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Complement System Solutions for Drug Development and Clinical Research
January 6, 2015

Complement System Solutions for Drug Development and Clinical Research

Datasheet: Complement System Immunoassays Download
The complement system is essential to innate immunity which protects from chronic, autoimmune, and infectious disease. There are three distinct pathways of complement activation: classical, lectin/MBL, and alternative. Each leads to the generation of the same set of effector molecules which help eliminate infections and pathogens. The initiation of each pathway is dependent upon different molecules. In addition to kits that measure activation of each pathway individually or on a single plate (Total Functional Screen), ALPCO now offers two novel assays to measure Factor P. Factor P, also known as Properdin, has an important role in the amplification loop of the complement system. Upon binding to C3bBb, it acts as a stabilizer, extending the half-life of C3bBb significantly. In addition, it inhibits the factor H-mediated cleavage of C3b by factor I, thereby increasing C3b formation and positively regulating the complement cascade response. Assays to measure biomarkers C4d and Terminal Complement Complex (TCC) are also available. The Complement TCC ELISA measures the concentration of TCC (sC5b-9) levels in human plasma; an essential step to evaluate whether foreign materials in contact with blood trigger an immune response. The Complement TCC ELISA reflects complement activation regardless of pathway. C4d is a well-published biomarker for activation of the Classical and Lectin/MBL Pathways. The C4d ELISA targets a unique neoepitope to eliminate cross-reactivity, a problem in other commercial assays, and also tests for both A and B genetic variants. The importance of the complement system has become evident in both clinical research and drug development. Activity biomarkers help determine whether deficiencies, overactivation, or dysregulation in the complement system are causing, or contributing to, a person's disease or condition.

Analyzing complement activity helps researchers:

  • Look for deficiencies that result in infections
  • Follow disease activity and improve treatment regimens for complement-related disorders
  • Investigate the potency of new complement-targeted therapies
  • Monitor complement function and activity of drug candidates
  • Discover off-target complement reactions caused by drug candidates

Complement System Immunoassays

ALPCO offers assays to explore every angle of complement system-involvement in a wide range of application areas based on ELISA technology.  Our complement assays offer a unique and complete assessment of all three pathways. Testing may be conducted simultaneously, saving time and effort, or individually.  In the Total Complement Functional Screen ELISA, the sample is co-incubated with a specific blocker to ensure that only the desired pathway is activated, securing accurate results.

Available Complement System ELISAs

Item Catalog Number Datasheet
Classical Pathway ELISA 13-COMPL-CP310
Alternative Pathway ELISA 13-COMPL-AP330
Lectin/MBL Pathway ELISA 13-COMPL-MP320
Total Complement Functional Screen ELISA 13-COMPL-300
Complement C4d ELISA 13-COMPL-C4d Download
Complement Factor P Functional ELISA 13-COMPL-FPF
Complement Factor P Quantitative ELISA 13-COMPL-FPQ
Terminal Complement Complex (TCC) ELISA 13-COMPL-TCC Download
Anti-C4d Antibody 04-BI-RC4D
Anti human C4d (FITC Conjugated) 04-BI-RC4D-FITC

Key Features:

  • Reliable, easy-to-interpret results and short incubation
  • Low inter-assay variability and excellent reproducibility
  • Ready-to-use reagents and short incubation time streamline workflow
  • Excellent specificity means clear results without false positives
  • Only product to offer exploration of all three complement system pathways individually

Complement System Cascade

Complement System Cascade Resources & References

Complement System Webinar Presenter: Dr. Jorgen Wieslander PhD in Biochemistry, Lund University Post. Doc. at Dept. of Medical Biochemistry, Kansas University

References

Seelen MA et al. Functional analysis of the classical, alternative, and MBL pathways of the complement system: standardization and validation of a simple ELISA. J Immunol Meth 2005; 296: 187-198.

Tudoran R & Kirschfink M. Modern complement analysis: indications, methods and outlook. J Lab Med 2012;36.

Mollnes TE et al. Complement analysis in the 21st century. Mol Immunol 2007;44: 3838-3849. Open source.

Harboe M et al. Advances in assay of complement function and activation. Adv Drug Deliv Rev 2011.

Ceribelli A et al. Complement Cascade in Systemic Lupus Erythematosus Analyses of the Three Activation Pathways. Ann. N.Y. Acad. Sci. 2009; 1173: 427–434.

Testa S. et al; Interval extension of maintenance Eculizumab treatment in patients with atypical haemolytical uremic syndrome. Poster B5, 4TH International conference HUS-MPGNTTP and related disorders, 2013.

Janeway CA Jr et al. Immunobiology: The Immune System in Health and Disease. 2001; http://www.ncbi.nlm.nih.gov/books/NBK27100/.

Nilsson B, et al. Complement Diagnostics: Concepts, Indications, and Practical Guidelines. Clinical and Developmental Immunology, Volume 2012, Article ID 962702, 11 pages

Idorn T, et al. Anti-glomerular basement membrane glomerulonephritis and thrombotic microangiopathy in first degree relatives; a case report. BMC Nephrology 2012, 13:64

Prior N, et al. Development of a disease-specific quality of life questionnaire for adult patients with hereditary angioedema due to C1 inhibitor deficiency (HAE-QoL): Spanish multi-centre research project. Health and Quality of Life Outcomes 2012, 10:82

Bergseth G, et al. Artificial Surface-Induced Inflammation Relies on Complement Factor 5: Proof From a Deficient Person. Ann Thorac Surg. 2011 February ; 91(2): 527–533

Ilyias R, et al. High Glucose Disrupts Oligosaccharide Recognition Function Via Competitive Inhibition: A Potential Mechanism for Immune Dysregulation in Diabetes Mellitus. Immunobiology. 2011; 216(1-2): 126–131

Fridkis-Hareli M, et al. Design and development of TT30, a novel C3d-targeted C3/C5 convertase inhibitor for treatment of human complement alternative pathway-mediated diseases. BLOOD, 27 Oct. 2011, Vol. 118, No. 17

Castellano G, et al. Therapeutic Targeting of Classical and Lectin Pathways of Complement Protects from Ischemia-Reperfusion-Induced Renal Damage. The American Journal of Pathology, Vol. 176, No. 4, April 2010