Immunoglobulin Disorders

  • Diagnosis
  • Algorithms
  • Background
  • Lab Tests
  • References
  • Related Topics
  • Videos

Indications for Testing

  • Recurrent infections (eg, sinusitis, otitis media, pneumonia) and/or chronic diarrhea

Laboratory Testing

  • Initial screening
    • General immunodeficiency screening
      • CBC with differential
      • Comprehensive metabolic profile
      • Quantitative serum immunoglobulins (IgA, IgG, IgM)
        • IgG normal but suspicion for deficiency – perform IgG subclass testing
        • Elevated immunoglobulins may require further evaluation including mutation testing to confirm uncommon disorders (eg, hyper-IgM syndrome)
      • Lymphocyte subset analyses – depending on clinical presentation
      • Pre and postvaccination titers – most useful if presentation is solely recurrent sinopulmonary disease, or normal quantitative immunoglobulins
    • Rule out other diseases associated with immunodeficiency
    • Rule out diseases associated with protein losses (eg, protein-losing enteropathy, nephropathy)
  • More specific screening – based on initial screening results
    • Choice of testing based on initial screening results
    • Clinical presentation may require multiple immune system investigations (see Immunodeficiency Evaluation algorithms)
    • Definitive diagnosis, prognostication, and treatment may require genetic testing in consultation with genetic counselor

Immunoglobulin deficiencies are the most common primary immunodeficiency.

Epidemiology

  • Incidence – 1/2,000 live births for primary immunodeficiency

Specific Immunoglobulins

  • Structure – 2 heavy chains, 2 light chains
    • Isotype (G, M, A, D, E) – determined by type of heavy chain

Tests generally appear in the order most useful for common clinical situations. Click on number for test-specific information in the ARUP Laboratory Test Directory.

Immunoglobulins (IgA, IgG, IgM), Quantitative 0050630
Method: Quantitative Nephelometry

Immunoglobulin G Subclasses (1, 2, 3, 4) 0050577
Method: Quantitative Nephelometry

Lymphocyte Subset Panel 6 - Total Lymphocyte Enumeration with CD45RA and CD45RO 0095862
Method: Quantitative Flow Cytometry

Lymphocyte Subset Panel 7 - Congenital Immunodeficiencies 0095899
Method: Quantitative Flow Cytometry

Regulatory T-Cell Panel 2010172
Method: Quantitative Flow Cytometry

Streptococcus pneumoniae Antibodies, IgG (23 Serotypes) 2005779
Method: Quantitative Multiplex Bead Assay

Streptococcus pneumoniae Antibodies, IgG (14 Serotypes) 0050725
Method: Quantitative Multiplex Bead Assay

Streptococcus pneumoniae Antibodies, IgG (9 Serotypes) 2008919
Method: Quantitative Multiplex Bead Assay

Diphtheria, Tetanus, and H. Influenzae b Antibodies, IgG 0050779
Method: Quantitative Multiplex Bead Assay

Hyper IgM Syndrome Panel, Sequencing (12 Genes) and Deletion/Duplication (10 Genes) 2011154
Method: Massively Parallel Sequencing/Exonic Oligonucleotide-based CGH Microarray

Limitations

Not determined or evaluated – mutations in genes not included on the panel; deep intronic and regulatory region mutations; breakpoints for large deletions/duplications; translocations

Deletions/duplications will not be detected in IKBKG or PIK3CD

Small deletions or insertions may not be detected

Diagnostic errors can occur due to rare sequence variations

Lack of a detectable gene mutation does not exclude a diagnosis of hyper-IgM syndrome

Primary Antibody Deficiency Panel, Sequencing (35 Genes) and Deletion/Duplication (26 Genes) 2011156
Method: Massively Parallel Sequencing/Exonic Oligonucleotide-based CGH Microarray

Limitations

Not determined or evaluated – mutations in genes not included on the panel; deep intronic and regulatory region mutations; breakpoints for large deletions/duplications; translocations

