Human inborn errors of immunity: An expanding universe

Abstract

<jats:p>Molecular, cellular, and clinical studies of human inborn errors of immunity have revolutionized our understanding of their pathogenesis, considerably broadened their spectrum of immunological and clinical phenotypes, and enabled successful targeted therapeutic interventions. These studies have also been of great scientific merit, challenging a number of immunological notions initially established in inbred mice while revealing previously unrecognized mechanisms of host defense by leukocytes and other cells and of both innate and adaptive tolerance to self.</jats:p>

Coronavirus disease 2019 in patients with inborn errors of immunity: An international study

“…First, asymptomatic or mildly symptomatic SARS-CoV-2–infected patients with IEI are likely to be underdiagnosed, mainly due to regional testing priorities contributing to an ascertainment bias of such a retrospective study. Second, because we were guided by the most recent update of IEI, 16 , 17 , 18 it is unlikely that all patients with IEI who have been infected with SARS-CoV-2 were captured by our survey. Indeed, the field of IEI continues to grow rapidly, with more than 35 novel genetic defects having been described since the last update by the International Union of Immunological Societies committee.…”

“…15 This reflects the discoveries of patients with inborn errors of immunity (IEI) who exhibit increased susceptibility to pathogen Abbreviations used AGS: Aicardi-Goutieres syndrome AIHA: Autoimmune hemolytic anemia ALPS: Autoimmune lymphoproliferative syndrome AR: Autosomal-recessive CGD: Chronic granulomatous disease CID: Combined immunodeficiency COVID-19: Coronavirus disease 2019 CVID: Common variable immune deficiency HLH: Hemophagocytic lymphohistiocytosis HSCT: Hematopoietic stem cell transplantation ICU: Intensive care unit IEI: Inborn errors of immunity P: Patient PID: Primary immunodeficiency SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2 X-CGD: X-linked chronic granulomatous disease X-SCID: X-linked severe combined immunodeficiency infection. 16,17 Although more than 430 monogenic IEIs have been described, [16][17][18] the consequences of SARS-CoV-2 infection have been reported for only a few individuals with these conditions. [19][20][21][22] Thus, the aim of this multicenter, retrospective international study was to assess the impact of SARS-CoV-2 infection on patients with IEIs, thereby providing the first comprehensive description on the susceptibility of an at-risk population of patients to SARS-CoV-2 infection, as well as their COVID-19 clinical course, severity, complications, and outcomes.…”

“… 15 This reflects the discoveries of patients with inborn errors of immunity (IEI) who exhibit increased susceptibility to pathogen infection. 16 , 17 Although more than 430 monogenic IEIs have been described, 16 , 17 , 18 the consequences of SARS-CoV-2 infection have been reported for only a few individuals with these conditions. 19 , 20 , 21 , 22 …”

How to evaluate for immunodeficiency in patients with autoimmune cytopenias: laboratory evaluation for the diagnosis of inborn errors of immunity associated with immune dysregulation

“…At the start of the third decade of the 21st century, it is undisputed that genetic evaluation plays a key role in the diagnosis of patients with IEIs, including those with autoimmune phenotypes, and this represents an ever-evolving and expanding area of study. 24,25 Currently, the clinician is confronted with an embarrassment of riches when it comes to genetic testing because there are targeted NGS panels with defined sets of genes, WES, and whole-genome sequencing (WGS). 26,27 Some key rules of thumb can be employed to determine which approach to use and to deploy these in a systematic and tiered manner.…”

Unraveling the Immune Response in Severe COVID-19

“…In human immunology, detailed analyses of individual patients with unique clinical presentation have proven incredibly informative and driven much of the characterization of the ~ 400 primary immunodeficiency disorders known to date [ 12 ]. Bouadma et al report in this issue a careful examination of the immune response in a single patient who succumbed to COVID-19, and this analysis corroborates several of the immune features discussed above from population studies.…”