Hereditary Angioneurotic Edema Health Article

Definition

Hereditary angioneurotic edema (HANE) is a nonsex linked (autosomal) dominant disease that results from mutations in a gene responsible for producing one of the proteins responsible for human immunity. This disease is also known as hereditary angioedema (HAE) or hereditary C1 inhibitor deficiency because it is a deficiency of the protein (C1-INH) that inhibits the action of the enzyme known as C1 which causes this disease.

Description

There are two recognized forms of HANE. Type I represents approximately 80-85% of the cases of hereditary angioneurotic edema. In this type, the protein C1-INH is not produced in sufficient quantities. Type II HANE represents the remaining 15-20% of cases. In this type, C1-INH concentrations are normal, but the C1-INH protein produced is defective.

Related to the two types of hereditary angioneurotic edema are acquired types of this disease (AANE or AAE) that are not based on a defective gene. Type I AAE is caused by a disorder that causes over-growth (proliferation) of the lymph tissues and destroys C1-INH. Type II AAE is caused by the presence of auto-antibodies (antibodies that attack the host organism that produced them) that destroy C1-INH. Both of these acquired forms of angioedema can generally be differentiated from the two types of HANE by the age of onset. Symptoms of the acquired diseases usually do not occur until the fourth decade of life, while those of the hereditary forms are generally present prior to puberty.

The human body has two distinct immune systems: the humoral immune system and the cell-mediated immune system. The complement system is a part of the humoral immune system. Humoral means within the humor, or fluids, of the body. Blood, lymph, and bile compose the fluids of the humor. The complement system uses at least 30 different proteins to "mark" any foreign cells in the body that do not have certain protective proteins on their cell membranes which identify them as belonging in the body. These complement proteins are designated C1, C2, C3, et cetera. Once the foreign cells have been "marked," a particular form of white blood cell, called a phagocyte, is dispatched to the area with the marked cells and destroys them.

Phagocytes will eventually destroy any cell that is marked by complement; therefore, it is important to make sure that the complement proteins are not marking non-foreign cells. When cells are improperly marked, these cells will also be destroyed, causing what is called an autoimmune response. In effect, this autoimmune response means that the body is recognizing itself as foreign and attempting to destroy healthy cells. Inhibitors of the various complement proteins are necessary to prevent these proteins from marking the wrong cells or from continuing to mark cells after the foreign cells have been destroyed.

C1 inhibitor (C1-INH) is a chemical that is involved in the regulation of the complement system by inhibiting the action of the first complement protein (C1). C1-INH acts by binding free C1 molecules in the humor, preventing them from being able to function. It also limits the activation of other complement proteins.

Because C1-INH is diminished or defective in people affected with HANE, C1 is not inhibited and this inappropriately initiates the complement reaction which causes the swelling (acute inflammatory response) characteristic of HANE.

C1-INH also binds to the chemicals kallikrein and plasmin that are involved in blood clotting. Kallikrein is necessary for the activation of chemicals that cause dilation of blood vessels to allow increased blood flow to an area that requires more blood than normal. Plasmin is the chemical responsible for dissolving blood clots. A lack of binding of plasmin means that the formation of initial blood clots is difficult, a problem that is exacerbated by high levels of unbound kallikrein, which allows higher than normal blood flow.

With the absence or dysfunction of the C1-INH protein, the functions of blood flow, blood clotting, and immune response are impaired in individuals affected by hereditary angioneurotic edema, leading to swelling of the bodily tissues.