# Complement deficiency

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Medical condition

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](/source/Immunodeficiency) of absent or suboptimal functioning of one of the [complement system](/source/Complement_system) proteins.[4] Because of redundancies in the [immune system](/source/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]

## Types

- Disorders of the proteins that act to ***inhibit*** the complement system (such as [C1-inhibitor](/source/C1-inhibitor)) can lead to an *overactive* response, causing conditions such as [hereditary angioedema](/source/Hereditary_angioedema).[8]

- Disorders of the proteins that act to ***activate*** the complement system (such as [C3](/source/Complement_component_3)) can lead to an *underactive* response, causing greater susceptibility to infections.[9]

## Signs and symptoms

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

- Recurring [infection](/source/Infection)

- [Auto-immune disorders](/source/Auto-immune_disorders)

- [Glomerulonephritis](/source/Glomerulonephritis)

- [Joint](/source/Joint) problems (manifestation)

- [Lung](/source/Lung) function (MBL variant alleles)

- [Angioedema](/source/Angioedema)

- [Dermatomyositis](/source/Dermatomyositis)

- [Vasculitis](/source/Vasculitis)

- [Anaphylactoid purpura](/source/Anaphylactoid_purpura)

### Complications

Neisseria, a possible complication

[Vaccinations](/source/Vaccinations) for encapsulated organisms (e.g., *[Neisseria meningitidis](/source/Neisseria_meningitidis)* and *[Streptococcus pneumoniae](/source/Streptococcus_pneumoniae)*) is crucial for preventing infections in complement deficiencies.[*[medical citation needed](https://en.wikipedia.org/wiki/Wikipedia:Identifying_reliable_sources_(medicine))*] Among the possible complications are the following:

- Deficiencies of the terminal complement components increases susceptibility to infections by *[Neisseria](/source/Neisseria)*.[11]

## 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 [autosomal](/source/Autosomal) [recessive](/source/Recessive) conditions, while [properdin deficiency](/source/Properdin_deficiency) occurs through [X-linked](/source/X-linked) inheritance. [MBL deficiency](/source/MBL_deficiency) can be inherited by either manner.[2]

### Inherited

- [Properdin deficiency](/source/Properdin_deficiency) is an [X-linked](/source/X-linked)[12] disorder that also causes susceptibility to *[Neisseria](/source/Neisseria)* infections.[2]

- C1-inhibitor deficiency or [hereditary angioedema](/source/Hereditary_angioedema) will have low C4 with normal C1 levels.[13]

### Acquired

Acquired hypocomplementemia may occur in the setting of [bone infections (osteomyelitis)](/source/Osteomyelitis), [infection of the lining of the heart (endocarditis)](/source/Endocarditis), and [cryoglobulinemia](/source/Cryoglobulinemia). [Systemic lupus erythematosus](/source/Systemic_lupus_erythematosus) is associated with low [C3](/source/Complement_component_3) and [C4](/source/Complement_component_4).[14] [Membranoproliferative glomerulonephritis](/source/Membranoproliferative_glomerulonephritis) usually has low C3.[15]

## Mechanism

Model of common structural genes and their possible contribution to the development of schizophrenia (as defined in the Sekar *et al*. article)

The mechanism of complement deficiency consists of:

- **C2**: In regard to [C2](/source/Complement_component_2) deficiency, about 5 different [mutations](/source/Mutation) in the *C2* [gene](/source/Gene) are responsible. In turn, immune function decreases and infection opportunities increase. One of the most common mutations deletes 28 DNA [nucleotides](/source/Nucleotide) from the *C2* gene. Therefore, no C2 [protein](/source/Protein) which can help make [C3-convertase](/source/C3-convertase) is produced. Ultimately, this delays/decreases immune response.[16]

- **C3**: In terms of deficiency of [C3](/source/Complement_component_3), 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.[17]

- **C4**: [C4](/source/Complement_component_4) deficiency is highly associated with [systemic lupus erythematosus](/source/Systemic_lupus_erythematosus).[3] [Aβ42](/source/Amyloid_beta), a protein involved in [Alzheimer's disease](/source/Alzheimer's_disease), can cause activation of C4 (even in plasma deficient of [C1q](/source/C1q)).[18] At least one study indicates that the genetic variation of C4 plays a role in [schizophrenia](/source/Schizophrenia).[19]

## Diagnosis

Complement tests 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]

