imported>Chris Capoccia at 18:12, 28 January 2025

2025-01-28T18:12:43Z

New page

{{Infobox medical condition (new)
| name = Complement deficiency
| image = Complement pathway.svg
| caption = Complement pathway (normal)
| pronounce =
| field =
| synonyms =
| symptoms = Recurring infection, rheumatic disease<ref name=osk/>
| complications =
| onset =
| duration =
| types =
| causes = Can be inherited or acquired<ref name=pat/>
| risks =
| diagnosis = CH50 measurement, Plasma level<ref name=scape/>
| differential =
| prevention =
| treatment = Immunosuppressive therapy<ref name=pat/>
| medication =
| prognosis =
| frequency =
| deaths =
}}
'''Complement deficiency''' is an [[immunodeficiency]] of absent or suboptimal functioning of one of the [[complement system]] proteins.<ref name="GorbachBartlett2004">{{Cite book |last=Winkelstein |first=Jerry A. |title=Infectious Diseases |date=2004 |publisher=Lippincott Williams & Wilkins |isbn=978-0-7817-3371-7 |editor-last=Gorbach |editor-first=Sherwood L. |pages=8–13 |chapter=The Complement System |editor-last2=Bartlett |editor-first2=John G. |editor-last3=Blacklow |editor-first3=Neil R.}}</ref> Because of redundancies in the [[immune system]], many complement disorders are never diagnosed. Some studies estimate that less than 10% are identified.<ref>{{Cite journal |last=Sjöholm |first=A.G. |last2=Jönsson |first2=G. |last3=Braconier |first3=J.H. |last4=Sturfelt |first4=G. |last5=Truedsson |first5=L. |year=2006 |title=Complement deficiency and disease: An update |journal=Molecular Immunology |volume=43 |issue=1–2 |pages=78–85 |doi=10.1016/j.molimm.2005.06.025 |pmid=16026838 }}</ref> ''Hypocomplementemia'' may be used more generally to refer to decreased complement levels,<ref>{{cite book |doi=10.1007/3-540-29662-X_1306 |chapter=Hypocomplementemia |title=Rheumatology and Immunology Therapy |date=2004 |page=425 |isbn=3-540-20625-6 |editor1-first=Larry W. |editor1-last=Moreland |chapter-url={{GBurl|GiR493YLsgsC|p=425}} }}</ref> while ''secondary complement disorder'' means decreased complement levels that are not directly due to a genetic cause but secondary to another medical condition.<ref name="emed">{{EMedicine|article|136368|Complement-Related Disorders}}</ref>

==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]].<ref>{{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 }}</ref>
* Disorders of the proteins that act to '''''activate''''' the complement system (such as [[complement component 3|C3]]) can lead to an ''underactive'' response, causing greater susceptibility to infections.<ref>{{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 }}</ref>

==Signs and symptoms==
The following symptoms (signs) are consistent with complement deficiency in general:<ref name="osk">{{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}}</ref><ref name=scape/><ref>{{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 }}</ref>
{{columns-list|colwidth=30em|
* Recurring [[infection]]
* [[Auto-immune disorders]]
* [[Glomerulonephritis]]
* [[Joint]] problems (manifestation)
* [[Lung]] function (MBL variant alleles)
* [[Angioedema]]
* [[Dermatomyositis]]
* [[Vasculitis]]
* [[Anaphylactoid purpura]]
}}

===Complications===
[[File:Neisseria-meningitidis-Differentially-Controls-Host-Cell-Motility-through-PilC1-and-PilC2-pone.0006834.s003.ogv|thumb|230 px|Neisseria, a possible complication]]

[[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]]''.<ref>{{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}}</ref>

==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]] [[recessive]] conditions, while [[properdin deficiency]] occurs through [[X-linked]] inheritance. [[MBL deficiency]] can be inherited by either manner.<ref name=pat/>

===Inherited===
* [[Properdin deficiency]] is an [[X-linked]]<ref>{{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}}</ref> disorder that also causes susceptibility to ''[[Neisseria]]'' infections.<ref name=pat/>
* C1-inhibitor deficiency or [[hereditary angioedema]] will have low C4 with normal C1 levels.<ref>{{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 }}</ref>

===Acquired===
Acquired hypocomplementemia may occur in the setting of [[osteomyelitis|bone infections (osteomyelitis)]], [[endocarditis|infection of the lining of the heart (endocarditis)]], and [[cryoglobulinemia]]. [[Systemic lupus erythematosus]] is associated with low [[Complement component 3|C3]] and [[Complement component 4|C4]].<ref>{{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}}</ref> [[Membranoproliferative glomerulonephritis]] usually has low C3.<ref>{{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}}</ref>

==Mechanism==
[[File:Genetic Risk of Schizophrenia Summary Figure.png|thumb|right|500 px|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 [[complement component 2|C2]] deficiency, about 5 different [[mutation]]s in the ''C2'' [[gene]] are responsible. In turn, immune function decreases and infection opportunities increase. One of the most common mutations deletes 28 DNA [[nucleotide]]s from the ''C2'' gene. Therefore, no C2 [[protein]] which can help make [[C3-convertase]] is produced. Ultimately, this delays/decreases immune response.<ref>{{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}}</ref>
* '''C3''': In terms of deficiency of [[complement component 3|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.<ref>{{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}}</ref>
* '''C4''': [[complement component 4|C4]] deficiency is highly associated with [[systemic lupus erythematosus]].<ref name=scape/> [[Amyloid beta|Aβ42]], a protein involved in [[Alzheimer's disease]], can cause activation of C4 (even in plasma deficient of [[C1q]]).<ref>{{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 }}</ref> At least one study indicates that the genetic variation of C4 plays a role in [[schizophrenia]].<ref>{{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 }}</ref>
{{clear}}

==Diagnosis==
{{Complement test comparisons|align=right}}
The diagnostic tests used to diagnose a complement deficiency include:<ref name="scape">{{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}}</ref>
* [[CH50]] measurement
* [[Immunochemistry|Immunochemical]] methods/test
* [[Complement component 3|C3]] deficiency screening
* [[Mannose]]-binding lectin (lab study)
* [[Blood plasma|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).<ref name=pat/><ref name=scape/>

[[Pneumococcus]] and ''[[Haemophilus]]'' infections can be prevented via immunization.<ref name=pat/> [[Epsilon-aminocaproic acid]] could be used to treat hereditary C1-INH deficiency, though the possible side effect of [[intravascular]] [[thrombosis]] should be weighed.<ref name=emed/>

==Epidemiology==
C2 deficiency has a prevalence of 1 in about 20,000 people in [[Western countries]].<ref name="pat">{{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}}</ref>

==See also==
* [[Paroxysmal nocturnal hemoglobinuria]]

== References ==
{{Reflist}}

==Further reading==
* {{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 }}

== External links ==
{{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:Complement deficiency| ]]
[[Category:Noninfectious immunodeficiency-related cutaneous conditions]]
[[Category:Syndromes]]

Complement deficiency - Revision history

imported>Chris Capoccia at 18:12, 28 January 2025