factor H

The molecule is made up of 20 complement control protein (CCP) modules (also referred to as Short Consensus Repeats or sushi domains) connected to one another by short linkers (of between three and eight amino acid residues) and arranged in an extended head to tail fashion. Each of the CCP modules consists of around 60 amino acids with four cysteine residues disulfide bonded in a 1–3 2–4 arrangement, and a hydrophobic core built around an almost invariant tryptophan residue. The CCP modules are numbered from 1–20 (from the N-terminus of the protein); CCPs 1–4 and CCPs 19–20 engage with C3b while CCPs 7 and CCPs 19–20 bind to GAGs and sialic acid.{{cite journal | vauthors = Schmidt CQ, Herbert AP, Kavanagh D, Gandy C, Fenton CJ, Blaum BS, Lyon M, Uhrín D, Barlow PN | title = A new map of glycosaminoglycan and C3b binding sites on factor H | journal = Journal of Immunology | volume = 181 | issue = 4 | pages = 2610–2619 | date = August 2008 | pmid = 18684951 | doi = 10.4049/jimmunol.181.4.2610 | doi-access = free }} To date atomic structures have been determined for CCPs 1–3,{{cite journal | vauthors = Hocking HG, Herbert AP, Kavanagh D, Soares DC, Ferreira VP, Pangburn MK, Uhrín D, Barlow PN | title = Structure of the N-terminal region of complement factor H and conformational implications of disease-linked sequence variations | journal = The Journal of Biological Chemistry | volume = 283 | issue = 14 | pages = 9475–9487 | date = April 2008 | pmid = 18252712 | pmc = 2276370 | doi = 10.1074/jbc.M709587200 | doi-access = free }} CCP 5,{{cite journal | vauthors = Barlow PN, Norman DG, Steinkasserer A, Horne TJ, Pearce J, Driscoll PC, Sim RB, Campbell ID | title = Solution structure of the fifth repeat of factor H: a second example of the complement control protein module | journal = Biochemistry | volume = 31 | issue = 14 | pages = 3626–3634 | date = April 1992 | pmid = 1533152 | doi = 10.1021/bi00129a011 }} CCP 7,{{cite journal | vauthors = Herbert AP, Deakin JA, Schmidt CQ, Blaum BS, Egan C, Ferreira VP, Pangburn MK, Lyon M, Uhrín D, Barlow PN | title = Structure shows that a glycosaminoglycan and protein recognition site in factor H is perturbed by age-related macular degeneration-linked single nucleotide polymorphism | journal = The Journal of Biological Chemistry | volume = 282 | issue = 26 | pages = 18960–18968 | date = June 2007 | pmid = 17360715 | doi = 10.1074/jbc.M609636200 | doi-access = free }} CCPs 10–11 and CCPs 11–12,{{cite journal | vauthors = Makou E, Mertens HD, Maciejewski M, Soares DC, Matis I, Schmidt CQ, Herbert AP, Svergun DI, Barlow PN | title = Solution structure of CCP modules 10-12 illuminates functional architecture of the complement regulator, factor H | journal = Journal of Molecular Biology | volume = 424 | issue = 5 | pages = 295–312 | date = December 2012 | pmid = 23017427 | pmc = 4068365 | doi = 10.1016/j.jmb.2012.09.013 }} CCPs 12–13,{{cite journal | vauthors = Schmidt CQ, Herbert AP, Mertens HD, Guariento M, Soares DC, Uhrin D, Rowe AJ, Svergun DI, Barlow PN | title = The central portion of factor H (modules 10-15) is compact and contains a structurally deviant CCP module | journal = Journal of Molecular Biology | volume = 395 | issue = 1 | pages = 105–122 | date = January 2010 | pmid = 19835885 | pmc = 2806952 | doi = 10.1016/j.jmb.2009.10.010 }} CCP 15, CCP 16,{{cite journal | vauthors = Norman DG, Barlow PN, Baron M, Day AJ, Sim RB, Campbell ID | title = Three-dimensional structure of a complement control protein module in solution | journal = Journal of Molecular Biology | volume = 219 | issue = 4 | pages = 717–725 | date = June 1991 | pmid = 1829116 | doi = 10.1016/0022-2836(91)90666-T }} CCPs 15–16,{{cite journal | vauthors = Barlow PN, Steinkasserer A, Norman DG, Kieffer B, Wiles AP, Sim RB, Campbell ID | title = Solution structure of a pair of complement modules by nuclear magnetic resonance | journal = Journal of Molecular Biology | volume = 232 | issue = 1 | pages = 268–284 | date = July 1993 | pmid = 8331663 | doi = 10.1006/jmbi.1993.1381 }} CCPs 18–20,{{cite journal | vauthors = Morgan HP, Mertens HD, Guariento M, Schmidt CQ, Soares DC, Svergun DI, Herbert AP, Barlow PN, Hannan JP | title = Structural analysis of the C-terminal region (modules 18-20) of complement regulator factor H (FH) | journal = PLOS ONE | volume = 7 | issue = 2 | pages = e32187 | year = 2012 | pmid = 22389686 | pmc = 3289644 | doi = 10.1371/journal.pone.0032187 | doi-access = free | bibcode = 2012PLoSO...732187M }} and CCPs 19–20.