Agammaglobulinemias

Definition:

There are three major categories of antibody deficiencies: (a) defects in early B cell development, (b) hyper-IgM syndromes (also called class switch recombination defects), and (c) common variable immunodeficiency (CVID). Category (a) consists of agammaglobulinaemias (AGM). Defects in early B cell development are characterized by the onset of recurrent bacterial infections in the first 5 years of life, profound hypogammaglobulinemia, markedly reduced or absent B cells in the peripheral circulation, and (in the bone marrow) a severe block in B cell differentiation before the production of surface immunoglobulin-positive B cells. Mutations in Btk, the gene responsible for X-linked agammaglobulinemia (XLA), account for approximately 85% of affected patients. Approximately half of the remaining patients have mutations in genes encoding components of the pre-B cell receptor (pre-BCR) or BCR, including mu heavy chain (IGHM); the signal transduction molecules Ig-alpha (CD79A) and Ig-beta (CD79B); and lambda 5 (IGLL1), which forms the surrogate light chain with Vpre-B. A small number of patients with defects in BLNK, a scaffold protein that assembles signal transduction molecules activated by cross-linking of the BCR, have been reported.

References:

[1]. A Kerry Dobbs, et al. Cutting edge: a hypomorphic mutation in Igbeta (CD79b) in a patient with immunodeficiency and a leaky defect in B cell development. J Immunol. 2007 Aug 15;179(4):2055-9. [Content Brief]

[2]. Akihisa Sawada, et al. A congenital mutation of the novel gene LRRC8 causes agammaglobulinemia in humans. J Clin Invest. 2003 Dec;112(11):1707-13. [Content Brief]

[3]. Baerbel Keller, et al. Germline deletion of CIN85 in humans with X chromosome-linked antibody deficiency. J Exp Med. 2018 May 7;215(5):1327-1336. [Content Brief]

[4]. Bertrand Boisson, et al. A recurrent dominant negative E47 mutation causes agammaglobulinemia and BCR(-) B cells. J Clin Invest. 2013 Nov;123(11):4781-5. [Content Brief]

[5]. Carole Le Coz, et al. Constrained chromatin accessibility in PU.1-mutated agammaglobulinemia patients. J Exp Med. 2021 Jul 5;218(7):e20201750. [Content Brief]

[6]. Chantal Lagresle-Peyrou, et al. The BLNK adaptor protein has a nonredundant role in human B-cell differentiation. J Allergy Clin Immunol. 2014 Jul;134(1):145-54. [Content Brief]

[7]. Consuelo Anzilotti, et al. An essential role for the Zn2+ transporter ZIP7 in B cell development. Nat Immunol. 2019 Mar;20(3):350-361. [Content Brief]

[8]. L Yel, et al. Mutations in the mu heavy-chain gene in patients with agammaglobulinemia. N Engl J Med. 1996 Nov 14;335(20):1486-93. [Content Brief]

[9]. Mary Ellen Conley, et al. Agammaglobulinemia and absent B lineage cells in a patient lacking the p85α subunit of PI3K. J Exp Med. 2012 Mar 12;209(3):463-70. [Content Brief]

[10]. Mary Ellen Conley, et al. Primary B cell immunodeficiencies: comparisons and contrasts. Annu Rev Immunol. 2009;27:199-227. [Content Brief]

[11]. Massimo Morra, et al. Genetic diagnosis of primary immune deficiencies. Immunol Allergy Clin North Am. 2008 May;28(2):387-412, x. [Content Brief]

[12]. Shanshan Gao, et al. Clinical characteristics and prenatal diagnosis for 22 families in Henan Province of China with X-linked agammaglobulinemia (XLA) related to Bruton's tyrosine kinase (BTK) gene mutations. BMC Med Genet. 2020 Jun 17;21(1):131. [Content Brief]

[13]. Y Minegishi, et al. Mutations in Igalpha (CD79a) result in a complete block in B-cell development. J Clin Invest. 1999 Oct;104(8):1115-21. [Content Brief]

[14]. Y Minegishi, et al. Mutations in the human lambda5/14.1 gene result in B cell deficiency and agammaglobulinemia. J Exp Med. 1998 Jan 5;187(1):71-7. [Content Brief]

Biomedical Dictionary

The Biomedical Dictionary is a comprehensive and professional collection of biological academic terms and subject datas. All explanations are supported by authoritative books or high impact factor literatures, and you can acquire accurate explanations of the biomedical terms you want to know.

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z #

Name
Email *

	Sorry, but the email address you supplied was invalid.