The Complement System

Evaluation of total complement function in human serum is an essential component of laboratory diagnostics of the human complement system. During recent years, established hemolytic assays for classical pathway and alternative pathway function, CH50 and AP50 assays, respectively, have been replaced in many diagnostic laboratories by ELISA assays. Next to an improved standardization, this assay platform also allows for functional analysis of the lectin pathway of complement. The present chapter describes the methodology of ELISA assays for assessment of the classical pathway, the alternative pathway, the MBLdependent lectin pathway, and the Ficolin-3-dependent lectin pathway of complement in clinical laboratory diagnostics.

[1]  B. Høgh,et al.  Different molecular events result in low protein levels of mannan-binding lectin in populations from southeast Africa and South America. , 1998, Journal of immunology.

[2]  P. Garred,et al.  Variation in FCN1 affects biosynthesis of ficolin-1 and is associated with outcome of systemic inflammation , 2012, Genes and Immunity.

[3]  D. Power,et al.  Human Factor H-related Protein 5 (FHR-5) , 2001, The Journal of Biological Chemistry.

[4]  Loreto Gesualdo,et al.  Genome-wide association study identifies susceptibility loci for IgA nephropathy , 2011, Nature Genetics.

[5]  P. Barlow,et al.  Association of factor H autoantibodies with deletions of CFHR1, CFHR3, CFHR4, and with mutations in CFH, CFI, CD46, and C3 in patients with atypical hemolytic uremic syndrome. , 2010, Blood.

[6]  Laura A. Hecker,et al.  Copy number variation in the complement factor H-related genes and age-related macular degeneration , 2011, Molecular vision.

[7]  Frcp,et al.  Identification of a mutation in complement factor H-related protein 5 in patients of Cypriot origin with glomerulonephritis , 2010, The Lancet.

[8]  P. Zipfel,et al.  Human complement factor H-related protein 4 binds and recruits native pentameric C-reactive protein to necrotic cells. , 2009, Molecular Immunology.

[9]  M. Ronaghi,et al.  Real-time DNA sequencing using detection of pyrophosphate release. , 1996, Analytical biochemistry.

[10]  Matthew C. Thomas,et al.  Rapid detection and antimicrobial resistance gene profiling of Yersinia pestis using pyrosequencing technology. , 2012, Journal of microbiological methods.

[11]  M. Mihlan,et al.  Molecular basis of C-reactive protein binding and modulation of complement activation by factor H-related protein 4. , 2010, Molecular immunology.

[12]  S. Gharbia,et al.  Single-nucleotide polymorphism-based differentiation and drug resistance detection in Mycobacterium tuberculosis from isolates or directly from sputum. , 2005, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[13]  A. Sjöholm,et al.  Functional analysis of the classical, alternative, and MBL pathways of the complement system: standardization and validation of a simple ELISA. , 2005, Journal of immunological methods.

[14]  T. Fujita,et al.  P35, an opsonic lectin of the ficolin family, in human blood from neonates, normal adults, and recurrent miscarriage patients. , 1999, Immunology letters.

[15]  Don H. Anderson,et al.  Extended haplotypes in the complement factor H (CFH) and CFH-related (CFHR) family of genes protect against age-related macular degeneration: characterization, ethnic distribution and evolutionary implications. , 2006, Annals of medicine.

[16]  Laura A. Hecker,et al.  Contribution of copy number variation in the regulation of complement activation locus to development of age-related macular degeneration. , 2009, Investigative ophthalmology & visual science.

[17]  T. Aitman,et al.  Acute Presentation and Persistent Glomerulonephritis Following Streptococcal Infection in a Patient With Heterozygous Complement Factor H–Related Protein 5 Deficiency , 2012, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[18]  Amy E. Weaver,et al.  Mutations in alternative pathway complement proteins in American patients with atypical hemolytic uremic syndrome , 2010, Human mutation.

[19]  R. Cantor,et al.  Association of Genetic Variants in Complement Factor H and Factor H-Related Genes with Systemic Lupus Erythematosus Susceptibility , 2011, PLoS genetics.

[20]  G. Remuzzi,et al.  Genetic analysis of the complement factor H related 5 gene in haemolytic uraemic syndrome. , 2007, Molecular immunology.

