Complement deficiency
| Complement deficiency | |
|---|---|
 | |
| Complement pathway (normal) | |
| Specialty | Hematology  |
| Symptoms | Recurring infection, rheumatic disease[1] |
| Causes | Can be inherited or acquired[2] |
| Diagnostic method | CH50 measurement, Plasma level[3] |
| Treatment | Immunosuppressive therapy[2] |
Complement deficiency is an immunodeficiency of absent or suboptimal functioning of one of the complement system proteins.[4] Because of redundancies in the immune system, many complement disorders are never diagnosed. Some studies estimate that less than 10% are identified.[5] Hypocomplementemia may be used more generally to refer to decreased complement levels,[6] while secondary complement disorder means decreased complement levels that are not directly due to a genetic cause but secondary to another medical condition.[7]
Signs and symptoms
The following symptoms (signs) are consistent with complement deficiency in general:[1][3][8]
- Recurring infection
- Auto-immune disorders
- Glomerulonephritis
- Joint problems (manifestation)
- Lung function (MBL variant alleles)
- Angioedema
- Dermatomyositis
- Vasculitis
- Anaphylactoid purpura
Complications
Vaccinations for encapsulated organisms (e.g., Neisseria meningitidis and Streptococcus pneumoniae) is crucial for preventing infections in complement deficiencies.[medical citation needed
] Among the possible complications are the following:
- Deficiencies of the terminal complement components increases susceptibility to infections by Neisseria.[9]
Causes
The cause of complement deficiency is genetics (though cases of an acquired nature do exist post infection). The majority of complement deficiencies are inherited as
X-linked inheritance. MBL deficiency can be inherited by either manner.[2]
Inherited
- C1-inhibitor deficiency or hereditary angioedema will have low C4 with normal C1 levels.[11]
Acquired
Acquired hypocomplementemia may occur in the setting of
Systemic lupus erythematosus is associated with low C3 and C4.[12] Membranoproliferative glomerulonephritis usually has low C3.[13]
Mechanism
The mechanism of complement deficiency consists of:
- C2: In regard to C2 deficiency, about 5 different mutations in the C2 gene are responsible. In turn, immune function decreases and infection opportunities increase. One of the most common mutations deletes 28 DNA nucleotides from the C2 gene. Therefore, no C2 protein which can help make C3-convertase is produced. Ultimately, this delays/decreases immune response.[14]
- C3: In terms of deficiency of C3, it has been found that 17 mutations in the C3 gene cause problems with C3. This rare condition mutates or prevents C3 protein from forming, lowering the immune system's ability to protect.[15]
- C4: C1q).[16] At least one study indicates that the genetic variation of C4 plays a role in schizophrenia.[17]
Diagnosis
| C4 (C) | FB (A) | C3 | CH50 | Conditions |
|---|---|---|---|---|
| · | ↓ | ↓ | ↓ | PSG, C3 NeF AA
|
| ↓ | · | ↓ | · | HAE, C4D |
| · | · | · | ↓ | TCPD |
| ↓ | ·/↓ | ↓ | ↓ | SLE
|
| ↑ | ↑ | ↑ | ↑ | inflammation |
The diagnostic tests used to diagnose a complement deficiency include:[3]
- CH50measurement
- Immunochemical methods/test
- C3 deficiency screening
- Mannose-binding lectin (lab study)
- Plasma levels/regulatory proteins (lab study)
Types
- Disorders of the proteins that act to inhibit the complement system (such as C1-inhibitor) can lead to an overactive response, causing conditions such as hereditary angioedema.[18]
- Disorders of the proteins that act to activate the complement system (such as C3) can lead to an underactive response, causing greater susceptibility to infections.[19]
Treatment
In terms of management for complement deficiency,
intravascular thrombosis should be weighed.[7]
Epidemiology
C2 deficiency has a prevalence of 1 in about 20,000 people in
Western countries.[2]
See also
References
- ^ ISBN 9780781737708. Retrieved 21 September 2016.
- ^ a b c d e f g "Complement Deficiencies. What are complement deficiencies?". patient.info. Retrieved 31 December 2017.
- ^ a b c d e "Complement Deficiencies Clinical Presentation: History, Physical, Causes". emedicine.medscape.com. Retrieved 21 September 2016.
- ISBN 978-0-7817-3371-7.
- PMID 16026838. – via ScienceDirect(Subscription may be required or content may be available in libraries.)
- ISBN 9783540206255. Retrieved 30 August 2016.
- ^ a b Complement-Related Disorders at eMedicine
- PMID 19758139.
- ISBN 978-3-642-31785-9. Retrieved 30 January 2022.
- ^ "OMIM Entry - # 312060 - PROPERDIN DEFICIENCY, X-LINKED; CFPD". omim.org. Retrieved 21 September 2016.
- PMID 23283143.
- ^ "Systemic Lupus Erythematosus. Lupus treatment; information | Patient". Patient. Retrieved 21 September 2016.
- ^ "Membranoproliferative Glomerulonephritis: Background, Pathophysiology, Etiology". Medscape. Retrieved 21 September 2016.
- ^ Reference, Genetics Home. "C2 gene". Genetics Home Reference. Retrieved 21 September 2016.
- ^ Reference, Genetics Home. "C3 gene". Genetics Home Reference. Retrieved 21 September 2016.
- PMID 19721814.
- PMID 26814963.
- PMID 18674818.
- PMID 20930072.
Further reading
- Botto, Marina (1 January 2001). "Links between complement deficiency and apoptosis". Arthritis Research & Therapy. 3 (4): 207–210. PMID 11438036.
- Aghamohammadi, Asghar; Rezaei, Nima (2012). Clinical cases in primary immunodeficiency diseases a problem-solving approach. Berlin: Springer. ISBN 9783642317859. Retrieved 21 September 2016.
External links
Scholia has a topic profile for Complement deficiency.