{{cite journal | vauthors = Herbert AP, Uhrín D, Lyon M, Pangburn MK, Barlow PN | title = Disease-associated sequence variations congregate in a polyanion recognition patch on human factor H revealed in three-dimensional structure | journal = The Journal of Biological Chemistry | volume = 281 | issue = 24 | pages = 16512–16520 | date = June 2006 | pmid = 16533809 | doi = 10.1074/jbc.M513611200 | doi-access = free }}{{cite journal | vauthors = Jokiranta TS, Jaakola VP, Lehtinen MJ, Pärepalo M, Meri S, Goldman A | title = Structure of complement factor H carboxyl-terminus reveals molecular basis of atypical haemolytic uremic syndrome | journal = The EMBO Journal | volume = 25 | issue = 8 | pages = 1784–1794 | date = April 2006 | pmid = 16601698 | pmc = 1440827 | doi = 10.1038/sj.emboj.7601052 }} The atomic structure for CCPs 6–8 bound to the GAG mimic sucrose octasulfate,{{cite journal | vauthors = Prosser BE, Johnson S, Roversi P, Herbert AP, Blaum BS, Tyrrell J, Jowitt TA, Clark SJ, Tarelli E, Uhrín D, Barlow PN, Sim RB, Day AJ, Lea SM | title = Structural basis for complement factor H linked age-related macular degeneration | journal = The Journal of Experimental Medicine | volume = 204 | issue = 10 | pages = 2277–2283 | date = October 2007 | pmid = 17893204 | pmc = 2118454 | doi = 10.1084/jem.20071069 }} CCPs 1–4 in complex with C3b{{cite journal | vauthors = Wu J, Wu YQ, Ricklin D, Janssen BJ, Lambris JD, Gros P | title = Structure of complement fragment C3b-factor H and implications for host protection by complement regulators | journal = Nature Immunology | volume = 10 | issue = 7 | pages = 728–733 | date = July 2009 | pmid = 19503104 | pmc = 2713992 | doi = 10.1038/ni.1755 }} and CCPs 19–20 in complex with C3d (that corresponds to the thioester domain of C3b){{cite journal | vauthors = Morgan HP, Schmidt CQ, Guariento M, Blaum BS, Gillespie D, Herbert AP, Kavanagh D, Mertens HD, Svergun DI, Johansson CM, Uhrín D, Barlow PN, Hannan JP | title = Structural basis for engagement by complement factor H of C3b on a self surface | journal = Nature Structural & Molecular Biology | volume = 18 | issue = 4 | pages = 463–470 | date = April 2011 | pmid = 21317894 | pmc = 3512577 | doi = 10.1038/nsmb.2018 }}{{cite journal | vauthors = Kajander T, Lehtinen MJ, Hyvärinen S, Bhattacharjee A, Leung E, Isenman DE, Meri S, Goldman A, Jokiranta TS | title = Dual interaction of factor H with C3d and glycosaminoglycans in host-nonhost discrimination by complement | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 108 | issue = 7 | pages = 2897–2902 | date = February 2011 | pmid = 21285368 | pmc = 3041134 | doi = 10.1073/pnas.1017087108 | doi-access = free | bibcode = 2011PNAS..108.2897K }} have also been determined. Although an atomic resolution structure for intact factor H has not yet been determined, low resolution techniques indicate that it may be bent back in solution.{{cite journal | vauthors = Aslam M, Perkins SJ | title = Folded-back solution structure of monomeric factor H of human complement by synchrotron X-ray and neutron scattering, analytical ultracentrifugation and constrained molecular modelling | journal = Journal of Molecular Biology | volume = 309 | issue = 5 | pages = 1117–1138 | date = June 2001 | pmid = 11399083 | doi = 10.1006/jmbi.2001.4720 }} Information available to date indicates that CCP modules 1–4 is responsible for the cofactor and decay acceleration activities of factor H, whereas self/non-self discrimination occurs predominantly through GAG binding to CCP modules 7 and/or GAG or sialic acid binding to 19–20.{{cite journal | vauthors = Kirkitadze MD, Barlow PN | title = Structure and flexibility of the multiple domain proteins that regulate complement activation | journal = Immunological Reviews | volume = 180 | pages = 146–161 | date = April 2001 | pmid = 11414356 | doi = 10.1034/j.1600-065X.2001.1800113.x | s2cid = 25095717 }}

