Primary humoral immune deficiencies: An overview
- Francisco A Bonilla, MD, PhD
Francisco A Bonilla, MD, PhD
- Associate Professor of Pediatrics
- Harvard Medical School
The term primary immunodeficiency disease denotes disorders resulting from the mostly inherited defects of the immune system. Multiple isolated defects and combined disorders have been described, including humoral immune deficiencies, the severe combined immunodeficiencies, and disorders resulting from phagocytic and complement defects.
The symptoms, signs, and molecular pathophysiology of the major humoral immune deficiencies will be reviewed here, as well as pertinent aspects of the laboratory evaluation and differential diagnosis. An overview of the laboratory abnormalities observed in the different primary humoral immune deficiencies is presented in the table (table 1). General considerations and descriptions of methods used in the evaluation of immune system function are discussed separately. (See "Laboratory evaluation of the immune system".)
PRESENTATION OF HUMORAL IMMUNE DEFICIENCY
Humoral immune deficiency refers to diseases resulting from impaired antibody production, because of either a molecular defect intrinsic to B cells or a failure of interactions between B and T cells . Cellular immunity is largely intact, in contrast to diseases classified as combined immunodeficiencies, despite underlying T cell defects in some of these diseases. (See "Combined immunodeficiencies" and "Severe combined immunodeficiency (SCID): An overview".)
Antibody deficiency characteristically leads to recurrent, often severe, upper and lower respiratory tract infections with encapsulated bacteria (eg, Streptococcus pneumoniae, Haemophilus influenzae) . Children commonly present with recurrent otitis media, sinusitis, and pneumonia. The same is true of adults, although otitis media is less common. Viral infections of the respiratory tract also occur with greater frequency and severity in these patients . Additional infectious diseases may be associated with particular syndromes. (See "Acute otitis media in children: Epidemiology, microbiology, clinical manifestations, and complications", section on 'Risk factors'.)
Common associated findings in children include poor growth and failure to thrive, recurrent fevers, and poor school attendance and performance . Chronic diarrhea is seen in both children and adults . Autoimmune disease is occasionally the presenting feature in adults. Primary humoral immune deficiency should also be considered in patients with nodular lymphoid hyperplasia in the gut or unexplained hepatosplenomegaly.
- Notarangelo L, Casanova JL, Fischer A, et al. Primary immunodeficiency diseases: an update. J Allergy Clin Immunol 2004; 114:677.
- Ballow M. Primary immunodeficiency disorders: antibody deficiency. J Allergy Clin Immunol 2002; 109:581.
- Kainulainen L, Vuorinen T, Rantakokko-Jalava K, et al. Recurrent and persistent respiratory tract viral infections in patients with primary hypogammaglobulinemia. J Allergy Clin Immunol 2010; 126:120.
- Wood P, Stanworth S, Burton J, et al. Recognition, clinical diagnosis and management of patients with primary antibody deficiencies: a systematic review. Clin Exp Immunol 2007; 149:410.
- Agarwal S, Mayer L. Pathogenesis and treatment of gastrointestinal disease in antibody deficiency syndromes. J Allergy Clin Immunol 2009; 124:658.
- Revy P, Muto T, Levy Y, et al. Activation-induced cytidine deaminase (AID) deficiency causes the autosomal recessive form of the Hyper-IgM syndrome (HIGM2). Cell 2000; 102:565.
- Imai K, Slupphaug G, Lee WI, et al. Human uracil-DNA glycosylase deficiency associated with profoundly impaired immunoglobulin class-switch recombination. Nat Immunol 2003; 4:1023.
- Quartier P, Bustamante J, Sanal O, et al. Clinical, immunologic and genetic analysis of 29 patients with autosomal recessive hyper-IgM syndrome due to Activation-Induced Cytidine Deaminase deficiency. Clin Immunol 2004; 110:22.
- www.correlagen.com (Accessed on February 11, 2010).
- Hennig C, Baumann U, Ilginus C, et al. Successful treatment of autoimmune and lymphoproliferative complications of patients with intrinsic B-cell immunodeficiencies with Rituximab. Br J Haematol 2010; 148:445.
- Karaca NE, Durandy A, Gulez N, et al. Study of patients with Hyper-IgM type IV phenotype who recovered spontaneously during late childhood and review of the literature. Eur J Pediatr 2011; 170:1039.
- PRESENTATION OF HUMORAL IMMUNE DEFICIENCY
- DIFFERENTIAL DIAGNOSIS
- X-LINKED AGAMMAGLOBULINEMIA
- AUTOSOMAL RECESSIVE AGAMMAGLOBULINEMIAS
- HYPERIMMUNOGLOBULIN M SYNDROMES
- Clinical manifestations
- Laboratory findings
- COMMON VARIABLE IMMUNODEFICIENCY
- TRANSIENT HYPOGAMMAGLOBULINEMIA OF INFANCY
- OTHER ANTIBODY DEFECTS
- IgA deficiency
- Specific antibody deficiency
- IgG subclass deficiency
- Selective IgM deficiency
- Selective IgE deficiency
- Hyperimmunoglobulin-D syndrome