[21]  S. Hober,et al.  Pyrosequencing: history, biochemistry and future. , 2006, Clinica chimica acta; international journal of clinical chemistry.

[22]  S. Hagstrom,et al.  Genetic analysis of complement factor H related 5, CFHR5, in patients with age-related macular degeneration , 2009, Molecular vision.

[23]  T. Fujita,et al.  Polymorphisms in the FCN2 gene determine serum variation and function of Ficolin-2. , 2005, Human molecular genetics.

[24]  T. van der Poll,et al.  Complement deficiency states and associated infections. , 2011, Molecular immunology.

[25]  S. Thiel,et al.  Disease-causing mutations in genes of the complement system. , 2011, American journal of human genetics.

[26]  S. Thiel,et al.  Proteolytic Activities of Two Types of Mannose-Binding Lectin-Associated Serine Protease , 2000, The Journal of Immunology.

[27]  P. Hill,et al.  Factor H-related protein-5: a novel component of human glomerular immune deposits. , 2002, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[28]  J L McRae,et al.  Variations in the complement regulatory genes factor H (CFH) and factor H related 5 (CFHR5) are associated with membranoproliferative glomerulonephritis type II (dense deposit disease) , 2005, Journal of Medical Genetics.

[29]  M. Matsushita,et al.  A novel measurement method for activation of the lectin complement pathway via both mannose-binding lectin (MBL) and L-ficolin. , 2009, Journal of immunological methods.

[30]  D. Gale,et al.  Regulating complement in the kidney: insights from CFHR5 nephropathy , 2011, Disease Models & Mechanisms.

[31]  K. Okochi,et al.  Serum concentration of Hakata antigen, a member of the ficolins, is linked with inhibition of Aerococcus viridans growth. , 2002, Clinica chimica acta; international journal of clinical chemistry.

[32]  L. Truedsson,et al.  New procedure for the detection of complement deficiency by ELISA. Analysis of activation pathways and circumvention of rheumatoid factor influence. , 1993, Journal of immunological methods.

[33]  O. el-Maarri,et al.  Sensitive Determination of BRAF Copy Number in Clinical Samples by Pyrosequencing , 2011, Diagnostic molecular pathology : the American journal of surgical pathology, part B.

[34]  S. Meri,et al.  Factor H Binding as a Complement Evasion Mechanism for an Anaerobic Pathogen, Fusobacterium necrophorum1 , 2008, The Journal of Immunology.

[35]  Peter H. Sudmant,et al.  Diversity of Human Copy Number Variation and Multicopy Genes , 2010, Science.

[36]  M. Parker,et al.  Human Factor H-Related Protein 5 Has Cofactor Activity, Inhibits C3 Convertase Activity, Binds Heparin and C-Reactive Protein, and Associates with Lipoprotein 1 , 2005, The Journal of Immunology.

[37]  Ivana K. Kim,et al.  The NEI/NCBI dbGAP database: Genotypes and haplotypes that may specifically predispose to risk of neovascular age-related macular degeneration , 2008, BMC Medical Genetics.

[38]  L. Trouw,et al.  Complement activation by (auto-) antibodies. , 2011, Molecular immunology.

[39]  F. Sanger,et al.  DNA sequencing with chain-terminating inhibitors. , 1977, Proceedings of the National Academy of Sciences of the United States of America.

[40]  K. Kyriacou,et al.  Familial C3 glomerulopathy associated with CFHR5 mutations: clinical characteristics of 91 patients in 16 pedigrees. , 2011, Clinical journal of the American Society of Nephrology : CJASN.

[41]  K. Skjødt,et al.  Characterization of a polymorphism in the coding sequence of FCN3 resulting in a Ficolin-3 (Hakata antigen) deficiency state. , 2008, Molecular immunology.

[42]  C. Hack,et al.  Functional characterization of the lectin pathway of complement in human serum. , 2003, Molecular immunology.

[43]  P. Garred,et al.  Functional Analysis of Ficolin-3 Mediated Complement Activation , 2010, PloS one.

[44]  E. Goicoechea de Jorge,et al.  Dimerization of complement factor H-related proteins modulates complement activation in vivo , 2013, Proceedings of the National Academy of Sciences.

[45]  S. Thiel,et al.  An assay for the mannan-binding lectin pathway of complement activation. , 2001, Journal of immunological methods.