The principal role of Factor H is to regulate the alternative pathway of the complement system, a key component of innate immunity. It ensures that complement activation is directed against pathogens or abnormal surfaces, while preventing damage to host tissues. This is accomplished through two main mechanisms: serving as a cofactor for Factor I-mediated cleavage of C3b, and accelerating the decay of the alternative pathway C3-convertase, C3bBb.

Factor H selectively exerts its regulatory activity on self cells and surfaces, but not on the surfaces of bacteria or viruses. However, some pathogens, such as Neisseria meningitidis (the meningococcus), have evolved mechanisms to bind human FH, thereby evading complement-mediated destruction.{{cite journal | vauthors = Lewis LA, Carter M, Ram S | title = The relative roles of factor H binding protein, neisserial surface protein A, and lipooligosaccharide sialylation in regulation of the alternative pathway of complement on meningococci | journal = Journal of Immunology | volume = 188 | issue = 10 | pages = 5063–5072 | date = May 2012 | pmid = 22504643 | pmc = 3345070 | doi = 10.4049/jimmunol.1103748 }} This interaction enables the bacteria to survive and proliferate in the bloodstream, contributing to invasive disease.{{cite journal | vauthors = Vu DM, Shaughnessy J, Lewis LA, Ram S, Rice PA, Granoff DM | title = Enhanced bacteremia in human factor H transgenic rats infected by Neisseria meningitidis | journal = Infection and Immunity | volume = 80 | issue = 2 | pages = 643–650 | date = February 2012 | pmid = 22104107 | pmc = 3264313 | doi = 10.1128/IAI.05604-11 | veditors = Bliska JB }}

The ability of Factor H to protect self surfaces is believed to depend on its capacity to adopt different conformational states, each associated with varying levels of cofactor and decay-accelerating activity.{{cite journal | vauthors = Herbert AP, Makou E, Chen ZA, Kerr H, Richards A, Rappsilber J, Barlow PN | title = Complement Evasion Mediated by Enhancement of Captured Factor H: Implications for Protection of Self-Surfaces from Complement | journal = Journal of Immunology | volume = 195 | issue = 10 | pages = 4986–4998 | date = November 2015 | pmid = 26459349 | pmc = 4635569 | doi = 10.4049/jimmunol.1501388 }} In solution, FH predominantly exists in a low-activity conformation sufficient to regulate complement in the fluid phase. Upon binding to glycosaminoglycans (GAGs) or sialic acids—molecules typically found on host cells—FH undergoes conformational changes that enhance its regulatory function. This mechanism ensures that complement activation is inhibited on self surfaces while proceeding unimpeded on foreign cells.{{cite journal | vauthors = Pangburn MK | title = Host recognition and target differentiation by factor H, a regulator of the alternative pathway of complement | journal = Immunopharmacology | volume = 49 | issue = 1–2 | pages = 149–157 | date = August 2000 | pmid = 10904114 | doi = 10.1016/S0162-3109(00)80300-8 }}{{cite journal | vauthors = Rodríguez de Córdoba S, Esparza-Gordillo J, Goicoechea de Jorge E, Lopez-Trascasa M, Sánchez-Corral P | title = The human complement factor H: functional roles, genetic variations and disease associations | journal = Molecular Immunology | volume = 41 | issue = 4 | pages = 355–367 | date = June 2004 | pmid = 15163532 | doi = 10.1016/j.molimm.2004.02.005 }}

