Related Experiment Video

Updated: Jul 5, 2026

High-resolution Melting PCR for Complement Receptor 1 Length Polymorphism Genotyping: An Innovative Tool for Alzheimer's Disease Gene Susceptibility Assessment
07:26

High-resolution Melting PCR for Complement Receptor 1 Length Polymorphism Genotyping: An Innovative Tool for Alzheimer's Disease Gene Susceptibility Assessment

Published on: July 18, 2017

Depressed activation of the lectin pathway of complement in hereditary angioedema

L Varga1, G Széplaki, J Laki

  • 13rd Department of Internal Medicine, Semmelweis University, Hungarian Academy of Sciences, Budapest, Hungary. lvarga@kut.sote.hu

Clinical and Experimental Immunology
|May 8, 2008
PubMed

Insights

This study shows that the lectin pathway (LP) of complement activation may occur in hereditary angioedema (HAE) patients with C1-inhibitor (C1INH) deficiency, indicated by lower MASP-2 and C4 levels. This finding offers new insights into complement system dysregulation in HAE.

Area of Science:

  • Immunology
  • Complement System Biology
  • Genetic Disorders

Background:

  • Hereditary angioedema (HAE) is characterized by C1-inhibitor (C1INH) deficiency and complement system dysregulation.
  • The Wielisa method enables simultaneous measurement of classical pathway (CP), mannan-binding lectin (MBL)-lectin pathway (LP), and alternative pathway (AP) complement activation.
  • Understanding the in vivo role of C1INH across all three complement pathways is crucial for HAE research.

Purpose of the Study:

  • To investigate the in vivo significance of C1-inhibitor (C1INH) in the CP, LP, and AP of complement activation.
  • To compare complement pathway activities and associated protein levels in HAE patients versus healthy controls.
  • To explore the relationship between MBL-2 genotypes and LP activity in HAE patients.

Main Methods:

  • Simultaneous measurement of CP, LP, and AP functional activity using the Wielisa method in 68 HAE patients and 64 healthy controls.
  • Quantification of C1q, MBL, MASP-2, C4, C3, and C1INH levels using standard laboratory assays.
  • Determination of MBL-2 genotypes via polymerase chain reaction.

Main Results:

  • HAE patients exhibited lower CP and C1INH activity, and reduced C4 and C1INH concentrations compared to controls.
  • MASP-2 levels were significantly lower in HAE patients (P = 0.0001).
  • Depressed LP activity was observed in HAE patients with the normal MBL genotype (A/A) (P = 0.0008), but not in those with variant genotypes.
  • CP and LP activity correlated in HAE patients (r = 0.64; P < 0.0001), while CP and AP correlated in controls (r = 0.47; P < 0.0001).

Conclusions:

  • The lectin pathway (LP) may be activated in individuals with C1INH deficiency, as suggested by low MASP-2 and C4 levels.
  • Complement pathway interactions differ between HAE patients and healthy individuals.
  • These findings highlight potential LP involvement in the pathophysiology of HAE.

More Related Videos

Methods for Quantitative Detection of Antibody-induced Complement Activation on Red Blood Cells06:29

Methods for Quantitative Detection of Antibody-induced Complement Activation on Red Blood Cells

Published on: January 29, 2014

Related Concept Videos

Complement System01:27

Complement System

The complement system is a group of approximately 20 plasma proteins that strengthen the body's defenses against infections through opsonization, inflammation, and cell lysis. Opsonization involves coating pathogens with complement proteins, making them more recognizable and facilitating phagocyte engulfment. Certain complement proteins induce inflammation that attracts immune cells to the site of infection. Cell lysis involves the destruction of pathogens through the formation of a membrane...
Cytotoxic Edema: Pathophysiology01:21

Cytotoxic Edema: Pathophysiology

Cytotoxic edema is a form of cerebral edema characterized by intracellular swelling of neurons, astrocytes, and other glial cells. It develops when the mechanisms responsible for maintaining ionic gradients across the cell membrane become impaired. Under normal physiological conditions, the sodium–potassium ATPase actively transports sodium ions out of the cell and potassium ions into the cell, preserving osmotic balance and enabling electrical signaling. This pump requires a continuous supply...
Selectins01:25

Selectins

Cell adhesion is  an essential aspect of multicellularity. While stable cell interactions usually occur between cells of the same type, transient cell interactions occur between cells of different tissue types, such as between neutrophils and endothelial cells. Selectins are one class of cell adhesion molecules (CAMs) that bind carbohydrate ligands to form transient cell adhesion. They are rod-like proteins with a long extracellular part of variable length ending with the lectin domain, which...
Cerebral Edema ll: Pathophysiology01:22

Cerebral Edema ll: Pathophysiology

Vasogenic edema is a major form of cerebral edema characterized by abnormal accumulation of fluid in the brain’s extracellular space due to disruption of the blood–brain barrier (BBB). The BBB is a specialized structure composed of endothelial cells connected by tight junctions, supported by astrocytic endfeet and a basement membrane. Under normal conditions, it tightly regulates the movement of ions, proteins, and solutes between the bloodstream and brain parenchyma. When this barrier loses...
Lysosomal Hydrolases01:22

Lysosomal Hydrolases

Lysosomes are the site for the degradation of macromolecules and biological polymers released during membrane trafficking events such as secretory, endocytic, autophagic, and phagocytic pathways. The membrane-enclosed area of the lysosome, called the lumen, contains hydrolytic enzymes active in an acidic environment. These acid hydrolases are functional at a pH between 4.5 and 5 and are involved in cellular processes such as cell signaling, energy metabolism, restoration of the plasma membrane,...
Antihypertensive Drugs: Angiotensin-Converting Enzyme Inhibitors01:30

Antihypertensive Drugs: Angiotensin-Converting Enzyme Inhibitors

Angiotensin-converting enzyme (ACE), a vital component of the renin-angiotensin-aldosterone system, is abundant in lung endothelial cells. ACE converts the inactive decapeptide, angiotensin I, into the active octapeptide, angiotensin II. This potent vasoconstrictor narrows blood vessels, increasing resistance to blood flow and elevating blood pressure. Angiotensin II also stimulates aldosterone production, encouraging kidney cells to reabsorb more sodium and water from urine, thereby increasing...