Cellular mechanisms and clinical applications for phenocopies of inborn errors of immunity: infectious susceptibility due to cytokine autoantibodies.

INTRODUCTION: With a growing knowledge of Inborn error 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 were 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.