Due to the central role that factor H plays in the regulation of complement, there are a number of clinical implications arising from aberrant factor H activity. Overactive factor H may result in reduced complement activity on pathogenic cells – increasing susceptibility to microbial infections. Underactive factor H may result in increased complement activity on healthy host cells – resulting in autoimmune diseases. It is not surprising, therefore, that rare mutations or common single nucleotide polymorphisms (SNPs) in the complement factor H gene (CFH) often result in pathologies. Moreover, the complement inhibitory activities of factor H, and other complement regulators, are often used by pathogens to increase virulence.

In 2005, several independent research groups identified an SNP in CFH, which results in the protein change p.Y402H, as a risk factor for Age Related Macular Degeneration (AMD) present in around a third of Europeans.{{cite journal | vauthors = Tzoumas N, Hallam D, Harris CL, Lako M, Kavanagh D, Steel DH | title = Revisiting the role of factor H in age-related macular degeneration: Insights from complement-mediated renal disease and rare genetic variants | journal = Survey of Ophthalmology | volume = 66 | issue = 2 | pages = 378–401 | date = November 2020 | pmid = 33157112 | doi = 10.1016/j.survophthal.2020.10.008 | s2cid = 226274874 }} Although its allele frequency varies considerably between different populations, Y402H has been consistently associated with AMD onset and progression. Homozygous individuals have an approximately seven-fold greater odds of association with AMD while heterozygotes have a two-to-three-fold greater odds of association with the disease. This SNP, located in CCP module 7 of factor H, has been shown to affect the ability of factor H protein to localise to sites of inflammation in retinal tissues (e.g. by polyanions and pentraxins) and to regulate the activation of complement and immune cells. The SNP has also been shown to affect the function of factor H-like protein 1, an alternatively spliced version of factor H consisting of CCPs 1 to 7 only, which is thought to have a greater role in intraocular complement regulation. The British complementologist, Simon J. Clark demonstrated that FHL-1 was the predominant form of FH protecting Bruch's membrane,{{cite journal | vauthors = Clark SJ, Schmidt CQ, White AM, Hakobyan S, Morgan BP, Bishop PN | title = Identification of factor H-like protein 1 as the predominant complement regulator in Bruch's membrane: implications for age-related macular degeneration | journal = Journal of Immunology | volume = 193 | issue = 10 | pages = 4962–4970 | date = November 2014 | pmid = 25305316 | pmc = 4225158 | doi = 10.4049/jimmunol.1401613 }} an integral part of the outer Blood-retinal barrier and a major site of early AMD. Further studies suggested that haploinsufficiency of FHL-1 lead to the manifestation of an AMD-like disease at a significantly earlier age.{{cite journal | vauthors = Taylor RL, Poulter JA, Downes SM, McKibbin M, Khan KN, Inglehearn CF, Webster AR, Hardcastle AJ, Michaelides M, Bishop PN, Clark SJ, Black GC | title = Loss-of-Function Mutations in the CFH Gene Affecting Alternatively Encoded Factor H-like 1 Protein Cause Dominant Early-Onset Macular Drusen | journal = Ophthalmology | volume = 126 | issue = 10 | pages = 1410–1421 | date = October 2019 | pmid = 30905644 | pmc = 6856713 | doi = 10.1016/j.ophtha.2019.03.013 }} However, the genetic variants in CFH with the greatest effect on an individual's risk of AMD have been shown to affect CCPs 1 to 4, which are involved in dampening the effects of the alternative pathway of complement. A rare functional coding change, p.R1210C, in CFH results in a functional deficiency in factor H and leads to a substantially higher risk of macular degeneration as well as complement-mediated renal conditions.{{cite journal | vauthors = Raychaudhuri S, Iartchouk O, Chin K, Tan PL, Tai AK, Ripke S, Gowrisankar S, Vemuri S, Montgomery K, Yu Y, Reynolds R, Zack DJ, Campochiaro B, Campochiaro P, Katsanis N, Daly MJ, Seddon JM | title = A rare penetrant mutation in CFH confers high risk of age-related macular degeneration | journal = Nature Genetics | volume = 43 | issue = 12 | pages = 1232–1236 | date = October 2011 | pmid = 22019782 | pmc = 3225644 | doi = 10.1038/ng.976 }}

