Chapter 101 : Primary Antibody Deficiency Diseases

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In recent years several rare autosomal recessive disorders that result in antibody deficiency have been reported. Some antibody deficiencies are part of a more broadly expressed systemic disorder or part of an immunodeficiency that affects T cells and/or NK cells as well as B cells. The possibility of immunodeficiency should be considered in any patient who is hospitalized for a major infection requiring intravenous therapy. Most patients with X-linked agammaglobulinemia (XLA) develop recurrent or persistent infections in the first 4 to 8 months of life, and the majority are recognized to have immunodeficiency at less than 3 years of age. Defects in μ heavy chain account for about one-third of the patients with autosomal recessive agammaglobulinemia. Mutation detection is the most practical way of making a definitive diagnosis. Single gene defects of the immune system may have features in common with common variable immunodeficiency (CVID). Recent studies suggest that analysis of B-cell phenotype may be useful in identifying patients with CVID who have more severe disease. Either whole blood or density gradient-separated mononuclear cells can be used to examine lymphocyte cell surface markers. A variety of techniques can be used to provide mutation detection. The advantages and disadvantages of some techniques are listed in this chapter. A detailed history of past infections, a careful family history, and a physical examination that focuses on sites typically involved in antibody deficiencies should come before any laboratory tests.

Citation: Conley M. 2006. Primary Antibody Deficiency Diseases, p 906-913. In Detrick B, Hamilton R, Folds J (ed), Manual of Molecular and Clinical Laboratory Immunology, 7th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815905.ch101
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Fluorescence-activated cell sorter analysis of B cells from a patient with XLA. Density gradient-separated peripheral blood mononuclear cells from a control (top panels) and a patient with XLA (bottom panels) were stained with PE-CD19 and either FITC-CD3 (left panels) or FITC-polyclonal antihuman IgM (right panels). The dot plot shows approximately 20,000 gated events from the control sample and 200,000 events from the patient sample. The control sample contains 7.3% CD19+ cells, and the patient sample contains 0.07% CD19+ cells. Note that the intensity of CD19 staining is homogeneous in the control sample but variable in the patient sample. Additionally, the majority of the B cells from the patient are very brightly stained for surface IgM, whereas those from the control are variable in surface IgM expression.

Citation: Conley M. 2006. Primary Antibody Deficiency Diseases, p 906-913. In Detrick B, Hamilton R, Folds J (ed), Manual of Molecular and Clinical Laboratory Immunology, 7th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815905.ch101
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Image of FIGURE 2

SSCP analysis of DNA from a patient with XLA and his family members. Exon 17 of Btk was amplified using primers that flank the coding sequence and splice sites. The PCR products were denatured in heat and then allowed to rena-ture as they migrated through an electrophoresis gel. Lanes 1, 2, 6, and 7 contain DNA from controls. The DNA sample in lane 5 is from a patient with XLA. DNA samples from the patient’s mother and sister are in lanes 3 and 4, respectively.

Citation: Conley M. 2006. Primary Antibody Deficiency Diseases, p 906-913. In Detrick B, Hamilton R, Folds J (ed), Manual of Molecular and Clinical Laboratory Immunology, 7th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815905.ch101
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Citation: Conley M. 2006. Primary Antibody Deficiency Diseases, p 906-913. In Detrick B, Hamilton R, Folds J (ed), Manual of Molecular and Clinical Laboratory Immunology, 7th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815905.ch101
Generic image for table

Citation: Conley M. 2006. Primary Antibody Deficiency Diseases, p 906-913. In Detrick B, Hamilton R, Folds J (ed), Manual of Molecular and Clinical Laboratory Immunology, 7th Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815905.ch101

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