Complement deficiency

• 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.{{Cite journal |last=Davis |first=Alvin E. |last2=Mejia |first2=Pedro |last3=Lu |first3=Fengxin |date=1 October 2008 |title=Biological activities of C1 inhibitor |journal=Molecular Immunology |volume=45 |issue=16 |pages=4057–4063 |doi=10.1016/j.molimm.2008.06.028 |pmc=2626406 |pmid=18674818 }}
• 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.{{Cite journal |last=Ram |first=S. |last2=Lewis |first2=L. A. |last3=Rice |first3=P. A. |date=7 October 2010 |title=Infections of People with Complement Deficiencies and Patients Who Have Undergone Splenectomy |journal=Clinical Microbiology Reviews |volume=23 |issue=4 |pages=740–780 |doi=10.1128/CMR.00048-09 |pmc=2952982 |pmid=20930072 }}

The following symptoms (signs) are consistent with complement deficiency in general:{{Cite book |last=Winkelstein |first=Jerry A. |title=Oski's Essential Pediatrics |date=2004 |publisher=Lippincott Williams & Wilkins |isbn=9780781737708 |editor-last=Crocetti |editor-first=Michael |edition=2nd |location=Philadelphia |page=670 |language=en |chapter=Complement Deficiencies |access-date=21 September 2016 |editor-last2=Barone |editor-first2=Michael A. |chapter-url=https://books.google.com/books?id=I3Kh1cNJxyUC&q=complement+deficiency&pg=PA670 |archive-url=https://web.archive.org/web/20230112105022/https://books.google.com/books?id=I3Kh1cNJxyUC&q=complement+deficiency&pg=PA670 |archive-date=12 January 2023 |url-status=live}}{{Cite journal |last=Pettigrew |first=H. David |last2=Teuber |first2=Suzanne S. |last3=Gershwin |first3=M. Eric |date=September 2009 |title=Clinical Significance of Complement Deficiencies |journal=Annals of the New York Academy of Sciences |volume=1173 |issue=1 |pages=108–123 |bibcode=2009NYASA1173..108P |doi=10.1111/j.1749-6632.2009.04633.x |pmid=19758139 |doi-access=free }}

{{columns-list|colwidth=30em|

• Recurring infection
• Auto-immune disorders
• Glomerulonephritis
• Joint problems (manifestation)
• Lung function (MBL variant alleles)
• Angioedema
• Dermatomyositis
• Vasculitis
• Anaphylactoid purpura

}}

File:Neisseria-meningitidis-Differentially-Controls-Host-Cell-Motility-through-PilC1-and-PilC2-pone.0006834.s003.ogv

Vaccinations for encapsulated organisms (e.g., Neisseria meningitidis and Streptococcus pneumoniae) is crucial for preventing infections in complement deficiencies.{{medical citation needed|date=September 2016}} Among the possible complications are the following:

• Deficiencies of the terminal complement components increases susceptibility to infections by Neisseria.{{Cite book |last=Aghamohammadi |first=Asghar |url=https://books.google.com/books?id=IftYOIDjQbcC&q=terminal+complement+components+Neisseria.&pg=PA334 |title=Clinical Cases in Primary Immunodeficiency Diseases: A Problem-Solving Approach |last2=Rezaei |first2=Nima |date=13 December 2012 |publisher=Springer Science & Business Media |isbn=978-3-642-31785-9 |page=334 |language=en |access-date=30 January 2022 |archive-url=https://web.archive.org/web/20230112105022/https://books.google.com/books?id=IftYOIDjQbcC&q=terminal+complement+components+Neisseria.&pg=PA334 |archive-date=12 January 2023 |url-status=live}}

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 recessive conditions, while properdin deficiency occurs through X-linked inheritance. MBL deficiency can be inherited by either manner.

• Properdin deficiency is an X-linked{{Cite web |title=OMIM Entry - # 312060 - PROPERDIN DEFICIENCY, X-LINKED; CFPD |url=http://omim.org/entry/312060 |url-status=live |archive-url=https://web.archive.org/web/20191216171301/http://omim.org/entry/312060 |archive-date=16 December 2019 |access-date=21 September 2016 |website=omim.org}} disorder that also causes susceptibility to Neisseria infections.
• C1-inhibitor deficiency or hereditary angioedema will have low C4 with normal C1 levels.{{Cite journal |last=Gower |first=Richard G |last2=Busse |first2=Paula J |last3=Aygören-Pürsün |first3=Emel |last4=Barakat |first4=Amin J |last5=Caballero |first5=Teresa |last6=Davis-Lorton |first6=Mark |last7=Farkas |first7=Henriette |last8=Hurewitz |first8=David S |last9=Jacobs |first9=Joshua S |last10=Johnston |first10=Douglas T |last11=Lumry |first11=William |last12=Maurer |first12=Marcus |date=15 February 2011 |title=Hereditary Angioedema Caused By C1-Esterase Inhibitor Deficiency: A Literature-Based Analysis and Clinical Commentary on Prophylaxis Treatment Strategies |journal=The World Allergy Organization Journal |volume=4 |issue=Suppl 2 |pages=S9–S21 |doi=10.1097/1939-4551-4-S2-S9 |pmc=3666183 |pmid=23283143 }}