- [CH50](/source/CH50) measurement

- [Immunochemical](/source/Immunochemistry) methods/test

- [C3](/source/Complement_component_3) deficiency screening

- [Mannose](/source/Mannose)-binding lectin (lab study)

- [Plasma](/source/Blood_plasma) levels/regulatory proteins (lab study)

## Treatment

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

[Pneumococcus](/source/Pneumococcus) and *[Haemophilus](/source/Haemophilus)* infections can be prevented via immunization.[2] [Epsilon-aminocaproic acid](/source/Epsilon-aminocaproic_acid) could be used to treat hereditary C1-INH deficiency, though the possible side effect of [intravascular](/source/Intravascular) [thrombosis](/source/Thrombosis) should be weighed.[7]

## Epidemiology

C2 deficiency has a prevalence of 1 in about 20,000 people in [Western countries](/source/Western_countries).[2]

## See also

- [Paroxysmal nocturnal hemoglobinuria](/source/Paroxysmal_nocturnal_hemoglobinuria)

## References

1. ^ [***a***](#cite_ref-osk_1-0) [***b***](#cite_ref-osk_1-1) Winkelstein, Jerry A. (2004). ["Complement Deficiencies"](https://books.google.com/books?id=I3Kh1cNJxyUC&q=complement+deficiency&pg=PA670). In Crocetti, Michael; Barone, Michael A. (eds.). *Oski's Essential Pediatrics* (2nd ed.). Philadelphia: Lippincott Williams & Wilkins. p. 670. [ISBN](/source/ISBN_(identifier)) [9780781737708](https://en.wikipedia.org/wiki/Special:BookSources/9780781737708). [Archived](https://web.archive.org/web/20230112105022/https://books.google.com/books?id=I3Kh1cNJxyUC&q=complement+deficiency&pg=PA670) from the original on 12 January 2023. Retrieved 21 September 2016.

1. ^ [***a***](#cite_ref-pat_2-0) [***b***](#cite_ref-pat_2-1) [***c***](#cite_ref-pat_2-2) [***d***](#cite_ref-pat_2-3) [***e***](#cite_ref-pat_2-4) [***f***](#cite_ref-pat_2-5) [***g***](#cite_ref-pat_2-6) ["Complement Deficiencies. What are complement deficiencies?"](https://patient.info/doctor/complement-deficiencies). *patient.info*. [Archived](https://web.archive.org/web/20171231104021/https://patient.info/doctor/complement-deficiencies) from the original on 31 December 2017. Retrieved 31 December 2017.

1. ^ [***a***](#cite_ref-scape_3-0) [***b***](#cite_ref-scape_3-1) [***c***](#cite_ref-scape_3-2) [***d***](#cite_ref-scape_3-3) [***e***](#cite_ref-scape_3-4) ["Complement Deficiencies Clinical Presentation: History, Physical, Causes"](http://emedicine.medscape.com/article/135478-clinical#showall). *emedicine.medscape.com*. [Archived](https://web.archive.org/web/20180102191532/https://emedicine.medscape.com/article/135478-clinical#showall) from the original on 2 January 2018. Retrieved 21 September 2016.

1. **[^](#cite_ref-GorbachBartlett2004_4-0)** Winkelstein, Jerry A. (2004). "The Complement System". In Gorbach, Sherwood L.; Bartlett, John G.; Blacklow, Neil R. (eds.). *Infectious Diseases*. Lippincott Williams & Wilkins. pp. 8–13. [ISBN](/source/ISBN_(identifier)) [978-0-7817-3371-7](https://en.wikipedia.org/wiki/Special:BookSources/978-0-7817-3371-7).

1. **[^](#cite_ref-5)** Sjöholm, A.G.; Jönsson, G.; Braconier, J.H.; Sturfelt, G.; Truedsson, L. (2006). "Complement deficiency and disease: An update". *Molecular Immunology*. **43** (1–2): 78–85. [doi](/source/Doi_(identifier)):[10.1016/j.molimm.2005.06.025](https://doi.org/10.1016%2Fj.molimm.2005.06.025). [PMID](/source/PMID_(identifier)) [16026838](https://pubmed.ncbi.nlm.nih.gov/16026838).