Variation in other genes of the regulators of complement activation locus, such as complement factor H-related genes, as well as in other complement proteins (e.g. factor I, C2/factor B, and C3) have also been associated with greater AMD risk. The current theory is that complement dysregulation is a key driver of chronic inflammation in AMD.

Gemini Therapeutics Inc. was a Massachusetts based precision medicine company focused on the development of new therapies through a deeper understanding of disease. Based on the biological activity of human factor H, Gemini was developing a recombinant human factor H protein, GEM103, for the treatment of dry AMD. GEM-103 was evaluated in phase I (NCT04246866) and II (NCT04643886) clinical trials in AMD patients, but failed to achieve its clinical end points and the developmental program was terminated{{cite web|url=https://clinicaltrials.gov/study/NCT04643886?term=NCT04643886&rank=1|title=ClinicalTrials.gov NCT04643886|date=22 September 2022 }} Gemini Therapeutics merged with Disc Medicine in 2022{{cite web|url=https://www.businesswire.com/news/home/20220810005215/en/Gemini-Therapeutics-and-Disc-Medicine-Announce-Merger-Agreement|title=businesswire press release 10th August 2022}}

Other companies currently focusing on developing FH, FHL-1, or variations thereof, as therapeutics for treating AMD, include Character Biosciences Inc,{{cite web|url=https://iovs.arvojournals.org/article.aspx?articleid=2794591|title=ARVO abstract June 2024}} and 4D Molecular Therapeutics{{cite web|url=https://iovs.arvojournals.org/article.aspx?articleid=2794900|title=ARVO abstract June 2024}}

Hemolytic uremic syndrome (HUS) is a disease associated with microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. It can be either acquired (e.g. following infection with shigatoxigenic Escherichia coli), or inherited (also known as atypical hemolytic uremic syndrome, aHUS). aHUS has been strongly linked to mutations in genes of the complement system, especially factor H. In contrast to AMD and C3 glomerulopathy (another complement-mediated renal disorder) which are mainly associated with variation in the N-terminus (CCPs 1 to 4), predisposing mutations in factor H mainly affect the C-terminus of the protein (CCP modules 19 and 20), which has been shown to be responsible for adherence to renal tissues and the regulation of complement components and their downstream effectors.{{cite journal | vauthors = Atkinson JP, Goodship TH | title = Complement factor H and the hemolytic uremic syndrome | journal = The Journal of Experimental Medicine | volume = 204 | issue = 6 | pages = 1245–1248 | date = June 2007 | pmid = 17548524 | pmc = 2118604 | doi = 10.1084/jem.20070664 }}{{cite journal | vauthors = de Jorge EG, Macor P, Paixão-Cavalcante D, Rose KL, Tedesco F, Cook HT, Botto M, Pickering MC | title = The development of atypical hemolytic uremic syndrome depends on complement C5 | journal = Journal of the American Society of Nephrology | volume = 22 | issue = 1 | pages = 137–145 | date = January 2011 | pmid = 21148255 | pmc = 3014042 | doi = 10.1681/ASN.2010050451 }}

Alterations in the immune response are involved in pathogenesis of many neuropsychiatric disorders including schizophrenia. Recent studies indicated alterations in the complement system, including those which may result in the overactivation of the alternative complement pathway, may predispose to schizophrenia. For example, the CFH SNP rs424535 (2783-526T>A) was positively associated with schizophrenia.{{cite journal | vauthors = Boyajyan A, Ghazaryan H, Stepanyan A, Zakharyan R | title = Genetic polymorphisms of complement factor H in schizophrenia and ischemic stroke | journal = Mol. Immunol. | volume = 56 | issue = 3 | pages = 294 |date = December 2013 | doi = 10.1016/j.molimm.2013.05.154 }}

It was found that rs800292(184G >A) SNP was positively associated with stroke and rs800912 minor allele of the CFH gene might be considered as a risk factor for ischemic stroke.