Acquired hypocomplementemia may occur in the setting of bone infections (osteomyelitis), infection of the lining of the heart (endocarditis), and cryoglobulinemia. Systemic lupus erythematosus is associated with low C3 and C4.{{Cite web |title=Systemic Lupus Erythematosus. Lupus treatment; information {{!}} Patient |url=http://patient.info/doctor/systemic-lupus-erythematosus-pro |url-status=live |archive-url=https://web.archive.org/web/20190704094650/https://patient.info/doctor/Systemic-lupus-erythematosus-pro |archive-date=4 July 2019 |access-date=21 September 2016 |website=Patient}} Membranoproliferative glomerulonephritis usually has low C3.{{Cite web |title=Membranoproliferative Glomerulonephritis: Background, Pathophysiology, Etiology |url=http://emedicine.medscape.com/article/240056-overview |url-status=live |archive-url=https://web.archive.org/web/20191130165809/http://emedicine.medscape.com/article/240056-overview |archive-date=30 November 2019 |access-date=21 September 2016 |website=Medscape}}

File:Genetic Risk of Schizophrenia Summary Figure.png

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.{{Cite web |last=Reference |first=Genetics Home |title=C2 gene |url=https://ghr.nlm.nih.gov/gene/C2#conditions |url-status=live |archive-url=https://web.archive.org/web/20180123190642/https://ghr.nlm.nih.gov/gene/C2#conditions |archive-date=23 January 2018 |access-date=21 September 2016 |website=Genetics Home Reference}}
• 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.{{Cite web |last=Reference |first=Genetics Home |title=C3 gene |url=https://ghr.nlm.nih.gov/gene/C3#conditions |url-status=live |archive-url=https://web.archive.org/web/20181004154129/https://ghr.nlm.nih.gov/gene/C3#conditions |archive-date=4 October 2018 |access-date=21 September 2016 |website=Genetics Home Reference}}
• C4: C4 deficiency is highly associated with systemic lupus erythematosus. Aβ42, a protein involved in Alzheimer's disease, can cause activation of C4 (even in plasma deficient of C1q).{{Cite journal |last=Kolev |first=Martin V |last2=Ruseva |first2=Marieta M |last3=Harris |first3=Claire L |last4=Morgan |first4=B. Paul |last5=Donev |first5=Rossen M |date=1 March 2009 |title=Implication of Complement System and its Regulators in Alzheimer's Disease |journal=Current Neuropharmacology |volume=7 |issue=1 |pages=1–8 |doi=10.2174/157015909787602805 |pmc=2724661 |pmid=19721814 }} At least one study indicates that the genetic variation of C4 plays a role in schizophrenia.{{Cite journal |last=Sekar |first=Aswin |last2=Bialas |first2=Allison R. |last3=de Rivera |first3=Heather |last4=Davis |first4=Avery |last5=Hammond |first5=Timothy R. |last6=Kamitaki |first6=Nolan |last7=Tooley |first7=Katherine |last8=Presumey |first8=Jessy |last9=Baum |first9=Matthew |date=2016-02-11 |title=Schizophrenia risk from complex variation of complement component 4 |journal=Nature |volume=530 |issue=7589 |pages=177–183 |bibcode=2016Natur.530..177. |doi=10.1038/nature16549 |pmc=4752392 |pmid=26814963 }}

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{{Complement test comparisons|align=right}}

The diagnostic tests used to diagnose a complement deficiency include:{{Cite web |title=Complement Deficiencies Clinical Presentation: History, Physical, Causes |url=http://emedicine.medscape.com/article/135478-clinical#showall |url-status=live |archive-url=https://web.archive.org/web/20180102191532/https://emedicine.medscape.com/article/135478-clinical#showall |archive-date=2 January 2018 |access-date=21 September 2016 |website=emedicine.medscape.com}}

• 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. A C1-INH concentrate can be used for angio-oedema (C1-INH deficiency).

Pneumococcus and Haemophilus infections can be prevented via immunization. Epsilon-aminocaproic acid could be used to treat hereditary C1-INH deficiency, though the possible side effect of intravascular thrombosis should be weighed.

C2 deficiency has a prevalence of 1 in about 20,000 people in Western countries.{{Cite web |title=Complement Deficiencies. What are complement deficiencies? |url=https://patient.info/doctor/complement-deficiencies |url-status=live |archive-url=https://web.archive.org/web/20171231104021/https://patient.info/doctor/complement-deficiencies |archive-date=31 December 2017 |access-date=2017-12-31 |website=patient.info |language=en-GB}}

• Paroxysmal nocturnal hemoglobinuria

{{Reflist}}

• {{Cite journal |last=Botto |first=Marina |date=1 January 2001 |title=Links between complement deficiency and apoptosis |journal=Arthritis Research & Therapy |volume=3 |issue=4 |pages=207–210 |doi=10.1186/ar301 |pmc=128896 |pmid=11438036 |doi-access=free }}
• {{cite book |doi=10.1007/978-3-642-31785-9_8 |chapter=Complement Deficiencies |title=Clinical Cases in Primary Immunodeficiency Diseases |date=2012 |last1=Sullivan |first1=Kathleen |last2=Eibl |first2=Martha M. |last3=Erdős |first3=Melinda |last4=Maródi |first4=László |last5=Wolf |first5=Hermann M. |last6=Mahmoudi |first6=Maryam |last7=Rezaei |first7=Nima |pages=325–341 |isbn=978-3-642-31784-2 }}

{{Medical resources

| DiseasesDB = 1847

| ICD10 ={{ICD10|D|84|1|d|80}}

| ICD9 = {{ICD9|279.8}}

| ICDO =

| OMIM = 217000

| OMIM_mult = {{OMIM|120820||none}}, {{OMIM|120900||none}}, {{OMIM|610102||none}}

| MedlinePlus =

| eMedicineSubj = med

| eMedicineTopic = 419

| eMedicine_mult = {{eMedicine2|ped|447}}

| MeshID =

}}

{{Commons}}

{{Scholia|topic}}

{{Lymphoid and complement immunodeficiency}}

{{Medicine}}

{{Use dmy dates|date=April 2017}}

{{Authority control}}

Category:Noninfectious immunodeficiency-related cutaneous conditions

Category:Syndromes