eMedicine Specialties > Pediatrics: General Medicine > Allergy & Immunology

Transient Hypogammaglobulinemia of Infancy: Differential Diagnoses & Workup

Author: Alan P Knutsen, MD, Professor of Pediatrics, Allergy and Immunology, Director of Pediatric Clinical Immunology Laboratory, Department of Pathology, St Louis University Health Sciences Center
Contributor Information and Disclosures

Updated: Jun 20, 2008

Differential Diagnoses

Agammaglobulinemia
Bruton Agammaglobulinemia
Common Variable Immunodeficiency
IgA and IgG Subclass Deficiencies
Protein-Losing Enteropathy
Severe Combined Immunodeficiency

Other Problems to Be Considered

X-linked agammaglobulinemia
B-linked agammaglobulinemia
Hyper-IgM syndrome
Selective IgA deficiency
Antibody deficiency with normal serum immunoglobulins
Secondary immunodeficiency due to loss of IgG and IgA

Workup

Laboratory Studies

  • In evaluating transient hypergammaglobulinemia of infancy (THI), serum IgG levels are decreased less than 2 SDs for age-adjusted reference range levels. Often, serum IgA levels are also decreased; however, IgM levels are typically within the reference range. Flow cytometry studies reveal that the percentages and numbers of CD3+ and especially CD4+ T cells may be slightly decreased but are typically normal. T-cell function assessed by delayed type hypersensitivity (DTH) and in vitro lymphoproliferative responses are normal. Percentages and numbers of CD19+ B cells may be increased; however, in the author's experience, CD27+ memory and CD27+IgD-IgM- switched B cells may be decreased.
  • Antibody titers to protein immunizations (eg, tetanus toxoid, diphtheria toxoid, polio) are at normal or near-normal concentrations. This distinguishes THI from more serious B- and T-cell immunodeficiency disorders. However, antibody responses to viral respiratory infections may also be decreased. Furthermore, Dalal and Roifman (2001) reported that antibody responses following immunization may be normal but may not persist on serial determinations.6
  • In contrast to responses to protein antigens, antibody responses to polysaccharide antigens are often abnormal. In children with THI older than 2 years, Wolpert and Knutsen (1998) observed poor antibody responses to the unconjugated pneumococcal vaccine (Pneumovax); in children with THI younger than 2 years, poor antibody response to the conjugated-pneumococcal vaccine (Prevnar) was observed.11 Dorsey et al (2006) reported that immunizations to conjugated polysaccharide antigens are often subnormal in children with THI.1  These authors observed decreased antibody responses to both conjugated H influenzae type B vaccine and S pneumoniae immunization in children with THI.
  • The serum immunoglobulin pattern of decreased IgG and IgA levels resembles X-linked hyper-IgM (XL-HIGM type 1) syndrome, autosomal recessive CD40 deficiency HIGM (type 2), and common variable immunodeficiency. In HIGM and common variable immunodeficiency, mature B cells are present. In addition, memory and switched B cells are decreased in these conditions, which may be seen in THI as well. However, a severe antibody deficiency distinguishes these conditions from THI. Deficiency of T-cell CD40 ligand (gp39, CD154) is the genetic defect in XL-HIGM, and deficiency of B-cell CD40 is the genetic defect in HIGM type 3. CD40L and CD40 can be analyzed using flow cytometry.
  • Deficiency of activation-induced cytidine deaminase (AID) and uracil-DNA glycosylase (UNG) in B cells has been associated with autosomal recessive forms of HIGM that affect B cells (HIGM type 2). Gene analysis of these defects in HIGM can be analyzed by commercial laboratories that specialize in genetic defects.

More on Transient Hypogammaglobulinemia of Infancy

Overview: Transient Hypogammaglobulinemia of Infancy
Differential Diagnoses & Workup: Transient Hypogammaglobulinemia of Infancy
Treatment & Medication: Transient Hypogammaglobulinemia of Infancy
Follow-up: Transient Hypogammaglobulinemia of Infancy
References
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References

  1. Dorsey MJ, Orange JS. Impaired specific antibody response and increased B-cell population in transient hypogammaglobulinemia of infancy. Ann Allergy Asthma Immunol. Nov 2006;97(5):590-5. [Medline].

  2. Siegel RL, Issekutz T, Schwaber J, et al. Deficiency of T helper cells in transient hypogammaglobulinemia of infancy. N Engl J Med. Nov 26 1981;305(22):1307-13. [Medline].

  3. Dalal I, Reid B, Nisbet-Brown E, Roifman CM. The outcome of patients with hypogammaglobulinemia in infancy and early childhood. J Pediatr. Jul 1998;133(1):144-6. [Medline].

  4. Cano F, Mayo DR, Ballow M. Absent specific viral antibodies in patients with transient hypogammaglobulinemia of infancy. J Allergy Clin Immunol. Feb 1990;85(2):510-3. [Medline].

  5. Kowalczyk D, Mytar B, Zembala M. Cytokine production in transient hypogammaglobulinemia and isolated IgA deficiency. J Allergy Clin Immunol. Oct 1997;100(4):556-62. [Medline].

  6. Dalal I, Roifman CM. Hypogammaglobulinemia of infancy. Immunol Allergy Clin North Am. 2001;21:129-39.

  7. Tiller TL, Buckley RH. Transient hypogammaglobulinemia of infancy: review of the literature, clinical and immunologic features of 11 new cases, and long-term follow-up. J Pediatr. Mar 1978;92(3):347-53. [Medline].