Given the central role of factor H in protecting cells from complement, it is not surprising that several important human pathogens have evolved mechanisms for recruiting factor H. This recruitment of factor H by pathogens provides significant resistance to complement attack, and therefore increased virulence. Pathogens that have been shown to recruit factor H include: Aspergillus spp.; Borrelia burgdorferi; B. duttonii; B. recurrentis; Candida albicans;{{cite journal | vauthors = Luo S, Poltermann S, Kunert A, Rupp S, Zipfel PF | title = Immune evasion of the human pathogenic yeast Candida albicans: Pra1 is a Factor H, FHL-1 and plasminogen binding surface protein | journal = Molecular Immunology | volume = 47 | issue = 2–3 | pages = 541–550 | date = December 2009 | pmid = 19850343 | doi = 10.1016/j.molimm.2009.07.017 }} Francisella tularensis; Haemophilus influenzae; Neisseria gonorrhoeae;{{cite journal | vauthors = Ram S, Sharma AK, Simpson SD, Gulati S, McQuillen DP, Pangburn MK, Rice PA | title = A novel sialic acid binding site on factor H mediates serum resistance of sialylated Neisseria gonorrhoeae | journal = The Journal of Experimental Medicine | volume = 187 | issue = 5 | pages = 743–752 | date = March 1998 | pmid = 9480984 | pmc = 2212180 | doi = 10.1084/jem.187.5.743 }} N. meningitidis; Streptococcus pneumoniae; and Streptococcus pyogenes.{{cite journal|vauthors=Syed S, Viazmina L, Mager R, Meri S, Haapasalo K|title=Streptococci and the complement system: interplay during infection, inflammation and autoimmunity|journal=FEBS Letters|volume=594|issue=16|pages=2570–2585|year=2020|publisher=Federation of European Biochemical Societies|doi=10.1002/1873-3468.13872|doi-access=free|pmid=32594520|hdl=10138/326342|hdl-access=free}}

The Gram-negative bacterium B. burgdorferi has five factor H–binding proteins: CRASP-1, CRASP-2, CRASP-3, CRASP-4 and CRASP-5.{{cite journal | vauthors = Zipfel PF, Hallström T, Riesbeck K | title = Human complement control and complement evasion by pathogenic microbes—tipping the balance | journal = Molecular Immunology | volume = 56 | issue = 3 | pages = 152–160 | date = December 2013 | pmid = 23810413 | doi = 10.1016/j.molimm.2013.05.222 | s2cid = 207007297 | url = https://lup.lub.lu.se/record/4027108 }} Each CRASP protein also binds plasminogen. It is possible that the allele frequency of CFH variants across the globe reflects selective pressure from infectious diseases.

Factor H has been shown to interact with complement component 3, amongst other complement proteins and factors, leading to regulation of the alternative pathway of complement in particular.{{cite journal | vauthors = Soames CJ, Sim RB | title = Interactions between human complement components factor H, factor I and C3b | journal = The Biochemical Journal | volume = 326 | issue = Pt 2 | pages = 553–561 | date = September 1997 | pmid = 9291131 | pmc = 1218704 | doi = 10.1042/bj3260553 }}{{cite journal | vauthors = Jokiranta TS, Westin J, Nilsson UR, Nilsson B, Hellwage J, Löfås S, Gordon DL, Ekdahl KN, Meri S | title = Complement C3b interactions studied with surface plasmon resonance technique | journal = International Immunopharmacology | volume = 1 | issue = 3 | pages = 495–506 | date = March 2001 | pmid = 11367533 | doi = 10.1016/S1567-5769(00)00042-4 }}

