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 animmunodeficiency of absent or suboptimal functioning of one of thecomplement system proteins.^[4] Because of redundancies in theimmune 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] whilesecondary complement disorder means decreased complement levels that are not directly due to a genetic cause but secondary to another medical condition.^[7]

• Disorders of the proteins that act toinhibit the complement system (such asC1-inhibitor) can lead to anoveractive response, causing conditions such ashereditary angioedema.^[8]
• Disorders of the proteins that act toactivate the complement system (such asC3) can lead to anunderactive response, causing greater susceptibility to infections.^[9]

The following symptoms (signs) are consistent with complement deficiency in general:^[1][3][10]

Vaccinations for encapsulated organisms (e.g.,Neisseria meningitidis andStreptococcus 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 byNeisseria.^[11]

The cause of complement deficiency is genetics (though cases of an acquired nature do exist post infection). The majority of complement deficiencies are inherited asautosomalrecessive conditions, whileproperdin deficiency occurs throughX-linked inheritance.MBL deficiency can be inherited by either manner.^[2]

• Properdin deficiency is anX-linked^[12] disorder that also causes susceptibility toNeisseria infections.^[2]
• C1-inhibitor deficiency orhereditary angioedema will have low C4 with normal C1 levels.^[13]

Acquired hypocomplementemia may occur in the setting ofbone infections (osteomyelitis),infection of the lining of the heart (endocarditis), andcryoglobulinemia.Systemic lupus erythematosus is associated with lowC3 andC4.^[14]Membranoproliferative glomerulonephritis usually has low C3.^[15]

The mechanism of complement deficiency consists of:

• C2: In regard toC2 deficiency, about 5 differentmutations in theC2gene are responsible. In turn, immune function decreases and infection opportunities increase. One of the most common mutations deletes 28 DNAnucleotides from theC2 gene. Therefore, no C2protein which can help makeC3-convertase is produced. Ultimately, this delays/decreases immune response.^[16]
• C3: In terms of deficiency ofC3, it has been found that 17 mutations in theC3 gene cause problems with C3. This rare condition mutates or prevents C3 protein from forming, lowering the immune system's ability to protect.^[17]
• C4:C4 deficiency is highly associated withsystemic lupus erythematosus.^[3]Aβ42, a protein involved inAlzheimer's disease, can cause activation of C4 (even in plasma deficient ofC1q).^[18] At least one study indicates that the genetic variation of C4 plays a role inschizophrenia.^[19]

The diagnostic tests used to diagnose a complement deficiency include:^[3]

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

In terms of management for complement deficiency,immunosuppressive therapy should be used depending on the disease presented. AC1-INH concentrate can be used for angio-oedema (C1-INH deficiency).^[2][3]

Pneumococcus andHaemophilus infections can be prevented via immunization.^[2]Epsilon-aminocaproic acid could be used to treat hereditary C1-INH deficiency, though the possible side effect ofintravascularthrombosis should be weighed.^[7]

C2 deficiency has a prevalence of 1 in about 20,000 people inWestern countries.^[2]

• Paroxysmal nocturnal hemoglobinuria

• Botto, Marina (1 January 2001)."Links between complement deficiency and apoptosis".Arthritis Research & Therapy.3 (4):207–210.doi:10.1186/ar301.PMC 128896.PMID 11438036.
• Sullivan, Kathleen; Eibl, Martha M.; Erdős, Melinda; Maródi, László; Wolf, Hermann M.; Mahmoudi, Maryam; Rezaei, Nima (2012). "Complement Deficiencies".Clinical Cases in Primary Immunodeficiency Diseases. pp. 325–341.doi:10.1007/978-3-642-31785-9_8.ISBN 978-3-642-31784-2.

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• Complement deficiency
• Noninfectious immunodeficiency-related cutaneous conditions
• Syndromes

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