1. **[^](#cite_ref-6)** Moreland, Larry W., ed. (2004). ["Hypocomplementemia"](https://books.google.com/books?id=GiR493YLsgsC&pg=PA425). *Rheumatology and Immunology Therapy*. p. 425. [doi](/source/Doi_(identifier)):[10.1007/3-540-29662-X_1306](https://doi.org/10.1007%2F3-540-29662-X_1306). [ISBN](/source/ISBN_(identifier)) [3-540-20625-6](https://en.wikipedia.org/wiki/Special:BookSources/3-540-20625-6).

1. ^ [***a***](#cite_ref-emed_7-0) [***b***](#cite_ref-emed_7-1) *[Complement-Related Disorders](https://emedicine.medscape.com/article/136368-overview)* at [eMedicine](/source/EMedicine)

1. **[^](#cite_ref-8)** Davis, Alvin E.; Mejia, Pedro; Lu, Fengxin (1 October 2008). ["Biological activities of C1 inhibitor"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2626406). *Molecular Immunology*. **45** (16): 4057–4063. [doi](/source/Doi_(identifier)):[10.1016/j.molimm.2008.06.028](https://doi.org/10.1016%2Fj.molimm.2008.06.028). [PMC](/source/PMC_(identifier)) [2626406](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2626406). [PMID](/source/PMID_(identifier)) [18674818](https://pubmed.ncbi.nlm.nih.gov/18674818).

1. **[^](#cite_ref-9)** Ram, S.; Lewis, L. A.; Rice, P. A. (7 October 2010). ["Infections of People with Complement Deficiencies and Patients Who Have Undergone Splenectomy"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2952982). *Clinical Microbiology Reviews*. **23** (4): 740–780. [doi](/source/Doi_(identifier)):[10.1128/CMR.00048-09](https://doi.org/10.1128%2FCMR.00048-09). [PMC](/source/PMC_(identifier)) [2952982](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2952982). [PMID](/source/PMID_(identifier)) [20930072](https://pubmed.ncbi.nlm.nih.gov/20930072).

1. **[^](#cite_ref-10)** Pettigrew, H. David; Teuber, Suzanne S.; Gershwin, M. Eric (September 2009). ["Clinical Significance of Complement Deficiencies"](https://doi.org/10.1111%2Fj.1749-6632.2009.04633.x). *Annals of the New York Academy of Sciences*. **1173** (1): 108–123. [Bibcode](/source/Bibcode_(identifier)):[2009NYASA1173..108P](https://ui.adsabs.harvard.edu/abs/2009NYASA1173..108P). [doi](/source/Doi_(identifier)):[10.1111/j.1749-6632.2009.04633.x](https://doi.org/10.1111%2Fj.1749-6632.2009.04633.x). [PMID](/source/PMID_(identifier)) [19758139](https://pubmed.ncbi.nlm.nih.gov/19758139).

1. **[^](#cite_ref-11)** Aghamohammadi, Asghar; Rezaei, Nima (13 December 2012). [*Clinical Cases in Primary Immunodeficiency Diseases: A Problem-Solving Approach*](https://books.google.com/books?id=IftYOIDjQbcC&q=terminal+complement+components+Neisseria.&pg=PA334). Springer Science & Business Media. p. 334. [ISBN](/source/ISBN_(identifier)) [978-3-642-31785-9](https://en.wikipedia.org/wiki/Special:BookSources/978-3-642-31785-9). [Archived](https://web.archive.org/web/20230112105022/https://books.google.com/books?id=IftYOIDjQbcC&q=terminal+complement+components+Neisseria.&pg=PA334) from the original on 12 January 2023. Retrieved 30 January 2022.

1. **[^](#cite_ref-12)** ["OMIM Entry - # 312060 - PROPERDIN DEFICIENCY, X-LINKED; CFPD"](http://omim.org/entry/312060). *omim.org*. [Archived](https://web.archive.org/web/20191216171301/http://omim.org/entry/312060) from the original on 16 December 2019. Retrieved 21 September 2016.

1. **[^](#cite_ref-13)** Gower, Richard G; Busse, Paula J; Aygören-Pürsün, Emel; Barakat, Amin J; Caballero, Teresa; Davis-Lorton, Mark; Farkas, Henriette; Hurewitz, David S; Jacobs, Joshua S; Johnston, Douglas T; Lumry, William; Maurer, Marcus (15 February 2011). ["Hereditary Angioedema Caused By C1-Esterase Inhibitor Deficiency: A Literature-Based Analysis and Clinical Commentary on Prophylaxis Treatment Strategies"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3666183). *The World Allergy Organization Journal*. **4** (Suppl 2): S9–S21. [doi](/source/Doi_(identifier)):[10.1097/1939-4551-4-S2-S9](https://doi.org/10.1097%2F1939-4551-4-S2-S9). [PMC](/source/PMC_(identifier)) [3666183](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3666183). [PMID](/source/PMID_(identifier)) [23283143](https://pubmed.ncbi.nlm.nih.gov/23283143).

