Agammaglobulinemia, primary
Summary
Characterized by the attack of antibodies known as gammaglobulins (responsible for defending the body from infection), leaving those affected very susceptible to illnesses, which then progress aggressively and are more likely to prove deadly. Subtypes include the more common Bruton agammaglobulinemia, which is linked to the male X gene and thus found exclusively in males, and the autosomal recessive type, only occasionally affecting females.
(Global Autoimmune Institute, 2023)
Agammaglobulinemia is an immune disorder related to antibody deficiency (hypogammaglobulinemia) and is manifested in a variety of immune deficiency disorders in which the immune system is compromised. This group of immune deficiencies may be the consequence of an inherited condition, an impaired immune system from known or unknown cause, a relation to autoimmune diseases, or a malignancy.
Immunoglobulin deficiencies may be referred to by many different names, as there are several variables within the separate but related immune disorders; and there are also many subgroups. Antibody deficiency, immunoglobulin deficiency, and gamma globulin deficiency are all synonyms for hypogammaglobulinemia…
X-linked agammaglobulinemia (a-gam-uh-glob-u-lih-NEE-me-uh) — also called XLA — is an inherited (genetic) immune system disorder that reduces your ability to fight infections. People with XLA might get infections of the inner ear, sinuses, respiratory tract, bloodstream and internal organs.
XLA affects males almost exclusively, although females can be genetic carriers of the condition. Most people with XLA are diagnosed in infancy or early childhood, after they've had repeated infections. Some people aren't diagnosed until adulthood.
(Autoimmune Association, 2022)
Symptoms
Babies with XLA generally appear healthy for the first few months because they're protected by the antibodies they got from their mothers before birth. When these antibodies clear from their systems, the babies begin to develop often severe, recurrent bacterial infections — such as of the ears, lungs, sinuses and skin — that can be life-threating.
Male infants born with XLA have:
Very small tonsils
Small or no lymph nodes
(Autoimmune Association, 2022)
Serial bacterial infections (including frequent bronchitis episodes), chronic diarrhea, conjunctivitis, otitis media, pneumonia, sinusitis, skin infections, and upper respiratory tract infections.
(Global Autoimmune Institute, 2023)
Diagnostic Criteria
Under Investigation
Diagnostic Tests
Under Investigation
Human Leukocyte Antigen (HLA) Associations
Under Investigation
Genetic Associations
LRBA Deficiency
Lipopolysaccharide (LPS)-responsive beige-like anchor (LRBA) deficiency is one of the monogenic causes of polyautoimmunity (Azizi et al, 2018).
Monogenic: mono=one and genic=gene. Monogenic means that it involves or is controlled by a single gene.
I have included LRBA deficiency here because neither the Autoimmune Association, nor the Global Autoimmune Institute, list this particular genetic disease as an autoimmune disorder, but it clearly has autoimmune and polyautoimmune associations. In one study, hypogammaglobulinemia was found in 57% of patients with LPS-responsive beige-like anchor deficiency (Gámez-Díaz et al, 2016). Autoimmune cytopenias are also a common autoimmune manifestation of this disorder.
The following information, from the National Institutes of Health gene database, describes the LRBA gene function and the consequences of defects:
The protein encoded by this gene is a member of the WDL-BEACH-WD (WBW) gene family. Its expression is induced in B cells and macrophages by bacterial lipopolysaccharides (LPS). The encoded protein associates with protein kinase A and may be involved in leading intracellular vesicles to activated receptor complexes, which aids in the secretion and/or membrane deposition of immune effector molecules. Defects in this gene are associated with the disorder common variable immunodeficiency-8 with autoimmunity. Two transcript variants encoding different isoforms have been found for this gene.
(National Institutes of Health, 2023)
Tissue-Type or Cell-Type Attacked
Under Investigation
Attacking Immune Cell Type or Process
Under Investigation
Treatment Modality
Under Investigation
Managing Specialist(s)
Under Investigation
Associated Infections
Under Investigation
Associated Toxins
Under Investigation
Research Authors
Under Investigation
Research Institutions
Under Investigation
Average Time from Symptom Onset to Diagnosis
Under Investigation
Last Updated
January 16, 2023
References
Aggamaglobulinemia. Autoimmune Association. (2022, November 10). Retrieved January 02, 2023 from https://autoimmune.org/disease-information/agammaglobulinemia/
Aggamaglobulinemia, Primary. Global Autoimmune Institute. (2023). Retrieved January 02, 2023 from https://www.autoimmuneinstitute.org/agammaglobulinemia/
Azizi G, Abolhassani H, Zaki-Dizaji M, Habibi S, Mohammadi H, Shaghaghi M, Yazdani R, Anaya JM, Rezaei N, Hammarström L, Aghamohammadi A. Polyautoimmunity in Patients with LPS-Responsive Beige-Like Anchor (LRBA) Deficiency. Immunol Invest. 2018 Jul;47(5):457-467. doi: 10.1080/08820139.2018.1446978. Epub 2018 Mar 12. PMID: 29528757.
Gámez-Díaz L, August D, Stepensky P, Revel-Vilk S, Seidel MG, Noriko M, Morio T, Worth AJJ, Blessing J, Van de Veerdonk F, Feuchtinger T, Kanariou M, Schmitt-Graeff A, Jung S, Seneviratne S, Burns S, Belohradsky BH, Rezaei N, Bakhtiar S, Speckmann C, Jordan M, Grimbacher B. The extended phenotype of LPS-responsive beige-like anchor protein (LRBA) deficiency. J Allergy Clin Immunol. 2016 Jan;137(1):223-230. doi: 10.1016/j.jaci.2015.09.025. PMID: 26768763.
LRBA LPS responsive beige-like anchor protein. National Institutes of Health, National Library of Medicine, National Center for Biotechnology Information. (2023, January 08). Retrieved January 16, 2023, from https://www.ncbi.nlm.nih.gov/gene/26191