Besides unique patients with immunodeficiency and immunodysregulation disorders lacking known diagnoses, our intake includes patients with combined immunodeficiency, variants of hyper-IgE syndrome, variants of autoimmune lymphoproliferative syndrome (ALPS) or caspase-8-deficiency state (CEDS), common variable immunodeficiency (CVID), X-linked Magnesium defect with EBV infection and Neoplasia (XMEN), variants of PASLI (p110 delta activation mutation causing senescent T cells, lymphadenopathy, and immunodeficiency) disease, and Evans syndrome. Our evaluation includes functional screening and gene sequencing, and a subset of patients is also being intensively studied using biochemical analyses, gene expression microarrays, flow cytometric analyses, in vitro functional tests, and other technologies. These experiments have provided leads for sequencing of new candidate genes not previously associated with disease. Additionally, we are using comparative genomic hybridization (CGH) arrays, whole exome sequencing, and other technologies to determine genetic causes of new immunological diseases in an unbiased manner. In FY2014, using these approaches, we identified from our hyperimmunoglobulinemia E cohort a new disease. This disease is characterized by immune deficiency with recurrent pulmonary and other infections, severe atopic dermatitis and cutaneous vasculitis, autoimmunity including glomerulonephritis and cytopenias, motor and neurocognitive impairment, and lymphoma. We found that this disease is caused by autosomal recessive hypomorphic mutations in the phosphoglucomutase 3 (PGM3) gene, making this a new congenital disorder of glycosylation. The defect in glycolylation affects various immune functions, including the expression of CTLA4, a regulator that normally dampens adaptive immune responses to prevent autoimmunity. Our findings will improve diagnosis, provide new insight into how glycosylation regulates the immune system works to prevent allergy and infection, and also suggest potential therapeutic approaches.

Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Niaid Extramural Activities
Zip Code
Su, Helen (2017) Studying human immunodeficiencies in humans: advances in fundamental concepts and therapeutic interventions. F1000Res 6:318
Abolhassani, Hassan; Edwards, Emily S J; Ikinciogullari, Aydan et al. (2017) Combined immunodeficiency and Epstein-Barr virus-induced B cell malignancy in humans with inherited CD70 deficiency. J Exp Med 214:91-106
Takeda, Andrew J; Zhang, Yu; Dornan, Gillian L et al. (2017) Novel PIK3CD mutations affecting N-terminal residues of p110? cause activated PI3K? syndrome (APDS) in humans. J Allergy Clin Immunol 140:1152-1156.e10
Randolph, Adrienne G; Yip, Wai-Ki; Allen, Emma Kaitlynn et al. (2017) Evaluation of IFITM3 rs12252 Association With Severe Pediatric Influenza Infection. J Infect Dis 216:14-21
Lamborn, Ian T; Jing, Huie; Zhang, Yu et al. (2017) Recurrent rhinovirus infections in a child with inherited MDA5 deficiency. J Exp Med 214:1949-1972
Ozen, Ahmet; Comrie, William A; Ardy, Rico C et al. (2017) CD55 Deficiency, Early-Onset Protein-Losing Enteropathy, and Thrombosis. N Engl J Med 377:52-61
Eccleston, J L; Su, H; Ling, A et al. (2016) Gastrointestinal: Adult presentation of intestinal malrotation. J Gastroenterol Hepatol 31:1382
Lo, Bernice; Fritz, Jill M; Su, Helen C et al. (2016) CHAI and LATAIE: new genetic diseases of CTLA-4 checkpoint insufficiency. Blood 128:1037-42
Lovell, Jana P; Foruraghi, Ladan; Freeman, Alexandra F et al. (2016) Persistent nodal histoplasmosis in nuclear factor kappa B essential modulator deficiency: Report of a case and review of infection in primary immunodeficiencies. J Allergy Clin Immunol 138:903-905
Buchbinder, David; Stinson, Jeffrey R; Nugent, Diane J et al. (2015) Mild B-cell lymphocytosis in patients with a CARD11 C49Y mutation. J Allergy Clin Immunol 136:819-821.e1

Showing the most recent 10 out of 36 publications