PDF(Pubmed)
Abstract：
Hemophagocytic inflammatory syndrome (HIS) is a rare form of secondary hemophagocytic lymphohistiocytosis caused by an impaired equilibrium between natural killer and cytotoxic T-cell activity, evolving in hypercytokinemia and multiorgan failure. In the context of inborn errors of immunity, HIS occurrence has been reported in severe combined immunodeficiency (SCID) patients, including two cases of adenosine deaminase deficient-SCID (ADA-SCID). Here we describe two additional pediatric cases of ADA-SCID patients who developed HIS. In the first case, HIS was triggered by infectious complications while the patient was on enzyme replacement therapy; the patient was treated with high-dose corticosteroids and intravenous immunoglobulins with HIS remission. However, the patient required HLA-identical sibling donor hematopoietic stem cell transplantation (HSCT) for a definitive cure of ADA-SCID, without HIS relapse up to 13 years after HSCT. The second patient presented HIS 2 years after hematopoietic stem cell gene therapy (GT), secondarily to Varicella-Zoster vaccination and despite CD4+ and CD8+ lymphocytes\' reconstitution in line with other ADA SCID patients treated with GT. The child responded to trilinear immunosuppressive therapy (corticosteroids, Cyclosporine A, Anakinra). We observed the persistence of gene-corrected cells up to 5 years post-GT, without HIS relapse. These new cases of children with HIS, together with those reported in the literature, support the hypothesis that a major dysregulation in the immune system can occur in ADA-SCID patients. Our cases show that early identification of the disease is imperative and that a variable degree of immunosuppression could be an effective treatment while allogeneic HSCT is required only in cases of refractoriness. A deeper knowledge of immunologic patterns contributing to HIS pathogenesis in ADA-SCID patients is desirable, to identify new targeted treatments and ensure patients\' long-term recovery.
摘要：
噬血细胞炎症综合征（HIS）是一种罕见的继发性噬血细胞淋巴组织细胞增多症，由自然杀伤和细胞毒性T细胞活性之间的平衡受损引起，高细胞因子血症和多器官衰竭的演变。在天生的豁免错误的背景下，据报道，严重的联合免疫缺陷（SCID）患者发生了HIS，包括2例腺苷脱氨酶缺陷型SCID(ADA-SCID)。在这里，我们描述了另外两例发展为HIS的ADA-SCID患者的儿科病例。在第一种情况下,在患者接受酶替代疗法时，感染并发症引发了HIS；患者接受大剂量皮质类固醇和静脉免疫球蛋白治疗，HIS缓解。然而,患者需要HLA相同的同胞供者造血干细胞移植（HSCT）以最终治愈ADA-SCID，HSCT后13年无复发。第二位患者在造血干细胞基因治疗（GT）2年后出现HIS，其次是水痘-带状疱疹疫苗接种，尽管CD4+和CD8+淋巴细胞重建与其他接受GT治疗的ADASCID患者一致。孩子对三线性免疫抑制疗法有反应（皮质类固醇，环孢素A,Anakinra).我们观察到基因校正细胞在GT后5年内的持久性，没有复发。这些带着他的孩子的新病例，加上文献中报道的，支持ADA-SCID患者可能发生免疫系统严重失调的假设。我们的病例表明，必须早期识别该疾病，并且不同程度的免疫抑制可能是有效的治疗方法，而仅在难治性病例中需要同种异体HSCT。需要对ADA-SCID患者中有助于HIS发病机理的免疫学模式有更深入的了解，确定新的靶向治疗方法并确保患者长期康复。
