A variety of genetic abnormalities have been described during the 1990s, thanks to breakthroughs in molecular biology. The International Union of Immunological Sciences has revised its categorization of genetic abnormalities linked with primary immunological deficiencies, which now total 354. With an ever-expanding list of novel monogenic illnesses and a greater knowledge of the immunobiology and function of these faulty genes, new treatments have developed, many of which are focused specifically at the autoimmune and inflammatory problems that plague these individuals. Immune deficits caused by gain-of-function (GOF) mutations are a possible target for targeted treatments to reduce the muta’s GOF activities in the mutated genes. In addition to their heightened vulnerability to infections, many individuals suffer from autoimmune and inflammatory disorders that are difficult to treat with traditional treatments. The activated phospholipase-3-kinase syndrome, cytotoxic T lymphocyte-associated antigen-4 haploinsufficiency, lipopolysaccharide-responsive beige-like anchor deficiency, and GOF mutations of signal transducer and activator of transcription 1 and 3 immune deficiencies will be discussed. The targeted treatments for each of these immunological inadequacies will be outlined, employing small molecule kinase inhibitors and fusion protein biologic modifiers.
This review looks at recent advancements in precision medicine therapy of various primary immunodeficiency disorders with immunological dysregulation. Understanding the immunobiology of these GOF mutations has resulted in the use of biologic treatments to better regulate the autoimmune and inflammatory symptoms.