Biologically active Factor H has been produced by Ralf Reski and coworkers in the moss bioreactor,{{cite journal | vauthors = Büttner-Mainik A, Parsons J, Jérôme H, Hartmann A, Lamer S, Schaaf A, Schlosser A, Zipfel PF, Reski R, Decker EL | title = Production of biologically active recombinant human factor H in Physcomitrella | journal = Plant Biotechnology Journal | volume = 9 | issue = 3 | pages = 373–383 | date = April 2011 | pmid = 20723134 | doi = 10.1111/j.1467-7652.2010.00552.x | doi-access = free }} in a process called molecular farming. Large quantities of biologically active human Factor H, potentially suitable for therapeutic purposes, were produced using a synthetic codon-optimised gene expressed in the yeast expression host, Pichia pastoris.{{cite journal | vauthors = Schmidt CQ, Slingsby FC, Richards A, Barlow PN | title = Production of biologically active complement factor H in therapeutically useful quantities | journal = Protein Expression and Purification | volume = 76 | issue = 2 | pages = 254–263 | date = April 2011 | pmid = 21146613 | pmc = 4067574 | doi = 10.1016/j.pep.2010.12.002 }}

{{Reflist|33em}}

{{refbegin|33em}}

• {{cite journal | vauthors = Bradley DT, Zipfel PF, Hughes AE | title = Complement in age-related macular degeneration: a focus on function | journal = Eye | volume = 25 | issue = 6 | pages = 683–693 | date = June 2011 | pmid = 21394116 | pmc = 3178140 | doi = 10.1038/eye.2011.37 }}
• {{cite journal | vauthors = Kardys I, Klaver CC, Despriet DD, Bergen AA, Uitterlinden AG, Hofman A, Oostra BA, Van Duijn CM, de Jong PT, Witteman JC | title = A common polymorphism in the complement factor H gene is associated with increased risk of myocardial infarction: the Rotterdam Study | journal = Journal of the American College of Cardiology | volume = 47 | issue = 8 | pages = 1568–1575 | date = April 2006 | pmid = 16630992 | doi = 10.1016/j.jacc.2005.11.076 | doi-access = free }}
• {{cite journal | vauthors = Pío R, Elsasser TH, Martínez A, Cuttitta F | title = Identification, characterization, and physiological actions of factor H as an adrenomedullin binding protein present in human plasma | journal = Microscopy Research and Technique | volume = 57 | issue = 1 | pages = 23–27 | date = April 2002 | pmid = 11921353 | doi = 10.1002/jemt.10047 | s2cid = 37608883 | doi-access = free }}
• {{cite journal | vauthors = Walport MJ | title = Complement. First of two parts | journal = The New England Journal of Medicine | volume = 344 | issue = 14 | pages = 1058–1066 | date = April 2001 | pmid = 11287977 | doi = 10.1056/NEJM200104053441406 }}
• {{cite journal | vauthors = Walport MJ | title = Complement. Second of two parts | journal = The New England Journal of Medicine | volume = 344 | issue = 15 | pages = 1140–1144 | date = April 2001 | pmid = 11297706 | doi = 10.1056/NEJM200104123441506 }}

{{refend}}

• [https://www.ncbi.nlm.nih.gov/books/NBK1367/ GeneReviews/NCBI/NIH/UW entry on Atypical Hemolytic-Uremic Syndrome]
• [https://www.ncbi.nlm.nih.gov/books/NBK1425/ GeneReviews/NCBI/NIH/UW entry on Dense Deposit Disease/Membranoproliferative Glomerulonephritis Type II]
• [https://www.ncbi.nlm.nih.gov/omim/277400,120700,120920,134370,134371,138470,188040,217030,235400,605336,605337,612922,612923,612924,612925,612926,120700,120920,134370,134371,138470,188040,217030,235400,605336,605337,612922,612923,612924,612925,612926 OMIM entries on Atypical Hemolytic-Uremic Syndrome]
• {{MeshName|Complement+Factor+H}}

{{PDB Gallery|geneid=3075}}

{{Complement system}}

{{Beta globulins}}

Category:Complement system