IEI with described ILC abnormalities: Clinical characteristics
| Disease . | Gene . | Inheritance . | OMIM . | IUIS tables major category; subcategory . | Microbial susceptibility . | Immune dysregulation . |
|---|---|---|---|---|---|---|
| gc deficiency SCID | IL2RG | XL | 308380 | T1; ST1 | Recurrent severe viral, bacterial, and fungal infections; diarrhea | Treg defects; hypomorphic mutations in IL-2Rγ result in CID with immune dysregulation |
| JAK3 deficiency SCID | JAK3 | AR | 600173 | T1; ST1 | Recurrent or severe respiratory infections; oral thrush (candidiasis); pneumonia | Treg defects |
| IL7Ra deficiency SCID | IL7R | AR | 146661 | T1; ST1 | Recurrent severe viral, bacterial, and fungal infections; candidiasis; chronic diarrhea; Pneumocystis jirovecii pneumonia | Treg defects; may present with immune dysregulation; chronic inflammatory diseases |
| RAG1 deficiency SCID | RAG1 | AR | 179615 | T1; ST2 | Recurrent severe viral, bacterial, and fungal infections; Pneumocystis jirovecii; neutralizing antitype I IFN antibodies associated with varicella infection | Hypomorphic mutations associated with immune dysregulation |
| RAG2 deficiency SCID | RAG2 | AR | 179616 | T1; ST2 | Recurrent severe viral, bacterial, and fungal infections; Pneumocystis jirovecii; neutralizing antitype I IFN antibodies associated with varicella infection | Hypomorphic mutations associated with immune dysregulation |
| RORgt deficiency | RORC | AR | 616622 | T6; ST1 | Mycobacteria and Candida albicans | No broad infectious or autoimmune phenotype |
| IL-12Rb2 deficiency | IL12RB2 | AR | 601642 | T6; ST1 | Mycobacteria and Salmonella | Deficiency is associated with autoimmunity in mice; human data are scarce |
| IL-23R deficiency | IL23R | AR | 607562 | T6; ST1 | Mycobacteria and Salmonella | SNPs associated with autoimmunity, not null or LOF |
| IL-12R and IL-23Rb1 deficiency | IL12RB1 | AR | 601604 | T6; ST1 | Mycobacteria and Salmonella | Only 3 out of 300 LOF showed autoimmunity; SNPs associated with autoimmunity |
| LAD1 | ITGB2 | AR | 600065 | T5; ST2 | Recurrent bacterial and fungal infections | Leukocytosis |
| DOCK8 deficiency (HIES) | DOCK8 | AR | 243700 | T1; ST3 | Recurrent cutaneous viral, fungal, and staphylococcal infections | Treg defects; low NK cells with poor function; eosinophilia; severe atopy; cancer diathesis |
| WAS LOF | WAS | XL | 300392 | T2; ST1 | Recurrent viral and bacterial infections | Thrombocytopenia with small platelets; eczema; lymphoma; autoimmune disease; IgA nephropathy; vasculitis; XL thrombocytopenia is a mild form of WAS—bloody diarrhea; Treg defects |
| ITK deficiency | ITK | AR | 186973 | T1; ST3 | Epstein–Barr virus (EBV) | EBV-associated B cell lymphoproliferation; lymphoma |
| BCL11B deficiency | BCL11B | AD | 617237 | T2; ST9 | Upper respiratory infections | Immunological dysregulation expressed as allergy, asthma, eczema, eosinophilia, and severe atopy |
| DIAPH1 deficiency | DIAPH1 | AR | 602121 | T2; ST9 | Recurrent viral and bacterial infections | B lymphoma; decreased T cell activation/proliferation in vitro; impaired adhesion/microtubule organizing center (MTOC repositioning to immune synapse; defective cytoskeletal organization; mitochondrial dysfunction in SCBMS pathogenesis |
| STAT3 LOF (HIES) | STAT3 (LOF, DN) | AD | 102582 | T2; ST5 | Bacterial infections—boils and pulmonary abscesses, pneumatoceles due to Staphylococcusaureus; Pulmonary aspergillus; Pneumocystis jirovecii; mucocutaneous candidiasis | Eczema |
| BTK deficiency (XLA) | BTK | XL | 300300 | T3; ST1 | Severe bacterial infections | Normal numbers of pro-B cells |
| CVID, no gene defect specified | Unknown | Variable | 607594 616576 615577 240500 614700 604558 | T3; ST2 | Recurrent infections | Some show polyclonal lymphoproliferation, autoimmune cytopenias, and/or granulomatous disease |
