Maggadottir Solrun M, Sullivan Kathleen E
The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Curr Opin Rheumatol. 2014 Sep;26(5):570-8. doi: 10.1097/BOR.0000000000000091.
Immune deficiency and autoimmunity have been recognized as cotravelers for decades. This clinically oriented review brings together our evolving mechanistic understanding to highlight associations of particular relevance to rheumatologists.
Conceptually, all autoimmunity derives from a loss of tolerance. This distinguishes it from autoinflammation in which the innate immune system is dysregulated without necessarily affecting tolerance. Studies have demonstrated the profound effects of signaling defects, apoptotic pathways and the ramifications of homeostatic proliferation on tolerance. This foundation has translated into an improved understanding of the specific associations of autoimmune diseases with immune deficiencies. This important foundation paves the way for personalized treatment strategies.
This review identifies critical mechanisms important to conceptualize the association of primary immune deficiencies and autoimmunity. It highlights a growing appreciation of the hidden single gene defects affecting T-cells within the group of patients with early-onset pleomorphic autoimmunity.
免疫缺陷和自身免疫被认为是数十年来的“同行者”。这篇以临床为导向的综述汇集了我们不断发展的机制理解，以突出与风湿病学家特别相关的关联。
从概念上讲，所有自身免疫都源于耐受性的丧失。这使其与自身炎症区分开来，在自身炎症中，先天免疫系统失调但不一定影响耐受性。研究已经证明了信号缺陷、凋亡途径以及稳态增殖对耐受性的深远影响。这一基础已转化为对自身免疫性疾病与免疫缺陷之间特定关联的更好理解。这一重要基础为个性化治疗策略铺平了道路。
本综述确定了对于理解原发性免疫缺陷与自身免疫之间关联至关重要的关键机制。它强调了人们越来越认识到在早发性多形性自身免疫患者群体中影响T细胞的隐藏单基因缺陷。
