Hypogammaglobulinemia
Hypogammaglobulinemia | |
---|---|
Specialty | Hematology |
Hypogammaglobulinemia is an immune system disorder in which not enough
Types
The following lists types of "agammaglobulinemia" catalogued in the OMIM. Hypogammaglobulinemia can have other types; see sections "Causes" and "Etymology" below.
Type | OMIM
|
Gene |
---|---|---|
AGM1 | 601495 | IGHM |
AGM2 | 613500 | IGLL1 |
AGM3 | 613501 | CD79A |
AGM4 | 613502 | BLNK
|
AGM5 | 613506 | LRRC8A |
AGM6 | 612692 | CD79B |
Symptoms and signs
The presenting feature of hypogammaglobulinemia is usually a clinical history of recurrent, chronic, or atypical infections. These infections include but are not limited to:
Babies with transient hypogammaglobulinemia (THI) usually become symptomatic 6 to 12 months after birth, with the symptoms usually consisting of frequent ear, sinus, and lung infections. Other symptoms include respiratory tract infections, food allergies, eczema, urinary tract infections, and intestinal infections.[medical citation needed]
Causes
Hypogammaglobulinemia can be caused by either a
Around 300 different genes have been identified which account for different forms of
Screening
Screening of immunoglobulin levels in relatives of CVID and IgA patients finds a familial inheritance rate of 10% to 20%. In cases where a carrier of such a mutation would like to have children, preimplantation genetic diagnosis (PGD) has been offered.[2] PGD is defined as the testing of pre-implantation stage embryos or oocytes for genetic defects. It requires in vitro fertilization, embryo biopsy, and either fluorescent in situ hybridization or polymerase chain reaction on a singular cell, making it a complex procedure. While some question the ethicality of such artificial selection, it is generally seen as an important alternative to prenatal diagnosis.[4] Prevention of secondary immunodeficiency involves monitoring patients carefully with high risk of developing hypogammaglobulinemia. This entails measuring immunoglobulin levels in patients with hematologic malignancy, or those receiving chemotherapy or immunosuppressive therapy such as rituximab.[2]
Treatment
Protocols for different forms of primary immunodeficiency vary significantly. The aim of treatments implemented by specialist centers is usually to reduce the risk of complications. One method of treatment is by
One emerging therapy is hematopoietic stem cell transplantation, which has been considered standard treatment for many combined primary immunodeficiencies including SCID, CD40 deficiency, CD40 ligand deficiency, and Wiskott-Aldrich syndrome, but has been extended to secondary immunodeficiencies over the last two decades.[5] Another emerging therapy is gene therapy, which has been used to treat X-linked SCID, SCID due to adenosine deaminase deficiency, and chronic granulomatous disease.[2]
Prognosis
Early detection and treatment of hypogammaglobulinemia is known to reduce rates of
Research
In 2015, a journal article by McDermott et al. reported on a case in which
Effect on viral evolution
One study of the genomic variation in the hepatitis C virus in patients with and without hypogammaglobulinemia found that patients with hypogammaglobulinemia had fewer nucleotide substitutions per year than the control patients, suggesting that in the absence of selective pressure caused by the immune system, the frequency of the occurrence of genetic variation in the major viral species is reduced. They used five control patients and four patients with CVID, a particularly severe form of hypogammaglobulinemia. The control patients had a mean nucleotide rate-of-change of 6.954 nucleotide substitutions per year while the patients with CVID had 0.415 nucleotide substitutions per year. While the mutations still occur in the patients with CVID, they tend to remain as a minor species in the absence of immune selection.[8]
Terminology
"Hypogammaglobulinemia" is largely synonymous with "agammaglobulinemia". When the latter term is used (as in "X-linked agammaglobulinemia") it implies that gamma globulins are not merely reduced, but completely absent. Modern assays have allowed most agammaglobulinemias to be more precisely defined as hypogammaglobulinemias,[9] but the distinction is not usually clinically relevant.
"Hypogammaglobulinemia" is distinguished from dysgammaglobulinemia, which is a reduction in some types of gamma globulins, but not others.[10]
References
- ^ "common variable immunodeficiency" at Dorland's Medical Dictionary
- ^ a b c d e f g Barmettler, Sara (14 September 2021). "Hypogammaglobulinemia: Prognosis". Epocrates. Archived from the original on 5 December 2021. Retrieved 31 May 2022.
- PMID 22035880.
- S2CID 39510284.
- PMID 25538710.
- PMID 12890430.
- PMID 25662009.
- S2CID 28147132.
- ^ "agammaglobulinemia" at Dorland's Medical Dictionary
- ^ "Dysgammaglobulinemia" at Dorland's Medical Dictionary
Further reading
- Rose, Mark E.; Lang, David M. (February 2006). "Evaluating and managing hypogammaglobulinemia". from the original on 5 December 2021. Retrieved 31 May 2022.
- Secord, Elizabeth A.; Pansare, Milind; Seth, Divya (26 December 2018). Kaliner, Michael A.; Talavera, Francisco; Simon, Michael R. (eds.). "Hypogammaglobulinemia". Allergy & Immunology. Medscape. WebMD. Archived from the original on 22 May 2022. Retrieved 31 May 2022.