Immunoglobulin D Deficiency 

  • Author: Donald A Dibbern Jr, MD; Chief Editor: Michael A Kaliner, MD   more...
 
Updated: Jul 22, 2011
 

Background

Immunoglobulin D (IgD) deficiency is a defect of humoral immunity that is characterized by abnormally low serum levels of IgD immunoglobulins. Little is known about the normal function of IgD, and few clinical signs or symptoms are associated with its absence. Individuals with low or absent levels of IgD do not appear unusually predisposed to infections.

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Pathophysiology

Genetic rearrangements occur during the maturation of B lymphocytes, eventually resulting in the surface expression of both immunoglobulin M (IgM) and IgD on mature B cells. Cell signaling occurs through this surface IgD. IgD production by B cells is stimulated by interleukin (IL)–4 and IL-10.[1]

The physiologic purpose of free serum IgD is not well understood, though it may fine tune or modulate humoral immune response.[2] In mice, IgD may substitute for some functions of IgM when IgM is absent. Studies in IgM-deficient IgM-/- mice reveal that B cells with surface expression of IgM were replaced by B cells with surface expression of IgD. Immunization of IgM-/- mice revealed an IgD immune response in place of the now absent IgM response, although with a delayed increase in antibody concentration as compared to normal.[3] Recent studies have suggested that IgD-only B cells may play a significant role in immune responses to superantigens.[4] Investigations into the evolutionary origins of IgD are also ongoing.[5, 6, 7, 8]

Low serum IgD levels are not distributed in a normal gaussian fashion.[9, 10] IgD deficiency is associated with the specific human leukocyte antigens HLA-B18, F1C30, and DR3 in a Spanish Basque population[11] and HLA-B8, SC01, DR3 in white subjects in an American study.[12] A 2008 report noted that depletion of circulating IgD+ memory B cells occurs in pediatric HIV infection, despite control of viral load with highly active anti-retroviral therapy (HAART).[13]

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Epidemiology

Frequency

United States

One report indicates that approximately 11% of 371 American Red Cross blood donors and 6% of 1529 study subjects had low or undetectable IgD levels (< 0.002 mg/mL). In the study group, a number of the individuals with low IgD had rheumatologic disease (eg, juvenile rheumatoid arthritis, lupus, psoriatic arthritis, vasculitis), but the frequency of low IgD within groups of patients with each disease did not differ from the normal controls using chi-square analysis.[10] In another study, using a cutoff of 2.15 IU/mL, assays of 245 healthy adults and 301 healthy children revealed that approximately 13% of each group had low levels of IgD.[9]

Mortality/Morbidity

Low or undetectable levels of IgD, in the absence of other concurrent disease or immune defects (eg, common variable immunodeficiency, complement deficiency), are not associated with morbidity or increased mortality. Specifically, patients with low or undetectable IgD levels do not demonstrate an increased incidence of infections of any type.[14]

Sex

Overall levels of serum IgD are higher in males than females,[15] but specific incidence of abnormally low IgD is approximately equal between the sexes.[9]

Age

Children younger than 3 years, both with and without an immunodeficiency, appear to have an increased prevalence of low IgD levels.[16, 17, 18] After infancy, age is not associated with increased prevalence of low IgD levels.[9]

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Contributor Information and Disclosures
Author

Donald A Dibbern Jr, MD  Consulting Staff (Allergist), Providence St Vincent Medical Center

Donald A Dibbern Jr, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Allergy Asthma and Immunology, and Oregon Medical Association

Disclosure: Nothing to disclose.

Coauthor(s)

John M Routes, MD  Professor of Pediatrics, Medicine, Microbiology and Molecular Genetics, Chief, Section of Allergy and Clinical Immunology, Department of Pediatrics, Medical College of Wisconsin

John M Routes, MD, is a member of the following medical societies: Alpha Omega Alpha, American Academy of Allergy Asthma and Immunology, American Association of Immunologists, American College of Allergy, Asthma and Immunology, American Society for Microbiology, American Society for Virology, Clinical Immunology Society, and Federation of American Societies for Experimental Biology

Disclosure: Nothing to disclose.

