Six steps in the study of monogenic and autoimmune infectionsa
| Year . | Category . | Condition . | References . |
|---|---|---|---|
| 1985 | Primary immunodeficiencies | ADA deficiency | (85) |
| 1996 | Rare Mendelian infectionsb | MSMD | (24, 25) |
| 2004 | Rare autoimmune phenocopiesc | Type II IFN auto-Abs | (26, 27) |
| 2007 | Rare monogenic infectionsb | HSE | (28, 29) |
| 2018 | Common monogenic infectionsb | Tuberculosis | (30, 31, 86) |
| 2020 | Common autoimmune phenocopiesc | Type I IFN auto-Abs | (33, 34) |
| Year . | Category . | Condition . | References . |
|---|---|---|---|
| 1985 | Primary immunodeficiencies | ADA deficiency | (85) |
| 1996 | Rare Mendelian infectionsb | MSMD | (24, 25) |
| 2004 | Rare autoimmune phenocopiesc | Type II IFN auto-Abs | (26, 27) |
| 2007 | Rare monogenic infectionsb | HSE | (28, 29) |
| 2018 | Common monogenic infectionsb | Tuberculosis | (30, 31, 86) |
| 2020 | Common autoimmune phenocopiesc | Type I IFN auto-Abs | (33, 34) |
Monogenic disorders of complement underlying specific infections (e.g., deficits of the membrane attack complex) are not included, even though they were characterized before 1985, as their molecular genetic etiology was not deciphered until after 1996 (see text and Fig. 3).
Mendelian infections are defined as monogenic infections with complete penetrance, whereas monogenic infections are defined here as displaying incomplete penetrance. While UNC93B1 deficiency was published in 2006, as the first genetic etiology of HSE, incomplete penetrance was only documented in 2007, with the report of TLR3 deficiency.
Autoimmune phenocopies refer to autoantibodies neutralizing cytokines that underlie the same infection as inborn errors of the corresponding cytokine or its receptor. As they can be caused by monogenic disorders of tolerance to self, they cannot rigorously be considered phenocopies (see text and Fig. 6).