Table 1. Characteristics and treatment options in PIDs with autoimmunity/immune dysregulation.

Disease	Gene mutation /Inheritance	Clinical features	Immune phenotype	Treatment options
CTLA4 deficiency	CTLA4/AD	Recurrent infections, autoimmunity/ immune dysregulation (cytopenia, enteropathy, GLILD)	Hypogammaglobulinemia, CD4+ T-cell lymphopenia, defective B cell maturation with progressive B lymphopenia and impaired response to immunizations	Antimicrobial prophylaxis,immunoglobulinreplacement,Immunosuppressants,rituximab, abatacept,belatacept, vedolizumabHSCT
LRBA deficiency	LRBA/AR	Recurrent infections, autoimmunity/ immune dysregulation (including cytopenia, enteropathy, GLILD, hepatitis, myasthenia gravis, uveitis, alopecia, polyarthritis and diabetes) Nonmalignant lymphoproliferation (lympadenopathy, hepatosplenomegaly) Increased risk of gastric adenocarcinoma and other malignancies	Hypogammaglobulinemia with normal B cell levels but low memory B cells and impaired response to immunizations. Normal T cell levels but decreased Tregs and increased double-negative T cells andcTFH	Antimicrobial prophylaxis, immunoglobulin replacement, Immunosuppressants, rituximab, abataceptHSCT
APDS 1 and 2	PIK3CD,PIK3R1/AD	Recurrent bacterial and viral infections, nonmalignant lymphoproliferation (lympadenopathy, hepatosplenomegaly and focal nodular lymphoid hyperplasia), autoimmunity/ immune dysregulation (including cytopenia, arthritis, enteropathy glomerulonephritis and sclerosing cholangitis),increased risk of lymphoma and malignances, developmental delay(APDS 2)	Hypogammaglobulinemia (variable degree of low IgG and IgA and high IgM levels), low memory B cells, high transitional B cells and impaired response to immunizations, low naiveCD4 and CD8 T-cells, andincreased CD8 effector T-cells, TFH cells and CD57+ senescent T cell levels	Antimicrobial prophylaxis, immunoglobulin replacement, Immunosuppressants, rituximab, mTOR target therapy (i.e, rapamycin), selective PI3Kd inhibitors (i.e. leniolisib, seletalisib nemiralisib under trials)HSCT
STAT1 GOF disease	STAT1/AD	Recurrent infections, Hypogammaglobulinemia, chronic mucocutaneous candidiasis variable decreased levels and/ Autoimmunity/ immune dysregulation or function of T, B, and/or (including hypothyroidism, cytopenia, NK cells, decreased Hi17 diabetes, systemic lupus erythematosus, cells and IL17 production enteropathy, arthritis, and multiple sclerosis),Increased risk of cerebral aneurysms and vasculopathy	Antimicrobial prophylaxis, immunoglobulin replacement therapy, immunosuppressants, jakinibs (i.e. tofacitinib, ruxolitinib and baricitinib, filgotinib and upadacitinib), HSCT
STAT3 GOF disease	STAT3/AD	Recurrent infections, Autoimmunity/immune dysregulation (including diabetes, enteropathy, hypothyroidism, cytopenia), nonmalignant lymphoproliferation (lymphadenopathy, hepatosplenomegaly and lymphocytic interstitial pneumonia), short stature	Hypogammaglobulinemia, variable degree of T/B/ NK-cell lymphopenia with a low number of Treg cells, increased levels of double-negative TCR(xP+ T cells and decreased TH17 cells, terminal B cell maturation arrest	Antimicrobial prophylaxis, immunoglobulin replacement therapy, immunosuppressants, tocilizumab, jakinibs
CTLA4, Cytotoxic T-lymphocyte antigen 4; LRBA, Lipopolysaccharide-responsive beige-like anchor; APDS, Activated phosphoinositide 3-kinase 8 syndrome; PIK3, Phosphoinositide-3-kinases; STAT, Signal transducer and activator of transcription; GLILD, Granulomatous and Lymphocytic Interstitial Lung Disease; GOF, gain of function; AD, autosomal dominant; AR, autosomal recessive; HSCT, hematopoietic stem cell transplantation.