ABSTRACT
Introduction
With a growing knowledge of Inborn errors immunity (IEI), immunological profiling and genetic predisposition to IEI phenocopies have been developed in recent years.
Areas covered
Here we summarized the correlation between various pathogen invasions, autoantibody profiles, and corresponding clinical features in the context of patients with IEI phenocopies. It has been extensively evident that patients with anti-cytokine autoantibodies underly impaired anti-pathogen immune responses and lead to broad unregulated inflammation and tissue damage. Several hypotheses of anti-cytokine autoantibodies production are summarized here, including a defective negative selection of autoreactive T cells, abnormal germinal center formation, molecular mimicry, HLA class II allele region, lack of auto-reactive lymphocyte apoptosis, and other possible hypotheses.
Expert opinion
Phenocopies of IEI associated with anti-cytokine autoantibodies are increasingly recognized as one of the causes of acquired immunodeficiency and susceptibility to certain pathogen infections, especially facing the current challenge of the COVID-19 pandemic. By investigating clinical, genetic, and pathogenesis autoantibodies profiles associated with various pathogens’ susceptibilities, we could better understand the IEI phenocopies with anti-cytokine autoantibodies, especially for those that underlie life-threatening SARS-CoV-2.
Article highlights
More than 1200 reported IEI phenocopy cases with at least one type of anti-cytokine autoAbs were summarized from the perspectives of genetic, clinical manifestation and pathogen susceptibility.
As an expanding universe, studies of phenocopies of human inborn errors of immunity provided us with forecast pathogenesis, clinical phenotypes, and possible therapy strategy when infectious diseases widely spread. Insight into autoimmune diseases (including APECED, Thymoma, SLE, RA), several main hypotheses illustrated the possible mechanisms of abnormal autoAbs generation.
IEIs patients with impaired cytokines pathway (including IFN-γ, IL-6, IL12, IL17A/F, IL22, Type I IFN, and GM-CSF) due to single genetic defects revealed mechanisms of cytokines in the host defense. Various anti-cytokines autoAbs had been associated with several pathogens, including bacteria, viruses, and fungi.
aAbs-IFN-γ positive patients have a broad infectious spectrum of bacteria (especially on Mycobacteria, Salmonella), viruses (mainly VZV), and fungi. aAbs-IL-6 positive cases present higher severe bacterial infection (mainly Streptococcus spp., Staphylococcus spp.). aAbs-IL17A/F and/or aAbs-IL-22 show higher susceptibility to the virus (mainly VZV, HSV and SARS-CoV-2) and fungi (mainly C. albicans). AutoAbs against type I IFN are the basis of severe viral infection including SARS-CoV-2, VZV, HSV, CMV, IVA, IVB, YFV-17d vaccine.
aAbs-GM-CSF positive individuals associated with higher susceptibility to bacteria (Nocardia spp. and Mycobacteria spp.) and fungi (Candida spp.). Insight of associations of pathogen and autoAbs profiles highlighted susceptibility to infectious risk factors, clinical management, pre-diagnose strategies and prognostic estimation of these patients with IEI phenocopies due to anti-cytokine autoAbs.
Declaration of interest
The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
Reviewer disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.
Supplementary material
Supplemental data for this article can be accessed online at https://doi.org/10.1080/1744666X.2023.2208863.