Primary immunodeficiencies

Primary immunodeficiencies are failures of the immune system that are written into the genes. Today they are called inborn errors of immunity, and the name is precise: the problem is a pathogenic genetic variant, a change in the DNA capable of causing disease, and it affects how some piece of the body's defense develops or how it works. It is not a defense worn down by something that happened later: it is a piece of the defense that never finished being built.

They are inherited in several ways. One altered copy of the gene may be enough, which is autosomal dominant inheritance; both copies may be needed, which is recessive inheritance; the gene may sit on the X chromosome, and then it is called X-linked inheritance; and there are more complex inheritance patterns. These are not a handful of diseases: nearly five hundred distinct genetic defects are known.

It is worth telling them apart from the secondary immunodeficiencies, which are not inherited but acquired, when something damages an immune system that was normal at birth. And although the first thing that comes to mind is infections that return again and again, these diseases also show up as autoimmunity, when the defense attacks the person's own body, as allergy, as inflammation and as malignancies.