B cell defects results in humoral immune deficiencies(1-3).Some of the defects that result in defective B cell signaling can lead to selective or generalized hypogammaglobulinemia, even in the presence of normal numbers of B cells.

IgA deficiency (IgAD) is the most common primary immunodeficiency. The prevalence in Caucasians is one in 500. Most individuals with IgA deficiency are clinically asymptomatic. Those with symptoms of immunodeficiency have mainly sinopulmonary or gastrointestinal infections. Associated deficiency of IgG2, IgG4 or specific antibody may result in more severe infections(4). IgAD is associated also with autoimmune phenomena (5).

Among those with defects in early B-cell development, Approximately 85% have X-linked agammaglobulinemia (XLA), a disorder caused by mutations in the cytoplasmic enzyme, Bruton's tyrosine kinase (Btk) (2,6). Patients are typically infants or young male children with recurrent, severe bacterial infections(7).

Transient hypogammaglobulinemia of infancy (THI) is a primary humoral immunodeficiency characterized by a transient lack of IgG. Treatment with IVIG as an alternative to antibiotic prophylaxis remains controversial also in symptomatic children(8). During follow-up, immunoglobulin levels of infants with THI tend to normalize at the age between 12 - 48 months(9).

Failure to properly receive T-cell signals can lead to hyper-IgM syndrome(10). In addition to susceptibility to recurrent and opportunistic infections, these patients are prone to autoimmune manifestations, especially hematologic abnormalities, arthritis, and inflammatory bowel disease(11).

Common variable immunodeficiency (CVID) is the most common clinically significant primary immune defect. CVID is characterized by hypogammaglobulinemia, but due to the intrinsic dysregulation of the immune system there are also defects in T-cell activation and proliferation, as well as dendritic cell and cytokine defects. Up to 80% of patients have recurrent sinopulmonary infections, but autoimmunity (mainly immune thrombocytopenic purpura and hemolytic anemia) and inflammatory complications are also common(12,13).

1. Vale AM, Schroeder HW, Jr. Clinical consequences of defects in B-cell development. J Allergy Clin Immunol 2010;125:778-787.

2. Mohamed AJ, Yu L, Backesjo CM, Vargas L, Faryal R, Aints A et al. Bruton's tyrosine kinase (Btk): function, regulation, and transformation with special emphasis on the PH domain. Immunol Rev 2009;228:58-73.

3. Moise A, Nedelcu FD, Toader MA, Sora SM, Tica A, Ferastraoaru DE et al. Primary immunodeficiencies of the B lymphocyte. J Med Life 2010;3:60-63.

4. Latiff AH, Kerr MA. The clinical significance of immunoglobulin A deficiency. Ann Clin Biochem 2007;44:131-139.

5. Jacob CM, Pastorino AC, Fahl K, Carneiro-Sampaio M, Monteiro RC. Autoimmunity in IgA deficiency: revisiting the role of IgA as a silent housekeeper. J Clin Immunol 2008;28 Suppl 1:S56-S61.

6. Conley ME, Broides A, Hernandez-Trujillo V, Howard V, Kanegane H, Miyawaki T et al. Genetic analysis of patients with defects in early B-cell development. Immunol Rev 2005;203:216-234.

7. Stewart DM, Lian L, Nelson DL. The clinical spectrum of Bruton's agammaglobulinemia. Curr Allergy Asthma Rep 2001;1:558-565.

8. Duse M, Iacobini M, Leonardi L, Smacchia P, Antonetti L, Giancane G. Transient hypogammaglobulinemia of infancy: intravenous immunoglobulin as first line therapy. Int J Immunopathol Pharmacol 2010;23:349-353.

9. Qian JH, Zhu JX, Zhu XD, Chen TX. Clinical features and follow-up of Chinese patients with symptomatic hypogammaglobulinemia in infancy. Chin Med J (Engl ) 2009;122:1877-1883.

10. Ochs HD. Patients with abnormal IgM levels: assessment, clinical interpretation, and treatment. Ann Allergy Asthma Immunol 2008;100:509-511.

11. Jesus AA, Duarte AJ, Oliveira JB. Autoimmunity in hyper-IgM syndrome. J Clin Immunol 2008;28 Suppl 1:S62-S66.

12. Agarwal S, Cunningham-Rundles C. Autoimmunity in common variable immunodeficiency. Curr Allergy Asthma Rep 2009;9:347-352.

13. Deane S, Selmi C, Naguwa SM, Teuber SS, Gershwin ME. Common variable immunodeficiency: etiological and treatment issues. Int Arch Allergy Immunol 2009;150:311-324.