. Author manuscript; available in PMC: 2014 Jan 7.

Published in final edited form as: J Allergy Clin Immunol. 2009 Aug 8;124(4):10.1016/j.jaci.2009.06.018. doi: 10.1016/j.jaci.2009.06.018

TABLE II.

Immunodeficiency syndromes and associated gastrointestinal disease

Immunodeficiency	Defect	Gastrointestinal manifestation
CVID	Multiple defects: TACI, inducible costimulator, T cell, cytokine; failure of B cells to differentiate into plasma cells	Chronic diarrhea, NLH, villous atrophy, IBD-like disease, pernicious anemia, hepatitis^{3–5,13,20–34}
Selective IgA deficiency	Gene defect unknown; defective maturation of B cells into IgA-secreting plasma cells	Diarrhea, celiac sprue, NLH^1,14–19,35
XLA	X-linked; defective Bruton tyrosine kinase → no mature B cells	Gastrointestinal disorders rare, chronic diarrhea, malabsorption ^{4,6,8–12,36}
Chronic granulomatous disease	Multiple defects: X-linked caused by defects in CYBB encoding the gp91^phox component of NADPH oxidase; autosomal recessive caused by defects in NCF1, NCF2, or CYBA defects in components of NADPH oxidase	Granulomatous colitis, perianal fistulae, hepatic abscess, gastric outlet obstruction, small-bowel obstruction, granulomatous stomatitis, oral ulcers, esophageal dysmotility^37–41
Wiskott-Aldrich syndrome	X-linked; defective WASP → poor cytoskeletal organization and defective signal transduction	Colitis, bloody diarrhea, malabsorption ^42–44
Severe combined immunodeficiency	Multiple defects: RAG1/2, JAK3, CD45, CD3 chain, ZAP70, Artemis, Ligase 4, IL2RG, IL-7Rα, ADA → defects in T and B cells	Chronic diarrhea, oral candidiasis, IBD^45–49
Bare lymphocyte syndrome	Multiple defects: RFX5, RFXAP and CIITA defects lead to MHC class II deficiency; TAP defects lead to MHC class I deficiency	Diarrhea, progressive liver disease, sclerosing cholangitis^49–53
X-linked hyper-IgM syndrome	X-linked; defective CD40 ligand on T cells → dysfunction in B-cell receptor for isotype switching	Cryptosporidium species enteropathy, sclerosing cholangitis, gastrointestinal carcinoma^54–59
Immune dysregulation, polyendocrinopathy, enteropathy (IPEX) syndrome	Mutation in forkhead box P3 gene (FOXP3) → no FOXP3 protein or mutant protein with abnormal regulatory T-cell function	Severe enteropathy with watery, often bloody diarrhea associated with eosinophilic inflammation ⁶⁰

TACI, Transmembrane activator and calcium-modulating ligand interactor; NADPH, nicotinamide adenine dinucleotide phosphate; NCF, neutrophil cytosolic factor; CYBB, cytochrome b beta subunit; WASP, Wiskott-Aldrich syndrome protein; RAG, recombinase-activating gene; JAK, Janus kinase; ZAP70, zeta-chain–associated protein kinase 70; IL2RG, interleukin-2 receptor gamma; ADA, adenosine deaminase deficiency; RFX5, regulatory factor X, 5; RFXAP, regulatory factor X-associated protein; CIITA, class II transactivator; TAP, transporter associated with antigen processing; FOXP3, forkhead box protein 3.