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) | IFNGR1 IFNGR2 | IFNG IFNGR1 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 |
| 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) | IFNGR1 IFNGR2 | IFNG IFNGR1 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 |
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.