| Gene . | Clinical features . | Cellular defects and mechanisms of disease . |
|---|---|---|
| IL2RG (X-linked) | B+T−NK− SCID; recurrent, severe, and often fatal microbial infections; impaired B cell responses due to lack of T cell help | Persistent B cell defect (poor responses in vivo, ↓ total and class-switched memory B cells) after HSCT in nonconditioned patients due to intrinsic B cell requirement of IL-21R/γc/JAK3 cytokine signaling |
| JAK3 (AR) | ||
| STAT3 (AD DN) | S. aureus, Streptococcus pneumonia, and C. albicans infections; eczema; vascular/musculoskeletal/dental/ connective tissue defects; impaired humoral immunity; and hyper-IgE | ↓Memory B cells in vivo; ↓ naive B cell plasmablast differentiation in vitro to IL-21; ↓ IL-21–dependent upregulation ofIL2RA expression, impairing responses to IL-2; ↓ Tfh memory cells in vivo; ↓ Tfh cell generation from naive CD4+ T cells in vitro |
| ZNF341 (AR) | ||
| IL21R/IL21 (AR) | Combined immunodeficiency; disseminated cryptosporidium infection, susceptibility toPneumocystis jirovecii and fungal infections; impaired humoral immunity; hypogammaglobulinemia; increased serum IgE | ↓ Total memory and class-switched memory B cells in vivo; ↓ naive B cell differentiation into plasmablasts in vitro to IL-21; ↓ Tfh memory CD4+ T cells in vivo; ↓ Tfh cells from naive CD4+ T cells in vitro |
| Gene . | Clinical features . | Cellular defects and mechanisms of disease . |
|---|---|---|
| IL2RG (X-linked) | B+T−NK− SCID; recurrent, severe, and often fatal microbial infections; impaired B cell responses due to lack of T cell help | Persistent B cell defect (poor responses in vivo, ↓ total and class-switched memory B cells) after HSCT in nonconditioned patients due to intrinsic B cell requirement of IL-21R/γc/JAK3 cytokine signaling |
| JAK3 (AR) | ||
| STAT3 (AD DN) | S. aureus, Streptococcus pneumonia, and C. albicans infections; eczema; vascular/musculoskeletal/dental/ connective tissue defects; impaired humoral immunity; and hyper-IgE | ↓Memory B cells in vivo; ↓ naive B cell plasmablast differentiation in vitro to IL-21; ↓ IL-21–dependent upregulation ofIL2RA expression, impairing responses to IL-2; ↓ Tfh memory cells in vivo; ↓ Tfh cell generation from naive CD4+ T cells in vitro |
| ZNF341 (AR) | ||
| IL21R/IL21 (AR) | Combined immunodeficiency; disseminated cryptosporidium infection, susceptibility toPneumocystis jirovecii and fungal infections; impaired humoral immunity; hypogammaglobulinemia; increased serum IgE | ↓ Total memory and class-switched memory B cells in vivo; ↓ naive B cell differentiation into plasmablasts in vitro to IL-21; ↓ Tfh memory CD4+ T cells in vivo; ↓ Tfh cells from naive CD4+ T cells in vitro |
AD, autosomal dominant; NK, natural killer.