Casanova Jean-Laurent, Fieschi Claire, Bustamante Jacinta, Reichenbach Janine, Remus Natasha, von Bernuth Horst, Picard Capucine
Laboratoire de Génétique Humaine des Maladies Infectieuses, Université de Paris René Descartes-INSERM U550, Faculté de Médecine Necker, Paris, France.
J Allergy Clin Immunol. 2005 Aug;116(2):426-30. doi: 10.1016/j.jaci.2005.03.053.
Primary immunodeficiencies are typically seen as rare monogenic conditions associated with detectable immunologic abnormalities, resulting in a broad susceptibility to multiple and recurrent infections caused by weakly pathogenic and more virulent microorganisms. By opposition to these conventional primary immunodeficiencies, we describe nonconventional primary immunodeficiencies as Mendelian conditions manifesting in otherwise healthy patients as a narrow susceptibility to infections, recurrent or otherwise, caused by weakly pathogenic or more virulent microbes. Conventional primary immunodeficiencies are suspected on the basis of a rare, striking, clinical phenotype and are defined on the basis of an overt immunologic phenotype, often leading to identification of the disease-causing gene. Nonconventional primary immunodeficiencies are defined on the basis of a more common and less marked clinical phenotype, which remains isolated until molecular cloning of the causal gene reveals a hitherto undetected immunologic phenotype. Similar concepts can be applied to primary immunodeficiencies presenting other clinical features, such as allergy and autoimmunity. Nonconventional primary immunodeficiencies thus expand the clinical boundaries of this group of inherited disorders considerably, suggesting that Mendelian primary immunodeficiencies are more common in the general population than previously thought and might affect children with a single infectious, allergic, or autoimmune disease.
原发性免疫缺陷通常被视为与可检测到的免疫异常相关的罕见单基因疾病，会导致对致病性较弱和毒性更强的微生物引起的多种反复感染具有广泛易感性。与这些传统的原发性免疫缺陷相反，我们将非常规原发性免疫缺陷描述为孟德尔疾病，在其他方面健康的患者中表现为对致病性较弱或毒性更强的微生物引起的反复或其他感染具有狭窄的易感性。传统的原发性免疫缺陷基于罕见、显著的临床表型而被怀疑，并基于明显的免疫表型来定义，这通常会导致致病基因的鉴定。非常规原发性免疫缺陷基于更常见且不太明显的临床表型来定义，在致病基因的分子克隆揭示出迄今未检测到的免疫表型之前，该表型一直未被发现。类似的概念也可应用于呈现其他临床特征（如过敏和自身免疫）的原发性免疫缺陷。因此，非常规原发性免疫缺陷极大地扩展了这组遗传性疾病的临床边界，表明孟德尔原发性免疫缺陷在普通人群中比以前认为的更为常见，并且可能影响患有单一感染性、过敏性或自身免疫性疾病的儿童。
