Autoimmunity and immunodeficiency were previously considered to be mutually exclusive conditions; however, increased understanding of the complex immune regulatory and signalling mechanisms involved, coupled with the application of genetic analysis, is revealing the complex relationships between primary immunodeficiency syndromes and autoimmune diseases. Single-gene defects can cause rare diseases that predominantly present with autoimmune symptoms. Such genetic defects also predispose individuals to recurrent infections (a hallmark of immunodeficiency) and can cause primary immunodeficiencies, which can also lead to immune dysregulation and autoimmunity. Moreover, risk factors for polygenic rheumatic diseases often exist in the same genes as the mutations that give rise to primary immunodeficiency syndromes. In this Review, various primary immunodeficiency syndromes are presented, along with their pathogenetic mechanisms and relationship to autoimmune diseases, in an effort to increase awareness of immunodeficiencies that occur concurrently with autoimmune diseases and to highlight the need to initiate appropriate genetic tests. The growing knowledge of various genetically determined pathologic mechanisms in patients with immunodeficiencies who have autoimmune symptoms opens up new avenues for personalized molecular therapies that could potentially treat immunodeficiency and autoimmunity at the same time, and that could be further explored in the context of autoimmune rheumatic diseases.

自身免疫和免疫缺陷以前被认为是互斥条件；然而，对涉及的复杂免疫调节和信号传导机制的加深了解，再加上基因分析的应用，揭示了原发性免疫缺陷综合症与自身免疫性疾病之间的复杂关系。单基因缺陷会导致罕见疾病，主要表现为自身免疫症状。此类遗传缺陷还使个体易于复发感染（免疫缺陷的标志），并可能导致原发性免疫缺陷，这也可能导致免疫失调和自身免疫。而且，多基因风湿性疾病的危险因素通常与引起原发性免疫缺陷综合症的突变存在于相同的基因中。在这篇评论中，为了提高人们对与自身免疫疾病同时发生的免疫缺陷的认识，并强调启动适当的基因检测的必要性，提出了各种原发性免疫缺陷综合症，以及它们的致病机制和与自身免疫疾病的关系。对具有自身免疫症状的免疫缺陷患者的各种遗传学确定的病理机制的日益了解，为个性化分子疗法开辟了新途径，可以同时治疗免疫缺陷和自身免疫，并且可以在自身免疫性风湿性疾病的背景下进一步探索。努力提高对自身免疫性疾病同时发生的免疫缺陷的认识，并强调需要进行适当的基因检测。对具有自身免疫症状的免疫缺陷患者的各种遗传学确定的病理机制的日益了解，为个性化分子疗法开辟了新途径，可以同时治疗免疫缺陷和自身免疫，并且可以在自身免疫性风湿性疾病的背景下进一步探索。努力提高对自身免疫性疾病同时发生的免疫缺陷的认识，并强调需要进行适当的基因检测。对具有自身免疫症状的免疫缺陷患者的各种遗传学确定的病理机制的日益了解，为个性化分子疗法开辟了新途径，可以同时治疗免疫缺陷和自身免疫，并且可以在自身免疫性风湿性疾病的背景下进一步探索。