Table 4.

Gastrointestinal manifestations in primary immunodeficiencies [58]

Immunodeficiency	Evaluation with clinically significant result	Gastrointestinal manifestation
Common variable immunodeficiency	Quantitative immunoglobulins → reduced serum IgG and IgA and/or IgM; antibody response (IgG) to vaccination → poor, nonprotective; lymphocyte subsets → normal or reduced B cell numbers	Diarrhea, nodular lymphoid hyperplasia, flat villous lesions, IBD-like disease, pernicious anemia
Selective IgA deficiency	Quantitative immunoglobulins → serum IgA absent or near absent usually <10 mg/dl; normal IgG and IgM levels though IgG2 subclass deficiency may be present	Diarrhea, celiac sprue, nodular lymphoid hyperplasia
Agammaglobulinemia, X-linked or autosomal recessive	Quantitative immunoglobulins → reduced serum levels of all immunoglobulins; antibody response (IgG) to vaccination → poor, nonprotective; lymphocyte subsets → normal numbers of pro-B cells; reduced/absent B cells	Gastrointestinal disorders rare, chronic diarrhea, malabsorption
X-linked hyper IgM syndrome	Quantitative immunoglobulins → normal to elevated IgM levels; low IgG and IgA; antibody response (IgG) to vaccination → poor, nonprotective; lymphocyte subsets → normal T cell numbers; B cell numbers are normal or slightly reduced	Diarrhea, progressive liver disease, sclerosing cholangitis
Severe combined immunodeficiency	Lymphocyte subsets → markedly diminished T cells; variable B cell and natural killer cell numbers depending on functional deficiency; in vitro assay of lymphocyte function → diminished response to mitogens-PHA, ConA, PWM	Diarrhea, oral candidiasis
DiGeorge syndrome	Quantitative immunoglobulins → immunoglobulins are usually normal though occasionally IgE is elevated and IgA may be reduced; lymphocyte subsets → variable decreases in T lymphocytes; B and natural killer cells are normal or elevated; in vitro assay of lymphocyte function → variable lymphocyte response to mitogens depending on thymic deficiency	Mucocutaneous candidiasis
Immune dysregulation, polyendocrinopathy, enteropathy syndrome	Complete blood count → eosinophilia; quantitative immunoglobulins → may have increased serum IgE and IgA; lymphocyte subsets → CD4+CD25+ T cells are reduced most patients with FOXP3 mutations have markedly decreased or absent FOXP3+ Tregs; otherwise normal T cell and B cell subsets; in vitro assay of lymphocyte function → specific antigens are normal or slightly decreased	Severe enteropathy with watery often bloody diarrhea associated with eosinophilic inflammation
Bare lymphocyte syndrome	Quantitative immunoglobulins → variable reductions; antibody response (IgG) to vaccination → poor, nonprotective; lymphocyte subsets → low numbers of CD4+ T cells with proportional increases in CD8+ T cells; flow cytometry-diminished expression of MHC; in vitro assay of lymphocyte function → impaired antigen specific responses	Progressive liver disease, sclerosing cholangitis
Chronic granulomatous disease	Dihydrorhodamine reductase or nitroblue tetrazolium → diminished respiratory burst in neutrophils	Colitis, hepatic abscess, gastric outlet obstruction, small bowel obstruction, granulomatous stomatitis, oral ulcers, esophageal dysmotility
Wiskott–Aldrich syndrome	Complete blood count → platelet numbers are reduced and small in size; quantitative immunoglobulins → variable concentrations secondary to accelerated synthesis and catabolism of Igs (usually low IgM, elevated IgA and IgE, and normal or slightly low IgG); antibody response (IgG) to vaccination → impaired antibody response; lymphocyte subsets → moderate reductions in percentages of CD3+, CD4+, and CD8+ bearing T cells; in vitro assay of lymphocyte function → impaired lymphocyte response to mitogens	Colitis, bloody diarrhea, malabsorption
Hermansky–Pudlak syndrome	Complete blood count → normal platelet count; coagulation studies → prolonged bleeding time, with abnormal platelet function assays	Granulomatous colitis

IBD, inflammatory bowel disease; ConA, concanavalin A; FOXP3, forkhead box P3; MHC, major histocompatibility complex; PHA, phytohaemagglutinin; PWM, pokeweed mitogen.

Adapted from [58].