Chung Sharon A, Shum Anthony K
aRosalind Russell/Ephraim P. Engleman Rheumatology Research CenterbDepartment of Medicine, Division of Pulmonary and Critical Care, , University of California San Francisco, San Francisco, California, USA.
Curr Opin Rheumatol. 2016 Jul;28(4):346-51. doi: 10.1097/BOR.0000000000000298.
We review select studies of newly discovered rare variants in autoimmune diseases with a focus on newly described monogenic disorders, rheumatoid arthritis, and systemic lupus erythematosus.
Two new monogenic syndromes of inflammatory arthritis were discovered using whole exome sequencing: the coatomer subunit alpha syndrome because of rare mutations in coatomer subunit alpha and haploinsufficiency of A20 resulting from rare mutations in TNFAIP3. Targeted exon sequencing identified rare variants in IL2RA and IL2RB associated with rheumatoid arthritis. Rare variants in TREX1 and other genes associated with monogenic interferonopathies are also associated with systemic lupus erythematosus.
Rare genetic variants contribute to the heritability of autoimmunity and provide key insight into both novel and previously implicated immunological pathways that are disrupted in autoimmune diseases.
我们回顾了自身免疫性疾病中新发现的罕见变异的相关研究，重点关注新描述的单基因疾病、类风湿关节炎和系统性红斑狼疮。
通过全外显子组测序发现了两种新的炎症性关节炎单基因综合征：由于衣被蛋白亚基α的罕见突变导致的衣被蛋白亚基α综合征，以及由于TNFAIP3中的罕见突变导致的A20单倍剂量不足。靶向外显子测序确定了与类风湿关节炎相关的IL2RA和IL2RB中的罕见变异。TREX1和其他与单基因干扰素病相关的基因中的罕见变异也与系统性红斑狼疮有关。
罕见基因变异促成了自身免疫性的遗传，并为自身免疫性疾病中被破坏的新的和先前涉及的免疫途径提供了关键见解。
