From: Primary immune regulatory disorders: Undiagnosed needles in the haystack?
Group | Disorder | Gene | Inheritance | Typical features |
---|---|---|---|---|
Regulatory T-lymphocyte defect (absent/reduced Tregs and/or functional Treg defect) | IPEX syndrome (immune dysregulation, polyendocrinopathy, enteropathy, X-linked) | FOXP3 | XL | Autoimmune enteropathy, early onset type 1 diabetes mellitus, eczema, thyroiditis, hemolytic anemia, thrombocytopenia, elevated IgE |
CTLA4 haploinsufficiency | CTLA4 | AD | Autoimmunity particularly cytopenias, enteropathy, type 1 diabetes, lymphoproliferation, interstitial lung disease, recurrent infections, hypogammaglobulinemia | |
LRBA deficiency | LRBA | AR | Autoimmunity particularly cytopenias, lymphoproliferation, recurrent infections, enteropathy | |
STAT3 GOF | STAT3 | AD | Autoimmunity, lymphoproliferation, infections, short stature | |
CD25 deficiency | IL2RA | AR | Autoimmunity, lymphoproliferation | |
Autoimmune Lymphoproliferative Syndromes (ALPS) | ALPS-FAS (most common) | FAS | AD or AR | Lymphadenopathy, splenomegaly, hepatomegaly, autoimmune cytopenias, increased risk of lymphoma, defective lymphocyte apoptosis, elevated double negative T-cells. In ALPS-FAS, elevated soluble Fas Ligand, IL-10, vitamin B12, IgG |
ALPS-FASLG | TNFRSF6 | AR | ||
ALPS-Caspase10 | CASP10 | AD | ||
ALPS-Caspase8 | CASP8 | AR | ||
HLH – familial disorders | Perforin deficiency | PRF1 | AR | Early-onset HLH, fever, hepatosplenomegaly, cytopenias, decreased/absent NK and CTL activity |
Munc13-4 deficiency | UNC13D | AR | ||
Syntaxin 11 deficiency | STX11 | AR | ||
Munc18-2 deficiency | STXBP2 | AR | ||
HLH—IEI syndromes associated with increased incidence of HLH | Chediak Higashi syndrome | LYST | AR | Recurrent infections, partial oculocutaneous albinism, progressive neurological dysfunction, neutropenia, giant cytoplasmic granules |
Griscelli syndrome type 2 | RAB27A | AR | Partial albinism, neutropenia, thrombocytopenia, neurological impairment | |
Hermansky Pudlak syndrome type 2 | AP3B1 | AR | Oculocutaneous albinism, bleeding diathesis, neutropenia, hearing loss, pulmonary fibrosis | |
Hermansky Pudlak syndrome type 10 | AP3D1 | AR | Oculocutaneous albinism, bleeding diathesis, microcephaly, neurodevelopmental delay | |
X-linked lymphoproliferative disease 1 | SH2DIA | XL | EBV-associated HLH, lymphoma, aplastic anemia | |
X-linked lymphoproliferative disease 2 | XIAP | XL | EBV-associated HLH, colitis, hepatitis | |
Immune dysregulation with colitis/inflammatory bowel disease | IL-10 deficiency | IL10 | AR | Early onset severe colitis, respiratory tract infections, folliculitis, arthritis |
IL-10 receptor deficiency | IL10RA IL10RB | AR | ||
TGFB1 deficiency | TGFB1 | AR | Recurrent viral infections, microcephaly, encephalopathy | |
RIPK1 deficiency | RIPK1 | AR | Recurrent infections, arthritis | |
NFAT5 haploinsufficiency | NFAT5 | AD | Colitis, recurrent respiratory tract infections | |
Innate | STAT1 GOF | STAT1 | AD | Chronic mucocutaneous candidiasis, recurrent infections, autoimmunity |
NFKB2 deficiency | NFKB2 | AD | Recurrent sinopulmonary infections, endocrinopathies, low immunoglobulins | |
Thymic disorder | APECED | AIRE | AD or AR | Adrenal insufficiency, hypoparathyroidism, hypothyroidism, other autoimmunity, chronic mucocutaneous candidiasis |