Classical complement pathway: Difference between revisions

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Revision as of 20:24, 3 February 2019

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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?|journal=Molecular Immunology|volume=67|issue=1|pages=3–11|doi=10.1016/j.molimm.2015.03.007|pmid=25846716|year=2015}}</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=450351|doi=10.1155/2015/450351|pmid=26549923|pmc=4621353|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|journal=Frontiers in Immunology|language=English|volume=4|pages=117|doi=10.3389/fimmu.2013.00117|pmid=23717311|pmc=3653116|issn=1664-3224}}</ref>

ApoE qualifies as a checkpoint inhibitor of the classical complement pathway via formation of the C1q–ApoE complex. C1q–ApoE complexes emerged as markers for ongoing complement activity of diseased choroid plexus, Aβ plaques, and atherosclerosis in vivo. C1q–ApoE complexes in human choroid plexus, Aβ plaques, and arteries correlated with cognitive decline and atherosclerosis, respectively. Deficiency in ApoE in mice leads to strongly upregulated of the classical complement cascade activation in atherosclerosis and choroid plexus inflammation. Treatment with small interfering RNA (siRNA) against C5 in ApoE knockout mice attenuated murine choroid plexus inflammation and atherosclerosis <ref>{{cite journal | vauthors = Yin C, Ackermann S, Ma Z, Mohanta SK, Zhang C, Li Y, Nietzsche S, Westermann M, Peng L, Hu D, Bontha SV, Srikakulapu P, Beer M, Megens RTA, Steffens S, Hildner M, Halder LD, Eckstein HH, Pelisek J, Herms J, Roeber S, Arzberger T, Borodovsky A, Habenicht L, Binder CJ, Weber C, Zipfel PF, Skerka C, Habenicht AJR. | title = ApoE attenuates unresolvable inflammation by complex formation with activated C1q | language = en|journal= Nature Medicine|date = January 2019 | pmid = 30692699 | doi = 10.1038/s41591-018-0336-8}}</ref>

== See also ==

* [[Alternative complement pathway]] – another complement system pathway

* [[Lectin pathway]] – another complement system pathway