Deletions/duplications will not be detected in IKBKG, LRBA, LRRC8A, PIK3CD, PIK3R1, PLCG2, PRKCD, SH2D1A, or XIAP/BIRC4 genes

Small deletions or insertions may not be detected

Diagnostic errors can occur due to rare sequence variations

Lack of a detectable gene mutation does not exclude a diagnosis of primary antibody deficiency

Related Tests

General References

About Primary Immunodeficiencies - Specific Disease Types. Immune Deficiency Foundation. Towson, MD [Accessed: Nov 2015]

Al-Herz W, Bousfiha A, Casanova J, Chatila T, Conley MEllen, Cunningham-Rundles C, Etzioni A, Franco JLuis, Gaspar B, Holland SM, Klein C, Nonoyama S, Ochs HD, Oksenhendler E, Picard C, Puck JM, Sullivan K, Tang ML K. Primary immunodeficiency diseases: an update on the classification from the international union of immunological societies expert committee for primary immunodeficiency. Front Immunol. 2014; 5: 162. PubMed

Ballow M, Notarangelo L, Grimbacher B, Cunningham-Rundles C, Stein M, Helbert M, Gathmann B, Kindle G, Knight AK, Ochs HD, Sullivan K, Franco JL. Immunodeficiencies. Clin Exp Immunol. 2009; 158 Suppl 1: 14-22. PubMed

Davies G, Thrasher AJ. Update on the hyper immunoglobulin M syndromes. Br J Haematol. 2010; 149(2): 167-80. PubMed

Freeman AF, Holland SM. The hyper-IgE syndromes. Immunol Allergy Clin North Am. 2008; 28(2): 277-91, viii. PubMed

Gouilleux-Gruart V, Schleinitz N, Fischer A. Primary immune deficiencies: practical questions. Curr Opin Allergy Clin Immunol. 2013; 13 Suppl 2: S67-78. PubMed

Latiff AH Abdul, Kerr MA. The clinical significance of immunoglobulin A deficiency. Ann Clin Biochem. 2007; 44(Pt 2): 131-9. PubMed

Locke BA, Dasu T, Verbsky JW. Laboratory diagnosis of primary immunodeficiencies. Clin Rev Allergy Immunol. 2014; 46(2): 154-68. PubMed

Morimoto Y, Routes JM. Immunodeficiency overview. Prim Care. 2008; 35(1): 159-73, viii. PubMed

Ochs HD, Hagin D. Primary immunodeficiency disorders: general classification, new molecular insights, and practical approach to diagnosis and treatment. Ann Allergy Asthma Immunol. 2014; 112(6): 489-95. PubMed

Ochs HD. Patients with abnormal IgM levels: assessment, clinical interpretation, and treatment. Ann Allergy Asthma Immunol. 2008; 100(5): 509-11. PubMed

Slatter MA, Gennery AR. Clinical immunology review series: an approach to the patient with recurrent infections in childhood. Clin Exp Immunol. 2008; 152(3): 389-96. PubMed

Stiehm RE. The four most common pediatric immunodeficiencies. Adv Exp Med Biol. 2007; 601: 15-26. PubMed

van der Hilst JC H, Frenkel J. Hyperimmunoglobulin D syndrome in childhood. Curr Rheumatol Rep. 2010; 12(2): 101-7. PubMed

Yel L. Selective IgA deficiency. J Clin Immunol. 2010; 30(1): 10-6. PubMed

References from the ARUP Institute for Clinical and Experimental Pathology®

Cronin K, Escobar H, Szekeres K, Reyes-Vargas E, Rockwood AL, Lloyd MC, Delgado JC, Blanck G. Regulation of HLA-DR peptide occupancy by histone deacetylase inhibitors. Hum Vaccin Immunother. 2013; 9(4): 784-9. PubMed

Vaughn CP, Baker CL, Samowitz WS, Swensen JJ. The frequency of previously undetectable deletions involving 3' Exons of the PMS2 gene. Genes Chromosomes Cancer. 2013; 52(1): 107-12. PubMed

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Last Update: April 2016