1. **[^](#cite_ref-14)** ["Systemic Lupus Erythematosus. Lupus treatment; information | Patient"](https://patient.info/doctor/systemic-lupus-erythematosus-pro). *Patient*. [Archived](https://web.archive.org/web/20190704094650/https://patient.info/doctor/Systemic-lupus-erythematosus-pro) from the original on 4 July 2019. Retrieved 21 September 2016.

1. **[^](#cite_ref-15)** ["Membranoproliferative Glomerulonephritis: Background, Pathophysiology, Etiology"](http://emedicine.medscape.com/article/240056-overview). *Medscape*. [Archived](https://web.archive.org/web/20191130165809/http://emedicine.medscape.com/article/240056-overview) from the original on 30 November 2019. Retrieved 21 September 2016.

1. **[^](#cite_ref-16)** Reference, Genetics Home. ["C2 gene"](https://medlineplus.gov/genetics/gene/c2/). *Genetics Home Reference*. [Archived](https://web.archive.org/web/20180123190642/https://ghr.nlm.nih.gov/gene/C2#conditions) from the original on 23 January 2018. Retrieved 21 September 2016.

1. **[^](#cite_ref-17)** Reference, Genetics Home. ["C3 gene"](https://medlineplus.gov/genetics/gene/c3/). *Genetics Home Reference*. [Archived](https://web.archive.org/web/20181004154129/https://ghr.nlm.nih.gov/gene/C3#conditions) from the original on 4 October 2018. Retrieved 21 September 2016.

1. **[^](#cite_ref-18)** Kolev, Martin V; Ruseva, Marieta M; Harris, Claire L; Morgan, B. Paul; Donev, Rossen M (1 March 2009). ["Implication of Complement System and its Regulators in Alzheimer's Disease"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2724661). *Current Neuropharmacology*. **7** (1): 1–8. [doi](/source/Doi_(identifier)):[10.2174/157015909787602805](https://doi.org/10.2174%2F157015909787602805). [PMC](/source/PMC_(identifier)) [2724661](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2724661). [PMID](/source/PMID_(identifier)) [19721814](https://pubmed.ncbi.nlm.nih.gov/19721814).

1. **[^](#cite_ref-19)** Sekar, Aswin; Bialas, Allison R.; de Rivera, Heather; Davis, Avery; Hammond, Timothy R.; Kamitaki, Nolan; Tooley, Katherine; Presumey, Jessy; Baum, Matthew (11 February 2016). ["Schizophrenia risk from complex variation of complement component 4"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4752392). *Nature*. **530** (7589): 177–183. [Bibcode](/source/Bibcode_(identifier)):[2016Natur.530..177.](https://ui.adsabs.harvard.edu/abs/2016Natur.530..177.). [doi](/source/Doi_(identifier)):[10.1038/nature16549](https://doi.org/10.1038%2Fnature16549). [PMC](/source/PMC_(identifier)) [4752392](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4752392). [PMID](/source/PMID_(identifier)) [26814963](https://pubmed.ncbi.nlm.nih.gov/26814963).

## Further reading

- Botto, Marina (1 January 2001). ["Links between complement deficiency and apoptosis"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC128896). *Arthritis Research & Therapy*. **3** (4): 207–210. [doi](/source/Doi_(identifier)):[10.1186/ar301](https://doi.org/10.1186%2Far301). [PMC](/source/PMC_(identifier)) [128896](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC128896). [PMID](/source/PMID_(identifier)) [11438036](https://pubmed.ncbi.nlm.nih.gov/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](/source/Doi_(identifier)):[10.1007/978-3-642-31785-9_8](https://doi.org/10.1007%2F978-3-642-31785-9_8). [ISBN](/source/ISBN_(identifier)) [978-3-642-31784-2](https://en.wikipedia.org/wiki/Special:BookSources/978-3-642-31784-2).

