Laboratory evaluation of the immune system
- Francisco A Bonilla, MD, PhD
Francisco A Bonilla, MD, PhD
- Section Editor — Immunology and Immunodeficiency
- Associate Professor of Pediatrics
- Harvard Medical School
- E Richard Stiehm, MD
E Richard Stiehm, MD
- Editor-in-Chief — Allergy and Immunology
- Section Editor — Immunology and Immunodeficiency
- Distinguished Research Professor of Pediatrics
- David Geffen School of Medicine at UCLA
Immune deficiency most often comes to clinical attention because of an increase in the incidence or severity of infectious illness beyond what is considered "normal." This topic review will provide a general approach to the laboratory evaluation of the immune system, beginning with screening tests and progressing through the indications for more advanced immunologic testing. Indications for referral to a specialist are discussed, and links to more detailed topics about the different groups of disorders are provided here and throughout the topic. (See "Primary humoral immunodeficiencies: An overview" and "Combined immunodeficiencies" and "Primary disorders of phagocytic function: An overview" and "Laboratory evaluation of neutrophil disorders" and "Overview and clinical assessment of the complement system".)
INITIAL APPROACH TO THE PATIENT
Immune deficiency disorders should be considered once the more common causes of recurrent infection have been excluded. The initial approach to a child or adult with recurrent infections is described separately. (See "Approach to the child with recurrent infections" and "Approach to the adult with recurrent infections".)
Immune dysregulation can result in disorders other than recurrent infections, including:
- Autoimmune disorders, such as autoimmune hemolytic anemia.
- Inflammatory disorders, such as inflammatory bowel disease or inflammatory arthritis.
- Malignancies, such as lymphoma.
- Allergic disease, such as atopic dermatitis, food allergy, and allergic rhinosinusitis and asthma.
Before initiating immunologic testing, the clinician should perform a thorough clinical history and physical examination. In infants and children, height and weight records should be reviewed, as failure to thrive and poor growth are consistent with immunodeficiency. In patients with possible immunodeficiency, important elements of the clinical presentation include:
- National Library of Medicine compilation of sites for specific Gene Testing. http://ncbi.nih.gov/sites/GeneTests/review.
- GeneDX: www.genedx.com (Accessed on June 02, 2011).
- Correlagen Diagnostics: www.correlagen.com (Accessed on June 02, 2011).
- In the United States, Children's Hospitals with expertise in diagnostic testing for primary immunodeficiencies include Cincinnati Children's Hospital Medical Center (www.cincinnatichildrens.org), Children's Hospital of Wisconsin in Milwaukee (www.chw.org) and Seattle Children's Hospital (www.seattlechildrens.org).
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- The Complement Laboratory of the National Jewish Mecial Center, Denver, CO.
- Netea MG, van de Veerdonk FL, van Deuren M, van der Meer JW. Defects of pattern recognition: primary immunodeficiencies of the innate immune system. Curr Opin Pharmacol 2011; 11:412.
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- Chou J, Ohsumi TK, Geha RS. Use of whole exome and genome sequencing in the identification of genetic causes of primary immunodeficiencies. Curr Opin Allergy Clin Immunol 2012; 12:623.
- Conley ME, Dobbs AK, Quintana AM, et al. Agammaglobulinemia and absent B lineage cells in a patient lacking the p85α subunit of PI3K. J Exp Med 2012; 209:463.
- Zhou Q, Lee GS, Brady J, et al. A hypermorphic missense mutation in PLCG2, encoding phospholipase Cγ2, causes a dominantly inherited autoinflammatory disease with immunodeficiency. Am J Hum Genet 2012; 91:713.
- McDonald-McGinn DM, Fahiminiya S, Revil T, et al. Hemizygous mutations in SNAP29 unmask autosomal recessive conditions and contribute to atypical findings in patients with 22q11.2DS. J Med Genet 2013; 50:80.
- Keller MD, Ganesh J, Heltzer M, et al. Severe combined immunodeficiency resulting from mutations in MTHFD1. Pediatrics 2013; 131:e629.
- Moshous D, Martin E, Carpentier W, et al. Whole-exome sequencing identifies Coronin-1A deficiency in 3 siblings with immunodeficiency and EBV-associated B-cell lymphoproliferation. J Allergy Clin Immunol 2013; 131:1594.
- Greil J, Rausch T, Giese T, et al. Whole-exome sequencing links caspase recruitment domain 11 (CARD11) inactivation to severe combined immunodeficiency. J Allergy Clin Immunol 2013; 131:1376.
- INITIAL APPROACH TO THE PATIENT
- Physical examination
- Initial screening laboratory tests
- CATEGORIES AND PREVALENCE OF IMMUNE DEFICIENCIES
- OVERVIEW OF CLINICAL MANIFESTATIONS AND TESTING FOR SPECIFIC COMPONENTS OF THE IMMUNE SYSTEM
- Antibody deficiency and defects
- - Measurement of antibody levels
- - Measurement of antibody function
- Measurement of immune globulin loss
- Defects in cellular immunity
- - Complete blood count with differential and blood smear
- Evaluation of lymphopenia
- - Cutaneous delayed-type hypersensitivity
- - Flow cytometry
- Abnormalities in immunodeficiency
- - Advanced tests
- - In vitro studies of T cell function
- Response to mitogens
- Response to specific antigens
- Neutrophil defects (defects in phagocyte function)
- - Evaluation of neutrophil numbers
- - Evaluation of neutrophil function
- Complement defects
- Innate immune defects
- - Natural killer cell defects
- - Defects of IL-12/23-IFN-gamma pathways
- - Toll-like receptor pathway defects
- Advanced genomic studies
- SUMMARY AND RECOMMENDATIONS