Editing Complement system (section)

== Role in disease ==

=== Complement deficiency ===
{{Main|Complement deficiency}}
It is thought that the complement system might play a role in many diseases with an immune component, such as [[Barraquer–Simons syndrome]], [[asthma]], [[lupus erythematosus]], [[glomerulonephritis]],  various forms of [[arthritis]], [[autoimmune heart disease]], [[multiple sclerosis]], [[inflammatory bowel disease]], [[paroxysmal nocturnal hemoglobinuria]], [[atypical hemolytic uremic syndrome]] and ischemia-reperfusion injuries,<ref name="pmid 15087815">{{Cite journal |vauthors=Arumugam TV, Shiels IA, Woodruff TM, Granger DN, Taylor SM |date=May 2004 |title=The role of the complement system in ischemia-reperfusion injury |journal=Shock |volume=21 |issue=5 |pages=401–9 |doi=10.1097/00024382-200405000-00002 |pmid=15087815 |s2cid=36655599 |doi-access=free}}</ref><ref name="pmid19443638">{{Cite journal |display-authors=6 |vauthors=Naesens M, Li L, Ying L, Sansanwal P, Sigdel TK, Hsieh SC, Kambham N, Lerut E, Salvatierra O, Butte AJ, Sarwal MM |date=August 2009 |title=Expression of complement components differs between kidney allografts from living and deceased donors |journal=Journal of the American Society of Nephrology |volume=20 |issue=8 |pages=1839–51 |doi=10.1681/ASN.2008111145 |pmc=2723986 |pmid=19443638}}</ref> and rejection of transplanted organs.<ref name="pmid 14499254">{{Cite journal |vauthors=Sacks SH, Chowdhury P, Zhou W |date=October 2003 |title=Role of the complement system in rejection |journal=Current Opinion in Immunology |volume=15 |issue=5 |pages=487–92 |doi=10.1016/S0952-7915(03)00100-6 |pmid=14499254}}</ref>

Complement regulation is suggested to play a role in pregnancy. Improper alternative complement pathway activation may mediate recurrent immune-mediated fetal loss.<ref>{{Cite journal |last1=Thurman |first1=Joshua M. |last2=Holers |first2=V. Michael |date=2006-02-01 |title=The Central Role of the Alternative Complement Pathway in Human Disease |url=https://journals.aai.org/jimmunol/article/176/3/1305/37524/The-Central-Role-of-the-Alternative-Complement |journal=The Journal of Immunology |language=en |volume=176 |issue=3 |pages=1305–1310 |doi=10.4049/jimmunol.176.3.1305 |pmid=16424154 |issn=0022-1767|url-access=subscription }}</ref><ref>{{Cite journal |last1=Mellor |first1=Andrew L. |last2=Sivakumar |first2=Jayabalan |last3=Chandler |first3=Phillip |last4=Smith |first4=Kimberly |last5=Molina |first5=Hector |last6=Mao |first6=Dailing |last7=Munn |first7=David H. |date=January 2001 |title=Prevention of T cell–driven complement activation and inflammation by tryptophan catabolism during pregnancy |url=https://www.nature.com/articles/ni0101_64 |journal=Nature Immunology |language=en |volume=2 |issue=1 |pages=64–68 |doi=10.1038/83183 |issn=1529-2908|url-access=subscription }}</ref>

The complement system is also becoming increasingly implicated in diseases of the central nervous system such as [[Alzheimer's disease]] and other neurodegenerative conditions such as spinal cord injuries.<ref>{{Cite journal |vauthors=Galvan MD, Luchetti S, Burgos AM, Nguyen HX, Hooshmand MJ, Hamers FP, Anderson AJ |date=December 2008 |title=Deficiency in complement C1q improves histological and functional locomotor outcome after spinal cord injury |journal=The Journal of Neuroscience |volume=28 |issue=51 |pages=13876–88 |doi=10.1523/JNEUROSCI.2823-08.2008 |pmc=2680920 |pmid=19091977}}</ref><ref>{{Cite journal |vauthors=Nguyen HX, Galvan MD, Anderson AJ |date=June 2008 |title=Characterization of early and terminal complement proteins associated with polymorphonuclear leukocytes in vitro and in vivo after spinal cord injury |journal=Journal of Neuroinflammation |volume=5 |pages=26 |doi=10.1186/1742-2094-5-26 |pmc=2443364 |pmid=18578885 |doi-access=free}}</ref><ref>{{Cite journal |vauthors=Beck KD, Nguyen HX, Galvan MD, Salazar DL, Woodruff TM, Anderson AJ |date=February 2010 |title=Quantitative analysis of cellular inflammation after traumatic spinal cord injury: evidence for a multiphasic inflammatory response in the acute to chronic environment |journal=Brain |volume=133 |issue=Pt 2 |pages=433–47 |doi=10.1093/brain/awp322 |pmc=2858013 |pmid=20085927}}</ref>

