Complement System

The complement system is part of the innate immune system and plays an important role in the host defense, inflammation, tissue regeneration and other physiological processes. Complement activation results in opsonization of pathogens and their removal by phagocytes. It also causes chemotactic attraction of phagocytes and macrophages. Furthermore, the complement system forms the terminal attack complex (MAC), a membrane channel causing osmotic lysis of the respective pathogen. While complement is not adaptable it does complement the adaptive immune system and it is also involved in B and T cell response regulation.

Activation of complement unfolds along three different complement activation pathways depending on the nature of the pathogen: the classical pathway, the lectin pathway, and the alternative pathway. All three converge into the common terminal pathway that leads to the formation of the MAC. In addition, anaphylatoxins C3a and C5a elicit a plethora of physiological responses that range from chemoattraction to apoptosis. The complement system consists of more than 30 proteins that are either present as soluble proteins in the blood or as membrane-associated proteins. Most exist as inactive zymogens that are then sequentially cleaved and activated. The central component in all three pathways is component C3, the most abundant complement protein found in the blood. Its activation induces the formation of the activation products C3a, C3b, and C5a and ultimately the MAC.

In addition to these three established pathways, it has been shown that factors such as kallikrein, plasmin, thrombin, and factor XIIa activate the complement system independently of the C3 protein.

In COVID-19, the SARS-CoV-2 nucleocapsid protein protein triggers activation of the lectin pathway of the complement system through interaction with mannose binding lectin (MBL)-associated serine protease (MASP)2. Released soluble N protein dimers interact with MASP-2, further accelerating MASP-2 activation and activation of the complements system. The positive feedback through cell lysis and release of N-protein leads to elevation of pro-inflammatory cytokines, characterized as cytokine storm.

N-protein neutralization is a promising avenue for a COVID-19 therapy, as well as the targeted inhibition of MASP-2. Suppressive effects could also be observed with anti-C5a antibody treatment.

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  1. Gao T, et al. (2020): "Highly pathogenic coronavirus N protein aggravates lung injury by MASP-2-mediated complement over-activation" medRxiv, [DOI: 10.1101/2020.03.29.20041962v2]
  2. Risitano AM, et al., (2020): “Complement as a target in COVID-19?” Nature Reviews Immunology, 65(12): 1337-45 [DOI: 10.1038/s41577-020-0320-7]

Classical Pathway

C1QA (Complement Component 1, Q Subcomponent, A Chain):

C1QB (Complement Component 1, Q Subcomponent, B Chain):

C1QC (Complement Component 1, Q Subcomponent, C Chain):

C1R (Complement Component 1, R Subcomponent):

Antigens in this category:

Lectin Pathway

MASP2 (Mannan-Binding Lectin serine Peptidase 2):

The Ra-reactive factor (RARF) is a complement-dependent bactericidal factor that binds to the Ra and R2 polysaccharides expressed by certain enterobacteria. Alternate splicing of this gene results in two transcript variants encoding two RARF components that are involved in the mannan-binding lectin pathway of complement activation. The longer isoform is cleaved into two chains which form a...   More...
Antigens in this category:
MASP1 (Mannan-Binding Lectin serine Peptidase 1 (C4/C2 Activating Component of Ra-Reactive Factor)): MASP1 antibodies MASP1 ELISA Kits MASP1 Proteins
MBL2 (Mannose-Binding Lectin (Protein C) 2, Soluble): MBL2 antibodies MBL2 ELISA Kits MBL2 Proteins
FCN1 (Ficolin (Collagen/fibrinogen Domain Containing) 1): FCN1 antibodies FCN1 ELISA Kits FCN1 Proteins
FCN2 (Ficolin (Collagen/fibrinogen Domain Containing Lectin) 2 (Hucolin)): FCN2 antibodies FCN2 ELISA Kits FCN2 Proteins
FCN3 (Ficolin (Collagen/fibrinogen Domain Containing) 3 (Hakata Antigen)): FCN3 antibodies FCN3 ELISA Kits FCN3 Proteins

Alternative Pathway

CFB - Complement Factor B

CFD - Adipsin

Antigens in this category:
C3 (Complement Component 3): C3 antibodies C3 ELISA Kits C3 Proteins
C3b - Complement Fragment 3b:      
CFH - Complement Factor H: CFH antibodies CFH ELISA Kits CFH Proteins

