Classical complement pathway: Difference between revisions

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Lack of regulation of the classical complement pathway through the deficiency in [[C1-inhibitor]] results in episodic [[angioedema]].<ref name="Overview of Complement" /> C1-inhibitor defiency can be hereditary or acquired, resulting in hereditary or acquired angioedema.<ref name="angiodema"/> C1-inhibitor plays the role of inactivating C1r and C1s to prevent further downstream classical complement activity.<ref>{{Cite journal|last=Levy|first=Michael|last2=Mealy|first2=Maureen A.|date=2014-06-01|title=Purified human C1-esterase inhibitor is safe in acute relapses of neuromyelitis optica|url=http://nn.neurology.org/content/1/1/e5|journal=Neurology - Neuroimmunology Neuroinflammation|language=en|volume=1|issue=1|pages=e5|doi=10.1212/nxi.0000000000000005|issn=2332-7812|pmid=25340061|via=}}</ref><ref name="angiodema">{{Cite journal|last=Cugno|first=Massimo|last2=Zanichelli|first2=Andrea|last3=Foieni|first3=Fabrizio|last4=Caccia|first4=Sonia|last5=Cicardi|first5=Marco|title=C1-inhibitor deficiency and angioedema: molecular mechanisms and clinical progress|url=http://linkinghub.elsevier.com/retrieve/pii/S1471491409000148|journal=Trends in Molecular Medicine|volume=15|issue=2|pages=69–78|doi=10.1016/j.molmed.2008.12.001}}</ref> C1-inhibitor controls the processes involved in maintaining vascular permeability. As a result, C1-inhibitor levels of less than 50% of the standard lead to increased vascular permeability, characteristic of angioedema.<ref name="angiodema" /> Cinryze, a human plasma derived C1-esterase inhibitor, has been approved for use in 2008 for the prevention of hereditary angioedema attacks.<ref>{{Cite journal|last=Lunn|first=Michael|date=2010-08-24|title=Cinryze&trade; as the first approved C1 inhibitor in the USA for the treatment of hereditary angioedema: approval, efficacy and safety|url=http://www.dovepress.com/cinryzetrade-as-the-first-approved-c1-inhibitor-in-the-usa-for-the-tre-peer-reviewed-article-JBM|journal=Journal of Blood Medicine|language=English|volume=1|doi=10.2147/jbm.s9576}}</ref><ref>{{cite web |url=http://www.fda.gov/biologicsbloodvaccines/bloodbloodproducts/approvedproducts/licensedproductsblas/fractionatedplasmaproducts/ucm150480.htm |title=Approval History, Letters, Reviews and Related Documents - CINRYZE |work= |accessdate=2015-01-21}}</ref>

Deficiency in the [[C1Q complex|C1q]] protein of the classical complement pathway can lead to development of [[systemic lupus erythematosus]].<ref name="Complement in disease" /><ref>{{Cite journal|last=Stegert|first=Mihaela|last2=Bock|first2=Merete|last3=Trendelenburg|first3=Marten|title=Clinical presentation of human C1q deficiency: How much of a lupus?|url=https://doi.org/10.1016/j.molimm.2015.03.007|journal=Molecular Immunology|volume=67|issue=1|pages=3–11|doi=10.1016/j.molimm.2015.03.007}}</ref> Among the many functions of C1q, C1q triggers clearance of immune complexes and apoptotic cells by activating the classical pathway and binding directly onto phagocytes.<ref name="Overview of Complement" /><ref>{{Cite journal|last=Taylor|first=Philip R.|last2=Carugati|first2=Anna|last3=Fadok|first3=Valerie A.|last4=Cook|first4=H. Terence|last5=Andrews|first5=Mark|last6=Carroll|first6=Michael C.|last7=Savill|first7=John S.|last8=Henson|first8=Peter M.|last9=Botto|first9=Marina|date=2000-08-07|title=A Hierarchical Role for Classical Pathway Complement Proteins in the Clearance of Apoptotic Cells in Vivo|journal=The Journal of Experimental Medicine|volume=192|issue=3|pages=359–366|issn=0022-1007|pmc=2193213|pmid=10934224|doi=10.1084/jem.192.3.359}}</ref> Consequently, systemic lupus erythematosus from insufficient amounts of C1q is characterized by the accumulation of autoantibodies and apoptotic cells.<ref name="C1q" /> Studies are being done to look into antibodies against C1q as a diagnostic marker for systemic lupus erythematosus.<ref>{{Cite journal|last=Chi|first=Shuhong|last2=Yu|first2=Yunxia|last3=Shi|first3=Juan|last4=Zhang|first4=Yurong|last5=Yang|first5=Jijuan|last6=Yang|first6=Lijuan|last7=Liu|first7=Xiaoming|date=2015|title=Antibodies against C1q Are a Valuable Serological Marker for Identification of Systemic Lupus Erythematosus Patients with Active Lupus Nephritis|url=http://www.hindawi.com/journals/dm/2015/450351/|journal=Disease Markers|language=en|volume=2015|pages=1–11|doi=10.1155/2015/450351|issn=0278-0240}}</ref><ref>{{Cite journal|last=Mahler|first=Michael|last2=van Schaarenburg|first2=Rosanne|last3=Trouw|first3=Leendert|date=2013|title=Anti-C1q Autoantibodies, Novel Tests, and Clinical Consequences|url=http://journal.frontiersin.org/article/10.3389/fimmu.2013.00117/abstract|journal=Frontiers in Immunology|language=English|volume=4|doi=10.3389/fimmu.2013.00117|issn=1664-3224}}</ref>

== See also ==