Specialty Editor Board

Melvin Berger, MD, PhD  Adjunct Professor of Pediatrics and Pathology, Case Western Reserve University; Senior Medical Director, Clinical Research and Development, CSL Behring, LLC

Melvin Berger, MD, PhD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Allergy Asthma and Immunology, American Academy of Pediatrics, American Association of Immunologists, American Pediatric Society, American Society for Clinical Investigation, and Clinical Immunology Society

Disclosure: CSL Behring Salary Employment; CSL Behring Ownership interest Employment; America's Health insurance plans Consulting fee Subject Matter Expert For Clinical Immunization Safety Assessment Network acvtivity of CDC

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Michael R Simon, MD, MA  Clinical Professor Emeritus, Departments of Internal Medicine and Pediatrics, Wayne State University School of Medicine; Adjunct Staff, Division of Allergy and Immunology, Department of Internal Medicine, William Beaumont Hospital

Michael R Simon, MD, MA is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American College of Allergy, Asthma and Immunology, American College of Physicians, American Federation for Medical Research, Michigan Allergy and Asthma Society, Michigan State Medical Society, Royal College of Physicians and Surgeons of Canada, and Society for Experimental Biology and Medicine

Disclosure: Secretory IgA, Inc. Ownership interest Management position

Timothy D Rice, MD  Associate Professor, Departments of Internal Medicine and Pediatrics and Adolescent Medicine, St Louis University School of Medicine

Timothy D Rice, MD is a member of the following medical societies: American Academy of Pediatrics and American College of Physicians

Disclosure: Nothing to disclose.

Chief Editor

Michael A Kaliner, MD  Clinical Professor of Medicine, George Washington University School of Medicine; Chief, Section of Allergy and Immunology, Washington Hospital Center; Medical Director, Institute for Asthma and Allergy

Michael A Kaliner, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Association of Immunologists, American College of Allergy, Asthma and Immunology, American Society for Clinical Investigation, American Thoracic Society, and Association of American Physicians

Disclosure: Alcon Consulting fee Consulting; Greer Consulting fee Consulting; Sanofi Consulting fee Consulting; Schering/Merck Consulting fee Consulting; Teva Consulting fee Consulting; Meda Honoraria Speaking and teaching; Ista Consulting

References

  1. Levan-Petit I, Lelievre E, Barra A, et al. Th2 cytokine dependence of IgD production by normal human B cells. Int Immunol. 1999;11:1819-1828.

  2. Geisberger R, Lamers M, Achatz G. The riddle of the dual expression of IgM and IgD. Immunology. Aug 2006;118(4):429-37. [Medline].

  3. Lutz C, Ledermann B, Kosco-Vilbois MH, et al. IgD can largely substitute for loss of IgM function in B cells. Nature. 1998;393 (6687):797-801.

  4. Seifert M, Steimle-Grauer SA, Goossens T, Hansmann ML, Brauninger A, Kuppers R. A model for the development of human IgD-only B cells: Genotypic analyses suggest their generation in superantigen driven immune responses. Mol Immunol. Feb 2009;46(4):630-9. [Medline].

  5. Gambon-Deza F, Espinel CS. IgD in the reptile leopard gecko. Mol Immunol. Jul 2008;45(12):3470-6. [Medline].

  6. Chen K, Xu W, Wilson M, et al. Immunoglobulin D enhances immune surveillance by activating antimicrobial, proinflammatory and B cell-stimulating programs in basophils. Nat Immunol. Aug 2009;10(8):889-98. [Medline]. [Full Text].

  7. Chen K, Cerutti A. New insights into the enigma of immunoglobulin D. Immunol Rev. Sep 2010;237(1):160-79. [Medline]. [Full Text].

