Novel Discoveries in Immune Dysregulation in Inborn Errors of Immunity

Abstract

With the expansion of our knowledge on inborn errors of immunity (IEI), it gradually becomes clear that immune dysregulation plays an important part. In some cases, autoimmunity, hyperinflammation and lymphoproliferation are far more serious than infections. Thus, immune dysregulation has become significant in disease monitoring and treatment. In recent years, the wide application of whole-exome sequencing/whole-genome sequencing has tremendously promoted the discovery and further studies of new IEI. The number of discovered IEI is growing rapidly, followed by numerous studies of their pathogenesis and therapy. In this review, we focus on novel discovered primary immune dysregulation diseases, including deficiency of SLC7A7, CD122, DEF6, FERMT1, TGFB1, RIPK1, CD137, TET2 and SOCS1. We discuss their genetic mutation, symptoms and current therapeutic methods, and point out the gaps in this field.

Diagnostic Challenges in Patients with Inborn Errors of Immunity with Different Manifestations of Immune Dysregulation

“…Over the years, the wide application of whole-exome sequencing/whole-genome sequencing has significantly promoted the discovery and further study of new IEI and its number has doubled from 2009 to 2019 [ 1 , 140 ]. It is worth mentioning that the number of cases for any particular IEI is usually few, and because of that, a large-scale study of IEI can hardly be conducted [ 140 ]. Furthermore, there are several difficulties in identifying IEI connected with immune dysregulation.…”

“…There are still countries where genetic tests are not widespread and freely available, mostly because of their costs. Moreover, in some patients more than one mutation is present, which makes it even more difficult to find [ 140 , 141 ]. In addition, phenotypes of the same mutation vary between patients, ranging from mild or uncharacteristic symptoms to even life-threatening manifestations [ 140 , 142 , 143 ].…”

“…Moreover, in some patients more than one mutation is present, which makes it even more difficult to find [ 140 , 141 ]. In addition, phenotypes of the same mutation vary between patients, ranging from mild or uncharacteristic symptoms to even life-threatening manifestations [ 140 , 142 , 143 ]. In conclusion, patients with immune dysregulation should be examined scrupulously, and genetic diagnostics should be conducted in cases when it is necessary and possible [ 140 ].…”

“…In addition, phenotypes of the same mutation vary between patients, ranging from mild or uncharacteristic symptoms to even life-threatening manifestations [ 140 , 142 , 143 ]. In conclusion, patients with immune dysregulation should be examined scrupulously, and genetic diagnostics should be conducted in cases when it is necessary and possible [ 140 ]. Early and proper diagnosis seems crucial when we consider IEI patients.…”

Understanding inborn errors of immunity: A lens into the pathophysiology of monogenic inflammatory bowel disease

“…In some, colitis is managed with anti-inflammatory agents ( 16 ), others respond to immune modulators ( 25 ), while others require colectomy ( 23 ). Potential therapeutic avenues include gene therapy or protein replacement ( 26 ).…”