Deficiencies of the terminal pathway predispose to both [[autoimmune disease]] and [[infection]]s (particularly [[Neisseria meningitidis]], due to the role that the [[membrane attack complex]] ("MAC") plays in attacking [[Gram-negative]] bacteria).<ref>{{Cite book |title=Bacteria and Complement |vauthors=Brown EJ |date=1985 |publisher=Springer, Berlin, Heidelberg |isbn=9783642456060 |series=Current Topics in Microbiology and Immunology |volume=121 |pages=159–187 |language=en |chapter=Interaction of Gram-Positive Microorganisms with Complement |doi=10.1007/978-3-642-45604-6_8 |pmid=3936681}}</ref>

Infections with ''N. meningitidis'' and ''[[N. gonorrhoeae]]'' are the only conditions known to be associated with deficiencies in the MAC components of complement.<ref name="Ram2010">{{Cite journal |vauthors=Ram S, Lewis LA, Rice PA |date=October 2010 |title=Infections of people with complement deficiencies and patients who have undergone splenectomy |journal=Clinical Microbiology Reviews |volume=23 |issue=4 |pages=740–80 |doi=10.1128/CMR.00048-09 |pmc=2952982 |pmid=20930072}}</ref>  40–50% of those with MAC deficiencies experience recurrent infections with ''N. meningitidis''.<ref name="Lewis2014">{{Cite journal |vauthors=Lewis LA, Ram S |date=January 2014 |title=Meningococcal disease and the complement system |journal=Virulence |volume=5 |issue=1 |pages=98–126 |doi=10.4161/viru.26515 |pmc=3916388 |pmid=24104403}}</ref>

=== Deficiencies in complement regulators ===

Mutations in the genes of complement regulators, especially [[factor H]], have been associated with atypical [[hemolytic uremic syndrome]],<ref name=":0" /><ref name="pmid16189652">{{Cite journal |vauthors=Dragon-Durey MA, Frémeaux-Bacchi V |date=November 2005 |title=Atypical haemolytic uraemic syndrome and mutations in complement regulator genes |journal=Springer Seminars in Immunopathology |volume=27 |issue=3 |pages=359–74 |doi=10.1007/s00281-005-0003-2 |pmid=16189652 |s2cid=6330326}}</ref><ref name="pmid16575689">{{Cite journal |vauthors=Zipfel PF, Misselwitz J, Licht C, Skerka C |date=March 2006 |title=The role of defective complement control in hemolytic uremic syndrome |journal=Seminars in Thrombosis and Hemostasis |volume=32 |issue=2 |pages=146–54 |doi=10.1055/s-2006-939770 |pmid=16575689 |s2cid=260316508}}</ref> and C3 glomerulopathy.<ref name=":0" /> Both of these disorders are currently thought to be due to complement overactivation either on the surface of host cells or in plasma, with the molecular location of genetic variation in complement proteins providing clues into the underlying disease processes.<ref name=":0" /> Moreover, several [[single nucleotide polymorphism]]s and mutations in the complement factor H gene (the most common of which results in the protein change p.Y402H) have been associated with the common eye disease [[age-related macular degeneration]].<ref name=":0" /> Polymorphisms of [[complement component 3]], [[complement factor B]], and [[complement factor I]], as well as deletion of complement factor H-related 3 and complement factor H-related 1, also affect a person's risk of developing [[age-related macular degeneration]].<ref name=":0" /><ref name="BradleyDT2011">{{Cite journal |vauthors=Bradley DT, Zipfel PF, Hughes AE |date=June 2011 |title=Complement in age-related macular degeneration: a focus on function |journal=Eye |volume=25 |issue=6 |pages=683–93 |doi=10.1038/eye.2011.37 |pmc=3178140 |pmid=21394116}}</ref>

Mutations in the C1 inhibitor gene can cause [[hereditary angioedema]], a genetic condition resulting from reduced regulation of [[bradykinin]] by C1-INH.{{citation needed|date=May 2015}}

[[Paroxysmal nocturnal hemoglobinuria]] is caused by complement breakdown of [[Red blood cell|RBC]]s due to an inability to make GPI. Thus the RBCs are not protected by GPI anchored proteins such as DAF.<ref>{{Cite journal |display-authors=6 |vauthors=Parker C, Omine M, Richards S, Nishimura J, Bessler M, Ware R, Hillmen P, Luzzatto L, Young N, Kinoshita T, Rosse W, Socié G |date=December 2005 |title=Diagnosis and management of paroxysmal nocturnal hemoglobinuria |journal=Blood |volume=106 |issue=12 |pages=3699–709 |doi=10.1182/blood-2005-04-1717 |pmc=1895106 |pmid=16051736}}</ref>

=== Diagnostic tools ===
Diagnostic tools to measure complement activity include the [[total complement activity]] test.<ref>{{Cite web |title=Complement Deficiencies Workup: Laboratory Studies, Imaging Studies, Other Tests |url=https://emedicine.medscape.com/article/135478-workup |access-date=2018-04-26 |website=emedicine.medscape.com |language=en}}</ref>

The presence or absence of complement fixation upon a challenge can indicate whether particular antigens or antibodies are present in the blood. This is the principle of the [[complement fixation test]].{{cn|date=July 2024}}