  8. Chen K, Cerutti A. The function and regulation of immunoglobulin D. Curr Opin Immunol. Jun 2011;23(3):345-52. [Medline]. [Full Text].

  9. Dunnette SL, Gleich GJ, Weinshilboum RM. Inheritance of low serum immunoglobulin D. J Clin Invest. Aug 1978;62(2):248-55. [Medline].

  10. Fraser PA, Schur PH. Hypoimmunoglobulinemia D: frequency, family studies, and association with HLA. Clin Immunol Immunopathol. Apr 1981;19(1):67-74. [Medline].

  11. Calvo B, Castano L, Marcus-Bagley D, et al. The [HLA-B18, F1C30, DR3] conserved extended haplotype carries a susceptibility gene for IgD deficiency. J Clin Immunol. May 2000;20(3):216-20. [Medline].

  12. Alper CA, Marcus-Bagley D, Awdeh Z, et al. Prospective analysis suggests susceptibility genes for deficiencies of IgA and several other immunoglobulins on the [HLA-B8, SC01, DR3] conserved extended haplotype. Tissue Antigens. Sep 2000;56(3):207-16. [Medline].

  13. Jacobsen MC, Thiebaut R, Fisher C, Sefe D, Clapson M, Klein N. Pediatric human immunodeficiency virus infection and circulating IgD+ memory B cells. J Infect Dis. Aug 15 2008;198(4):481-5. [Medline].

  14. Sanal O, Ersoy F, Tezcan I, et al. Serum IgD concentrations in immunodeficiency diseases. Turk J Pediatr. Jul-Sep 1990;32(3):175-82. [Medline].

  15. Mosedale DE, Sandhu MS, Luan J, Goodall M, Grainger DJ. A new sensitive and specific enzyme-linked immunosorbent assay for IgD. J Immunol Methods. 2006;313(1-2):74-80. [Medline].

  16. Litzman J, Ward AM, Wild G, et al. Serum IgD levels in children under investigation for and with defined immunodeficiency. Int Arch Allergy Immunol. Sep 1997;114(1):54-8. [Medline].

  17. Haraldsson A, Weemaes CM, Jonasdottir S, et al. Serum immunoglobulin D in infants and children. Scand J Immunol. Apr 2000;51(4):415-8. [Medline].

  18. Josephs SH, Buckley RH. Serum IgD concentrations in normal infants, children, and adults and in patients with elevated IgE. J Pediatr. Mar 1980;96(3 Pt 1):417-20. [Medline].

  19. Buckley RH, Fiscus SA. Serum IgD and IgE concentrations in immunodeficiency diseases. J Clin Invest. Jan 1975;55(1):157-65. [Medline].

  20. de Laat PC, Weemaes CM, Bakkeren JA. Immunoglobulin levels during follow-up of children with selective IgA deficiency. Scand J Immunol. Jun 1992;35(6):719-25. [Medline].

  21. Alper CA, Xu J, Cosmopoulos K, et al. Immunoglobulin deficiencies and susceptibility to infection among homozygotes and heterozygotes for C2 deficiency. J Clin Immunol. Jul 2003;23(4):297-305. [Medline].

  22. Lee SK, Metrakos JD, Tanaka KR, et al. Genetic influence on serum IgD levels. Pediatr Res. Jan 1980;14(1):60-3. [Medline].

  23. Levan-Petit I, Cardonna J, Garcia M, et al. Sensitive ELISA for human immunoglobulin D measurement in neonate, infant, and adult sera. Clin Chem. Jun 2000;46(6 Pt 1):876-8. [Medline].

  24. Vladutiu AO. Immunoglobulin D: properties, measurement, and clinical relevance. Clin Diagn Lab Immunol. Mar 2000;7(2):131-40. [Medline].

  25. Vladutiu AO, Netto D. Is quantitation of serum IgD clinically useful? [letter]. Clin Chem. Jun 1982;28(6):1409-10. [Medline].

 
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