| Disease . | Gene . | Inheritance . | OMIM . | IUIS tables major category; subcategory . | Microbial susceptibility . | Immune dysregulation . |
|---|---|---|---|---|---|---|
| gc deficiency SCID | IL2RG | XL | 308380 | T1; ST1 | Recurrent severe viral, bacterial, and fungal infections; diarrhea | Treg defects; hypomorphic mutations in IL-2Rγ result in CID with immune dysregulation |
| JAK3 deficiency SCID | JAK3 | AR | 600173 | T1; ST1 | Recurrent or severe respiratory infections; oral thrush (candidiasis); pneumonia | Treg defects |
| IL7Ra deficiency SCID | IL7R | AR | 146661 | T1; ST1 | Recurrent severe viral, bacterial, and fungal infections; candidiasis; chronic diarrhea; Pneumocystis jirovecii pneumonia | Treg defects; may present with immune dysregulation; chronic inflammatory diseases |
| RAG1 deficiency SCID | RAG1 | AR | 179615 | T1; ST2 | Recurrent severe viral, bacterial, and fungal infections; Pneumocystis jirovecii; neutralizing antitype I IFN antibodies associated with varicella infection | Hypomorphic mutations associated with immune dysregulation |
| RAG2 deficiency SCID | RAG2 | AR | 179616 | T1; ST2 | Recurrent severe viral, bacterial, and fungal infections; Pneumocystis jirovecii; neutralizing antitype I IFN antibodies associated with varicella infection | Hypomorphic mutations associated with immune dysregulation |
| RORgt deficiency | RORC | AR | 616622 | T6; ST1 | Mycobacteria and Candida albicans | No broad infectious or autoimmune phenotype |
| IL-12Rb2 deficiency | IL12RB2 | AR | 601642 | T6; ST1 | Mycobacteria and Salmonella | Deficiency is associated with autoimmunity in mice; human data are scarce |
| IL-23R deficiency | IL23R | AR | 607562 | T6; ST1 | Mycobacteria and Salmonella | SNPs associated with autoimmunity, not null or LOF |
| IL-12R and IL-23Rb1 deficiency | IL12RB1 | AR | 601604 | T6; ST1 | Mycobacteria and Salmonella | Only 3 out of 300 LOF showed autoimmunity; SNPs associated with autoimmunity |
| LAD1 | ITGB2 | AR | 600065 | T5; ST2 | Recurrent bacterial and fungal infections | Leukocytosis |
| DOCK8 deficiency (HIES) | DOCK8 | AR | 243700 | T1; ST3 | Recurrent cutaneous viral, fungal, and staphylococcal infections | Treg defects; low NK cells with poor function; eosinophilia; severe atopy; cancer diathesis |
| WAS LOF | WAS | XL | 300392 | T2; ST1 | Recurrent viral and bacterial infections | Thrombocytopenia with small platelets; eczema; lymphoma; autoimmune disease; IgA nephropathy; vasculitis; XL thrombocytopenia is a mild form of WAS—bloody diarrhea; Treg defects |
| ITK deficiency | ITK | AR | 186973 | T1; ST3 | Epstein–Barr virus (EBV) | EBV-associated B cell lymphoproliferation; lymphoma |
| BCL11B deficiency | BCL11B | AD | 617237 | T2; ST9 | Upper respiratory infections | Immunological dysregulation expressed as allergy, asthma, eczema, eosinophilia, and severe atopy |
| DIAPH1 deficiency | DIAPH1 | AR | 602121 | T2; ST9 | Recurrent viral and bacterial infections | B lymphoma; decreased T cell activation/proliferation in vitro; impaired adhesion/microtubule organizing center (MTOC repositioning to immune synapse; defective cytoskeletal organization; mitochondrial dysfunction in SCBMS pathogenesis |
| STAT3 LOF (HIES) | STAT3 (LOF, DN) | AD | 102582 | T2; ST5 | Bacterial infections—boils and pulmonary abscesses, pneumatoceles due to Staphylococcusaureus; Pulmonary aspergillus; Pneumocystis jirovecii; mucocutaneous candidiasis | Eczema |
| BTK deficiency (XLA) | BTK | XL | 300300 | T3; ST1 | Severe bacterial infections | Normal numbers of pro-B cells |
| CVID, no gene defect specified | Unknown | Variable | 607594 616576 615577 240500 614700 604558 | T3; ST2 | Recurrent infections | Some show polyclonal lymphoproliferation, autoimmune cytopenias, and/or granulomatous disease |
XL, X-linked; AD, autosomal dominant; AR, autosomal recessive; T, table; ST, sub-table; SCBMS, seizures, cortical blindness, microcephaly syndrome.