Complement deficiency

Complement deficiency
Complement pathway (normal)
Classification and external resources
Specialty	hematology
ICD-10	D84.1
ICD-9-CM	279.8
OMIM	217000 120820, 120900, 610102
DiseasesDB	1847 1869 , 1873 , 7384 , 34381
eMedicine	med/419 ped/447

Complement deficiency is an immunodeficiency of absent or suboptimal functioning of one of the complement system proteins.^[1] Because there are redundancies in the immune system, many complement disorders are never diagnosed, some studies estimated that less than 10% are identified.^[2]Hypocomplementemia may be used more generally to refer to decreased complement levels^[3] while secondary complement disorder is to low complement levels that are not directly due to a genetic cause but secondary to another medical condition.^[4]

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^[5]
• 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.^[6]

Signs/symptoms

The following symptoms (signs) are consistent with complement deficiency in general:^[7][8][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 autosomal recessive, while properdin deficiency could be X-linked inheritance, and finally MBL deficiency can be both ^[10]

Complications

Neisseria, a possible complication

Vaccinations for encapsulated organisms is crucial for preventing infections in complement deficiencies. Among the possible complications are the following:

• Deficiencies of the terminal complement components increases susceptibility to infections by Neisseria.^[11]
• Properdin deficiency is an X-linked ^[12] disorder that also causes susceptibility to Neisseria infections.^[10]
• C1-inhibitor deficiency or hereditary angioedema will have low C4 with normal C1 levels.^[13]
• Systemic lupus erythematosus is associated with low C3 and C4^[14]
• Membranoproliferative glomerulonephritis usually has low C3.^[15]

Mechanism

C4 role in Schizophrenia

The mechanism of complement deficiency consists of:

• C2 -in regards to complement component 2 deficiency, about 5 different mutations in the C2 gene are responsible for it.In turn immune function decreases and infection opportunities rise. One of the most common mutations deletes 28 DNA nucleotides from C2 gene. Therefore no C2 protein is made which would help make convertase C3. Ultimately this delays/decreases immune response.^[16]

• C3 -in terms of complement deficiency in C3 it has been found that 17 mutations in C3 gene cause problems with complement component 3. This rare condition's mutations creates prevent cells, consequently the immune system ability to protect decreases.^[17]
• C4 -C4 deficiency has a very high percent association with systemic lupus erythematosus ^[18] C4 role in Alzheimer's disease is from Kolev et al, brain inflammation may have a role in Alzheimer's disease pathogenesis.Aβ42 can cause activation of C4,whats more Aβ can activate C4 in plasma (deficient of C1q)^[19] A recent study indicates that a variation of C4 has a role in schizophrenia.^[20]

Diagnosis

Among the diagnostic tests that can be done in determining if an individual has complement deficiencies is:^[7][18]

• CH50 measurement
• Immunochemical methods/test
• C3 deficiency screening
• Mannose-binding lectin (lab study)
• Plasma levels/regulatory proteins (lab study)

Treatment

In terms of management for complement deficiency, immunosuppressive therapy should be used depending on the disease presented. A C1-INH concentrate can be used for angio-oedema (C1-INH deficiency).^[7][10]

Pneumococcus and haemophilus infections prevention can be taken via immunization for those with complement deficiency.^[10] Epsilon-aminocaproic acid could be used to treat hereditary C1-INH deficiency, though the possible side effect of intravascular thrombosis should be weighed.^[4]

Epidemiology

In terms of the epidemiology of complement deficiency one finds that C2 deficiency for example, is prevalent in 120,000 people in Western countries,^[10] it occurs in about 1 in 10,000 persons.^[21]

See also

• Paroxysmal nocturnal hemoglobinuria

References

Further reading

• Botto, Marina (1 January 2001). "Links between complement deficiency and apoptosis". Arthritis Research & Therapy. 3: 207. doi:10.1186/ar301. ISSN 1478-6362. Retrieved 31 August 2016. 
• Aghamohammadi, Asghar; Rezaei, Nima (2012). Clinical cases in primary immunodeficiency diseases a problem-solving approach. Berlin: Springer. ISBN 9783642317859. Retrieved 21 September 2016.