Sponzilli Ivonne, Notarangelo Luigi D
Division of Immunology, Children's Hospital, Harvard Medical School, Boston, MA, USA.
Acta Biomed. 2011 Apr;82(1):5-13.
Primary immune deficiency diseases (PID) comprise a genetically heterogeneous group of disorders that affect distinct components of the innate and adaptive immune system, such as neutrophils, macrophages, dendritic cells, complement proteins, natural killer cells, as well as T and B lymphocytes. Severe combined immunodeficiency (SCID) is a group of disorders characterized by increased susceptibility to severe infections and early death. The diagnosis of SCID is supported by the demonstration of low absolute lymphocyte count and T cell lymphopenia (variably associated with numerical defects of B and NK cells). In the last two decades, advances in the characterization of the molecular pathophysiology of SCID, have permitted the development of novel diagnostic assays based on analysis of the expression of the disease-associated proteins and mutation analysis. More recently, pilot newborn screening programs for the identification of infants with SCID have been initiated in the United States. Prompt and aggressive treatment of infections, antimicrobial prophylaxis (in particular against Pneumocystis jiroveci) and regular administration of immunoglobulins are essential to reduce the risk of early death. However, survival ultimately depends on reconstitution of immune function, that is usually achieved by means of hematopoietic cell transplantation (HCT). Gene therapy and enzyme replacement therapy have also been used successfully is selected forms of SCID. Here we review the molecular and cellular pathophysiology and the mainstay of treatment of SCID.
原发性免疫缺陷病（PID）是一组基因异质性疾病，影响先天性和适应性免疫系统的不同组成部分，如中性粒细胞、巨噬细胞、树突状细胞、补体蛋白、自然杀伤细胞以及T和B淋巴细胞。严重联合免疫缺陷病（SCID）是一组以易患严重感染和早期死亡为特征的疾病。SCID的诊断依据是绝对淋巴细胞计数低和T细胞淋巴细胞减少（可伴有B细胞和NK细胞数量缺陷）。在过去二十年中，SCID分子病理生理学特征的进展使得基于疾病相关蛋白表达分析和突变分析的新型诊断检测得以发展。最近，美国已启动了用于识别SCID婴儿的试点新生儿筛查项目。及时积极地治疗感染、进行抗菌预防（特别是针对耶氏肺孢子菌）以及定期给予免疫球蛋白对于降低早期死亡风险至关重要。然而，生存最终取决于免疫功能的重建，这通常通过造血细胞移植（HCT）来实现。基因治疗和酶替代疗法也已成功用于某些类型的SCID。在此，我们综述SCID的分子和细胞病理生理学以及主要治疗方法。