  8. Walker AM, Kemp AS, Hill DJ, Shelton MJ. Features of transient hypogammaglobulinaemia in infants screened for immunological abnormalities. Arch Dis Child. Mar 1994;70(3):183-6. [Medline].

  9. Dressler F, Peter HH, Muller W, Rieger CH. Transient hypogammaglobulinemia of infancy: Five new cases, review of the literature and redefinition. Acta Paediatr Scand. Sep 1989;78(5):767-74. [Medline].

  10. Hayakawa H, Iwata T, Yata J, Kobayashi N. Primary immunodeficiency syndrome in Japan. I. Overview of a nationwide survey on primary immunodeficiency syndrome. J Clin Immunol. Jan 1981;1(1):31-9. [Medline].

  11. Wolpert J, Knutsen AP. Natural history of selective antibody deficiency to bacterial polysaccharide antigens in children. Pediatr Asthma, Allergy, Immunol. 1998;12:183-191.

  12. Hsueh KC, Chiu HH, Lin HC, et al. Transient hypogammaglobulinemia of infancy presenting as Staphylococcus aureus sepsis with deep neck infection. J Microbiol Immunol Infect. Apr 2005;38(2):141-4. [Medline].

  13. Sorensen RU, Leiva LE, Giangrosso PA, et al. Response to a heptavalent conjugate Streptococcus pneumoniae vaccine in children with recurrent infections who are unresponsive to the polysaccharide vaccine. Pediatr Infect Dis J. Aug 1998;17(8):685-91. [Medline].

  14. Castigli E, Wilson SA, Scott S, et al. TACI and BAFF-R mediate isotype switching in B cells. J Exp Med. Jan 3 2005;201(1):35-9. [Medline].

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  17. Kowalczyk D, Baran J, Webster AD, Zembala M. Intracellular cytokine production by Th1/Th2 lymphocytes and monocytes of children with symptomatic transient hypogammaglobulinaemia of infancy (THI) and selective IgA deficiency (SIgAD). Clin Exp Immunol. Mar 2002;127(3):507-12. [Medline].

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  20. Oxelius VA. IgG subclass pattern in primary immunodeficiency disorders. Monogr Allergy. 1986;19:156-63. [Medline].

  21. Salzer U, Maul-Pavicic A, Cunningham-Rundles C, et al. ICOS deficiency in patients with common variable immunodeficiency. Clin Immunol. Dec 2004;113(3):234-40. [Medline].

  22. Sneller MC. Common variable immunodeficiency. Am J Med Sci. Jan 2001;321(1):42-8. [Medline].

  23. Sneller MC, Strober W, Eisenstein E, et al. NIH conference. New insights into common variable immunodeficiency. Ann Intern Med. May 1 1993;118(9):720-30. [Medline].

  24. Whelan MA, Hwan WH, Beausoleil J, et al. Infants presenting with recurrent infections and low immunoglobulins: characteristics and analysis of normalization. J Clin Immunol. Jan 2006;26(1):7-11. [Medline].

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Further Reading

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Keywords

transient hypogammaglobulinemia of infancy, THI, decreased immunoglobulin A, IgA, decreased immunoglobulin G, IgG, immunoglobulin M, IgM, common variable immunodeficiency, CVID, Bruton's agammaglobulinemia, hyper-IgM syndrome, HIGM, B-cell defect, dysgammaglobulinemia, upper respiratory tract infections, otitis media, sinusitis, pneumonia, severe combined immunodeficiency, SCID, bronchial infections, polysaccharide-encapsulated bacteria, varicella, oral candidiasis, sepsis, meningitis, food allergy, asthma, allergic rhinitis, acute lymphocytic leukemia, ALL, X-linked infantile agammaglobulinemia

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Contributor Information and Disclosures

Author

Alan P Knutsen, MD, Professor of Pediatrics, Allergy and Immunology, Director of Pediatric Clinical Immunology Laboratory, Department of Pathology, St Louis University Health Sciences Center
Alan P Knutsen, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology and Clinical Immunology Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine.com, Inc
Disclosure: Pfizer Inc Stock Investment from broker recommendation; Avanir Pharma Stock Investment from broker recommendation

Managing Editor

David J Valacer, MD, Consulting Staff, Hoffman La Roche Pharmaceuticals
David J Valacer, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Academy of Pediatrics, American Association for the Advancement of Science, American Thoracic Society, and New York Academy of Sciences
Disclosure: Nothing to disclose.

CME Editor

David Pallares, MD, Clinical Assistant Professor, Department of Pediatrics, Division of Allergy and Immunology, University of Louisville
David Pallares, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology
Disclosure: Nothing to disclose.

Chief Editor

Harumi Jyonouchi, MD, Associate Professor, Department of Pediatrics, Division of Pulmonary Allergy/Immunology and Infectious Diseases, UMDNJ-New Jersey Medical School
Harumi Jyonouchi, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Academy of Pediatrics, American Association of Immunologists, American Medical Association, Clinical Immunology Society, New York Academy of Sciences, Society for Experimental Biology and Medicine, Society for Mucosal Immunology, and Society for Pediatric Research
Disclosure: Nothing to disclose.

 
 
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