IEI with predominant susceptibility to infection
| Classification . | Clinical syndrome . | Rheumatologic/autoimmune manifestations . | Examples of genes identified . |
|---|---|---|---|
| SCID | Omenn syndrome | Lymphadenopathy, hepatosplenomegaly, increased IgE, and erythroderma | RAG1, ADA, RMRP, DLCRE1C, LIG4, IL2RG, and IL7RA |
| GVHD of transplacental maternal engraftment | Morbilliform erythema, papular dermatitis, and erythroderma | SCID-associated genes | |
| CID | CID-G/AI | Granulomas of the skin, mucosa, lungs, and adenoids ANCA vasculitis Autoimmune cytopenias Myasthenia gravis | RAG1 and RAG2 |
| HIGM syndrome | Increased circulating autoantibodies Increased risk of diabetes mellitus and autoimmune cytopenias | CD40L, CD40, AICDA, UNG, MSH6, CTNNBL1, and APRIL | |
| APDS | Lymphadenopathy, lymphoproliferation, and autoimmunity (cytopenias and glomerulonephritis) | PIK3CD and PIK3R1 | |
| Disorders of T cell activation | Inflammatory arthritis and IBD | ZAP70, SLP76, and LAT | |
| Deficiencies in thymic development | Omenn syndrome findings (FOXN1) | FOXN1 and TBX1 | |
| Chr22q11.2 microdeletion syndrome | Increased likelihood of ITP and JIA | Chr22q11.2 | |
| WAS | AIHA, vasculitis, and glomerulonephritis | WASP | |
| Predominantly antibody deficiency | CVID | SLE, IBD, chronic lung disease, and liver disease (hepatitis C, granulomas, and idiopathic liver disease) | TNFRSF13B (TACI), TNFRSF13C (BAFFR), CD19, CD21, CD81, NFKB1, NFKB2, and PTEN |
| Agammaglobulinemia | IBD, rheumatoid arthritis, fatigue, chronic diarrhea, rash, and joint pain | BTK and SPI1 |
| Classification . | Clinical syndrome . | Rheumatologic/autoimmune manifestations . | Examples of genes identified . |
|---|---|---|---|
| SCID | Omenn syndrome | Lymphadenopathy, hepatosplenomegaly, increased IgE, and erythroderma | RAG1, ADA, RMRP, DLCRE1C, LIG4, IL2RG, and IL7RA |
| GVHD of transplacental maternal engraftment | Morbilliform erythema, papular dermatitis, and erythroderma | SCID-associated genes | |
| CID | CID-G/AI | Granulomas of the skin, mucosa, lungs, and adenoids ANCA vasculitis Autoimmune cytopenias Myasthenia gravis | RAG1 and RAG2 |
| HIGM syndrome | Increased circulating autoantibodies Increased risk of diabetes mellitus and autoimmune cytopenias | CD40L, CD40, AICDA, UNG, MSH6, CTNNBL1, and APRIL | |
| APDS | Lymphadenopathy, lymphoproliferation, and autoimmunity (cytopenias and glomerulonephritis) | PIK3CD and PIK3R1 | |
| Disorders of T cell activation | Inflammatory arthritis and IBD | ZAP70, SLP76, and LAT | |
| Deficiencies in thymic development | Omenn syndrome findings (FOXN1) | FOXN1 and TBX1 | |
| Chr22q11.2 microdeletion syndrome | Increased likelihood of ITP and JIA | Chr22q11.2 | |
| WAS | AIHA, vasculitis, and glomerulonephritis | WASP | |
| Predominantly antibody deficiency | CVID | SLE, IBD, chronic lung disease, and liver disease (hepatitis C, granulomas, and idiopathic liver disease) | TNFRSF13B (TACI), TNFRSF13C (BAFFR), CD19, CD21, CD81, NFKB1, NFKB2, and PTEN |
| Agammaglobulinemia | IBD, rheumatoid arthritis, fatigue, chronic diarrhea, rash, and joint pain | BTK and SPI1 |
A summary of the major IEI that present with predominant susceptibility to infections, categorized into SCID, CID, CID with syndromic features, and predominantly antibody deficiencies. ANCA, antineutrophil cytoplasmic antibody; WASP, WAS protein.