Terminal Pathway

C5 - Complement Component 5

The protein encoded by this gene is the fifth component of complement, which plays an important role in inflammatory and cell killing processes. This protein is comprised of alpha and beta polypeptide chains that are linked by a disulfide bridge. An activation peptide, C5a, which is an anaphylatoxin that possesses potent spasmogenic and chemotactic activity, is derived from the alpha...   More...
Antigens in this category:
C5a - C5A: C5a antibodies C5a ELISA Kits C5a Proteins
C7 (Complement Component C7): C7 antibodies C7 ELISA Kits C7 Proteins
C8A (Complement Component 8, alpha Polypeptide): C8A antibodies C8A ELISA Kits C8A Proteins
C8B (Complement Component 8, beta Polypeptide): C8B antibodies C8B ELISA Kits C8B Proteins
C8G (Complement Component 8, gamma Polypeptide): C8G antibodies C8G ELISA Kits C8G Proteins
C9 (Complement Component C9): C9 antibodies C9 ELISA Kits C9 Proteins


CD55 (Complement Decay-Accelerating Factor):

CD59 (CD59):

Antigens in this category:
SERPING1 (Serpin Peptidase Inhibitor, Clade G (C1 Inhibitor), Member 1): SERPING1 antibodies SERPING1 ELISA Kits SERPING1 Proteins
CFI - Complement Factor I: CFI antibodies CFI ELISA Kits CFI Proteins
CR1 (Complement Component Receptor 1 (CD35)): CR1 antibodies CR1 ELISA Kits  
CFP (Complement Factor P): CFP antibodies CFP ELISA Kits CFP Proteins
C4BPA (Complement Component 4 Binding Protein, alpha): C4BPA antibodies C4BPA ELISA Kits C4BPA Proteins
C4BPB (Complement Component 4 Binding Protein, beta): C4BPB antibodies C4BPB ELISA Kits C4BPB Proteins

Extrinsic Pathway

F2 - Prothrombin

Coagulation factor II is proteolytically cleaved to form thrombin in the first step of the coagulation cascade which ultimately results in the stemming of blood loss. F2 also plays a role in maintaining vascular integrity during development and postnatal life. Mutations in F2 leads to various forms of thrombosis and dysprothrombinemia. [provided by RefSeq, Jul 2008].   More...
Antigens in this category:
PLG (Plasminogen): PLG antibodies PLG ELISA Kits PLG Proteins
KLK1 - Kallikrein 1: KLK1 antibodies KLK1 ELISA Kits KLK1 Proteins
KLK2 - Kallikrein 2: KLK2 antibodies KLK2 ELISA Kits KLK2 Proteins
PSA - Prostate Specific Antigen: PSA antibodies PSA ELISA Kits PSA Proteins
KLKB1 (Kallikrein B, Plasma (Fletcher Factor) 1): KLKB1 antibodies KLKB1 ELISA Kits KLKB1 Proteins
KLK4 - Kallikrein 4: KLK4 antibodies KLK4 ELISA Kits KLK4 Proteins
KLK5 - Kallikrein 5: KLK5 antibodies KLK5 ELISA Kits KLK5 Proteins
KLK6 - Kallikrein 6: KLK6 antibodies KLK6 ELISA Kits KLK6 Proteins
KLK7 - Kallikrein 7: KLK7 antibodies KLK7 ELISA Kits KLK7 Proteins
KLK8 - Kallikrein 8: KLK8 antibodies KLK8 ELISA Kits KLK8 Proteins
KLK9 - Kallikrein 9: KLK9 antibodies KLK9 ELISA Kits KLK9 Proteins
KLK10 - Kallikrein 10: KLK10 antibodies KLK10 ELISA Kits KLK10 Proteins
PRSS57 (Protease, Serine, 57):     PRSS57 Proteins
KLK11 - Kallikrein 11: KLK11 antibodies KLK11 ELISA Kits KLK11 Proteins
KLK12 - Kallikrein 12: KLK12 antibodies KLK12 ELISA Kits KLK12 Proteins
KLK13 - Kallikrein 13: KLK13 antibodies KLK13 ELISA Kits KLK13 Proteins
KLK14 - Kallikrein 14: KLK14 antibodies KLK14 ELISA Kits KLK14 Proteins
KLK15 - Kallikrein 15: KLK15 antibodies   KLK15 Proteins
F12 - Coagulation Factor XII (Hageman Factor): F12 antibodies F12 ELISA Kits F12 Proteins