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Primary humoral immunodeficiencies: An overview

Francisco A Bonilla, MD, PhD
Section Editor
E Richard Stiehm, MD
Deputy Editor
Elizabeth TePas, MD, MS


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 immunodeficiencies, the severe combined immunodeficiencies, and disorders resulting from phagocytic and complement defects.

The symptoms, signs, and molecular pathophysiology of the major humoral immunodeficiencies 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 immunodeficiencies 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".)


Humoral immunodeficiency 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 [1]. 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) [2]. 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 [3]. 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 [4]. Chronic diarrhea is seen in both children and adults [5]. Autoimmune disease is occasionally the presenting feature in adults. Primary humoral immunodeficiency should also be considered in patients with nodular lymphoid hyperplasia in the gut or unexplained hepatosplenomegaly.


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Literature review current through: Oct 2015. | This topic last updated: Nov 23, 2015.
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  1. Notarangelo L, Casanova JL, Fischer A, et al. Primary immunodeficiency diseases: an update. J Allergy Clin Immunol 2004; 114:677.
  2. Ballow M. Primary immunodeficiency disorders: antibody deficiency. J Allergy Clin Immunol 2002; 109:581.
  3. 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.
  4. 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.
  5. Agarwal S, Mayer L. Pathogenesis and treatment of gastrointestinal disease in antibody deficiency syndromes. J Allergy Clin Immunol 2009; 124:658.
  6. Farr M, Struthers GR, Scott DG, Bacon PA. Fenclofenac-induced selective IgA deficiency in rheumatoid arthritis. Br J Rheumatol 1985; 24:367.
  7. Guillemin F, Bene MC, Aussedat R, et al. Hypogammaglobulinemia associated with gold therapy: evidence for a partial maturation blockade of B cells. J Rheumatol 1987; 14:1034.
  8. Lee AH, Levinson AI, Schumacher HR Jr. Hypogammaglobulinemia and rheumatic disease. Semin Arthritis Rheum 1993; 22:252.
  9. Williams A, Scott DL, Greenwood A, Huskisson EC. The clinical value of measuring immunoglobulins when assessing penicillamine therapy in rheumatoid arthritis. Clin Rheumatol 1988; 7:347.
  10. Knight AK, Cunningham-Rundles C. Oxcarbazepine-induced immunoglobulin deficiency. Clin Diagn Lab Immunol 2005; 12:560.
  11. Okumura A, Tsuge I, Kamachi Y, et al. Transient hypogammaglobulinemia after antiepileptic drug hypersensitivity. Pediatr Neurol 2007; 36:342.
  12. Abe S, Suzuki T, Hori T, et al. Hypogammaglobulinemia during antipsychotic therapy. Psychiatry Clin Neurosci 1998; 52:115.
  13. Azar AE, Ballas ZK. Reversible panhypogammaglobulinemia associated with the antiepileptic agent levetiracetam. Ann Allergy Asthma Immunol 2008; 101:108.
  14. Hayman G, Bansal A. Antibody deficiency associated with carbamazepine. BMJ 2002; 325:1213.
  15. Joubert PH, Aucamp AK, Potgieter GM, Verster F. Epilepsy and IgA deficiency--the effect of sodium valproate. S Afr Med J 1977; 52:642.
  16. Maeoka Y, Hara T, Dejima S, Takeshita K. IgA and IgG2 deficiency associated with zonisamide therapy: a case report. Epilepsia 1997; 38:611.
  17. Pereira LF, Sanchez JF. Reversible panhypogammaglobulinemia associated with phenytoin treatment. Scand J Infect Dis 2002; 34:785.
  18. Rice CM, Johnston SL, Unsworth DJ, et al. Recurrent herpes simplex virus encephalitis secondary to carbamazepine induced hypogammaglobulinaemia. J Neurol Neurosurg Psychiatry 2007; 78:1011.
  19. 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.
  20. 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.
  21. 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.
  22. www.correlagen.com (Accessed on February 11, 2010).
  23. 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.
  24. 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.