyperzincemia with inflammatory complications accompanied by cytopenia. Immunosuppressive and/or anticytokine therapy is of limited effect.
Because of cytokine production in nonhematopoietic tissues, the potential therapeutic effect of allogeneic hematopoietic stem cell transplantation (HSCT) in autoinflammatory disorders, including PAMI syndrome, has remained uncertain.
Five patients with PAMI syndrome underwent allogeneic HSCT with myeloablative (4) or reduced-intensity (1) conditioning regimens. Lack of PAMI disease control served as indication for the HSCT in 4 patients and myelodysplastic syndrome development in 1.
All 5 patients engrafted; however, 1 patient at day +13 developed hemophagocytic syndrome, followed by graft rejection at day +17. After 5.5 months, a second HSCT was performed from an alternative donor. A further patient at day +116 developed an intense inflammatory syndrome with significant serositis and severe mitral and aortic valve regurgitation, controlled with adalimumab, tacrolimus, and prednisone. No other noninfectious inflammatory episodes, or acute or chronic graft-versus-host disease, occurred in any patient. At the last follow-up (median, 2.2 years), all 5 patients have predominantly or complete donor chimerism and adequate immune recovery and are free of any PAMI symptoms.
Allogeneic HSCT seems to be an effective option to cure cytopenia and severe autoinflammation in PAMI syndrome and may be a curative option for other proline-serine-threonine phosphatase-interacting protein 1-associated inflammatory disorders with poor therapeutic control.
脯氨酰-丝氨酰-苏氨酰磷酸酶相互作用蛋白 1 相关髓系相关蛋白血症炎症（PAMI）综合征是一种新型的遗传疾病，导致高钙保护素血症和高锌血症伴炎症并发症，并伴有细胞减少症。免疫抑制和/或抗细胞因子治疗效果有限。
由于非造血组织中细胞因子的产生，同种异体造血干细胞移植（HSCT）在包括 PAMI 综合征在内的自身炎症性疾病中的潜在治疗效果一直存在不确定性。
5 例 PAMI 综合征患者接受了清髓性（4 例）或减低强度（1 例）预处理方案的同种异体 HSCT。4 例患者因缺乏 PAMI 疾病控制，1 例因骨髓增生异常综合征发展而进行 HSCT。
所有 5 例患者均植入，但 1 例在+13 天出现噬血细胞综合征，随后在+17 天出现移植物排斥。5.5 个月后，从另一个供体进行了第二次 HSCT。进一步的患者在+116 天出现强烈的炎症综合征，伴有明显的浆膜炎和严重的二尖瓣和主动脉瓣反流，用阿达木单抗、他克莫司和泼尼松控制。在任何患者中均未发生其他非感染性炎症发作或急性或慢性移植物抗宿主病。在最后一次随访（中位数 2.2 年）时，所有 5 例患者均主要或完全具有供体嵌合性，并且具有足够的免疫恢复，且无任何 PAMI 症状。
同种异体 HSCT 似乎是治疗 PAMI 综合征细胞减少症和严重自身炎症的有效选择，并且可能是其他治疗控制不佳的脯氨酰-丝氨酰-苏氨酰磷酸酶相互作用蛋白 1 相关炎症性疾病的治愈选择。
