Table 1.
Inborn errors of cytokines or their receptors, their corresponding autoimmune phenocopies (anti-cytokine auto-Abs), and monoclonal antibodies used in therapeutics, together with the associated infectious phenotypes
| Cytokine | Receptor of cytokine | Inborn error of immunity | Main infectious disease | Phenocopies (auto-Abs) | Infectious disease | Therapeutic with monoclonal Abs | Infectious disease |
|---|---|---|---|---|---|---|---|
| Type II IFN (IFN-γ) | IFN-γR1 IFN-γR2 |
IFNG IFNG-R1 IFNGR2 |
- Disseminated M. bovis–BCG disease - Disseminated environmental mycobacteria disease |
Auto-Abs to IFN-γ | - Disseminated environmental mycobacteria disease - Disseminated tuberculosis - Salmonellosis |
- Emapalumab - Fontolizumab - AMG811 |
- Disseminated histoplasmosis - Disseminated salmonellosis |
| Type I IFNs (IFN-α/β) | IFNAR1 IFNAR2 |
IFNAR1
IFNAR2 |
- Herpes virus encephalitis - Severe influenza - Yellow fever - Life-threatening COVID-19 pneumonia |
Auto-Abs to IFN-α2, other IFN-α, IFN-β, IFN-ω | - Life-threatening COVID-19 pneumonia - Yellow fever vaccine disease |
- Sifalimumab/MEDI545 - Rontalizumab/RG-7415 - AGS-009 - S95021/19D11 -Anifrolimab/MEDI-546 |
- Respiratory tract infections - Herpes zoster |
| IL-17A IL-17F |
IL-17RA IL-17RC |
IL17F
IL17RA IL17RC |
Chronic mucocutaneous candidiasis | Auto-Abs to IL-17A, IL-17F | - Chronic mucocutaneous candidiasis | - Secukinumab/AIN457 - Ixekizumab/LY2439821 - Brodalumab/AMG 827 - Bimekizumab |
- Chronic mucocutaneous candidiasis |
| IL-6 | IL-6R GP130/IL6ST |
IL6R
IL6ST |
Staphylococcal cutaneous infections | Auto-Abs to IL-6 | - Staphylococcal cutaneous infections | - Tocilizumab - Sarilumab - Satralizumab - Sirukumab - Siltuximab |
- Staphylococcal cellulitis - Pneumonia by S. aureus |
| GM-CSFa | CSF2RA CSF2RB |
CSF2RA
CSF2RB |
- Nocardiosis? - Cryptococcosis? |
Auto-Abs to GM-CSF | - Pulmonary and extra-pulmonary cryptococcosis - Pulmonary and extra-pulmonary nocardiosis |
- Lenzilumab - Namilumab - Gimsilumab - Otilimab - Mavrilimumab |
- Nasopharyngitis without microbe isolation |
a
As explained in the text, inborn errors of and auto-Abs to GM-CSF underlie PAP. The infectious diseases seen in these patients are relatively diverse and may result from PAP (including its therapy) and/or from impaired GM-CSF–dependent immunity in alveolar macrophages.