Inborn errors of immunity (IEI)

Introduction

What are inborn errors of immunity? 

Recently, the terminology ‘IEI’ appeared in the literature: “to capture the broad range of phenotypes associated with these [PID] disorders, the term ‘inborn errors of immunity’ (IEI) has been proposed."¹

The ‘International Union of Immunological Societies’ (IUIS) expert committee has published genotypic and phenotypical classification of IEI.^2,3 They have curated over 400 disorders, based on 430 genetic single-gene defects and classified them into 10 tables. Each of these tables include 36 to 64 disorders, with a year-on-year increase.

•  Table I - Immunodeficiencies affecting cellular and humoral immunity
•  Table II - Combined immunodeficiencies with associated or syndromic features
•  Table III - Predominantly antibody deficiencies
•  Table IV - Diseases of immune dysregulation
•  Table V - Congenital defects of phagocyte (number or function)
•  Table VI - Defects in intrinsic and innate immunity
•  Table VII - Autoinflammatory diseases
•  Table VIII - Complement deficiencies
•  Table IX - Bone marrow failure
•  Table X - Phenocopies of inborn errors of immunity

The terms IEI and PID are often used interchangeably in the literature. Currently, the term PID is still preferred to IEI.⁴ Although there is an argument for changing the name from PID to IEI, or using these terms interchangeably, there are several caveats, as three of the most common PIDs (which comprise the majority of patients with PID) do not currently have a defined genetic basis (IgA deficiency, common variable immunodeficiency and transient hypogammaglobulinemia of infancy). Even within well-defined phenotypes such as agammaglobulinemia or severe combined immunodeficiency (SCID), not all patients have a genetic explanation for their disorder.