## External links

Classification D ICD-10: D84.1 ICD-9-CM: 279.8 OMIM: 217000 120820, 120900, 610102 DiseasesDB: 1847 External resources eMedicine: med/419 ped/447

Wikimedia Commons has media related to [Complement deficiencies](https://commons.wikimedia.org/wiki/Category:Complement_deficiencies).

[Scholia](https://www.wikidata.org/wiki/Wikidata:Scholia) has a *topic* profile for ***[Complement deficiency](https://iw.toolforge.org/scholia/topic/Q5156409)***.

v t e Lymphoid and complement disorders causing immunodeficiency Primary Antibody/humoral (B) Hypogammaglobulinemia X-linked agammaglobulinemia Transient hypogammaglobulinemia of infancy Dysgammaglobulinemia IgA deficiency IgG deficiency IgM deficiency Hyper IgM syndrome (1 2 3 4 5) Wiskott–Aldrich syndrome Hyper-IgE syndrome Other Common variable immunodeficiency ICF syndrome T cell deficiency (T) thymic hypoplasia: hypoparathyroid (Di George's syndrome) euparathyroid (Nezelof syndrome Ataxia–telangiectasia) peripheral: Purine nucleoside phosphorylase deficiency Hyper IgM syndrome (1) Severe combined (B+T) x-linked: X-SCID autosomal: Adenosine deaminase deficiency Omenn syndrome ZAP70 deficiency Bare lymphocyte syndrome Acquired HIV/AIDS Leukopenia: Lymphocytopenia Idiopathic CD4+ lymphocytopenia Complement deficiency C1-inhibitor (Angioedema/Hereditary angioedema) Complement 2 deficiency/Complement 4 deficiency MBL deficiency Properdin deficiency Complement 3 deficiency Terminal complement pathway deficiency Paroxysmal nocturnal hemoglobinuria Complement receptor deficiency

v t e Medicine Specialties and subspecialties Surgery Cardiac surgery Cardiothoracic surgery Endocrine surgery Eye surgery General surgery Colorectal surgery Digestive system surgery Hand surgery Neurosurgery Ophthalmology Oral and maxillofacial surgery Orthopedic surgery Otolaryngology ENT Pediatric surgery Plastic surgery Reproductive surgery Surgical oncology Transplant surgery Trauma surgery Urology Andrology Vascular surgery Internal medicine Allergy / Immunology Angiology Cardiology Interventional Endocrinology Gastroenterology Hepatology Geriatrics Hematology Hospital medicine Infectious diseases Nephrology Oncology Molecular oncology Pulmonology Rheumatology Obstetrics and gynaecology Gynaecology Gynecologic oncology Maternal–fetal medicine Obstetrics Reproductive endocrinology and infertility Urogynecology Diagnostic Pathology Anatomical Clinical pathology Clinical chemistry Cytopathology Medical microbiology Transfusion medicine Radiology Interventional radiology Neuroradiology Nuclear medicine Common Anesthesiology Obstetric anesthesiology Neurosurgical anesthesiology Dermatology Emergency medicine Mass gathering medicine Family medicine / General practice Hospital medicine Intensive care medicine Medical genetics Neurology Clinical neurophysiology Oral medicine Palliative care Pediatrics Neonatology Physical medicine and rehabilitation (PM&R) Preventive medicine Psychiatry Addiction psychiatry Neuropsychiatry Radiation oncology Transplantation medicine Other Addiction medicine Adolescent medicine Aviation medicine Disaster medicine Diving medicine Evolutionary medicine Expedition medicine Narcology Occupational medicine Pain management Phlebology Prison healthcare Reproductive medicine Sexual medicine Venereology Sleep medicine Sports medicine Tropical medicine Travel medicine Medical education Bachelor of Medicine, Bachelor of Surgery Bachelor of Medical Sciences Doctor of Medicine Doctor of Osteopathic Medicine Master of Medicine Master of Surgery Medical school Medical student MD–PhD Medical Scientist Training Program Related topics Allied health History of medicine Medical terminology Nanomedicine Personalized medicine Public health Rural health Therapy Veterinary medicine Physician Category Commons Wikiproject Portal Outline

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Adapted from the Wikipedia article [Complement deficiency](https://en.wikipedia.org/wiki/Complement_deficiency) by Wikipedia contributors ([contributor history](https://en.wikipedia.org/wiki/Complement_deficiency?action=history)). Available under [Creative Commons Attribution-ShareAlike 4.0 International](https://creativecommons.org/licenses/by-sa/4.0/). Changes may have been made.