Transient Hypogammaglobulinemia of Infancy Workup

  • Author: Alan P Knutsen, MD; Chief Editor: Harumi Jyonouchi, MD   more...
 
Updated: Mar 26, 2012
 

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.

Memory and switched B cells should be analyzed. CD19+/CD27+ memory B cells and IgM-IgD-CD27+ switched B cells are decreased in many of the B-cell immunodeficiencies, such as CVID, HIGM syndrome, and selective antibody deficiency (SAD). Note the following:

  • Bukowska-Strakova et al analyzed memory and switched B cells in CVID, THI and selective IgA deficiency (SIgAD).[15] Memory and switched B cells were typically decreased in 56 children with CVID but normal in 37 children with THI and in 39 children with SIgAD compared to age-matched control children age 0-7 years. However, they did observe in some children younger than 5 years with symptomatic THI, decreased memory, and switched B cells.
  • Moschese et al[16, 17] reported decreased CD27+ memory B cells and decreased IgM-IgD-CD27+ switched B cells in children with THI older than 2 years. The investigators postulated that these children may have a permanent immunodeficiency later in life.
  • In the authors’ experience, in infants with THI and decreased antibody responses to either conjugated and/or Spneumoniae immunizations, memory and switched B cells are typically decreased. However, memory and switched B cells normalize when IgG and antibody responses improve.

The phenotype of decreased IgG and decreased specific antibody deficiency has been associated with mutations of CD20, CD21, and CD81.[18, 19, 20] 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.

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Contributor Information and Disclosures
Author

Alan P Knutsen, MD  Professor of Pediatrics, Director of Pediatric Allergy and Immunology, Director Jeffrey Modell Diagnostic & Research Center for Primary Immuodeficiences (CGCMC), 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, American College of Allergy, Asthma and Immunology, and Clinical Immunology Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

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.

David Pallares, MD  Clinical Assistant Professor, Department of Pediatrics, Division of Allergy and Immunology, University of Louisville School of Medicine

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, Division of Pulmonary, Allergy/Immunology, and Infectious Diseases, Department of Pediatrics, University of Medicine and Dentistry of New Jersey-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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