ICAM4
Encyclopedia
The LW blood system was first described by Landsteiner
and Weiner in 1940. It was often confused with the Rh
system, not becoming a separate antigen system until 1982. The LW and RhD antigens are genetically independent though they are phenotypically related and the LW antigen is expressed more strongly on RhD positive cells than on RhD negative cells. In most populations, the antithetical LW antigens, LWa and LWb are present as very high and very low frequency, respectively.
red cell membrane glycoprotein
named CD242. The LW glycoprotein has recently been renamed ICAM-4 due to its similarity to intercellular adhesion molecule
, although exactly which integrins bind to ICAM-4 is subject to controversy.
The function of ICAM-4 is not fully understood but appears to be restricted to erythroid cells. During in vitro erythropoesis, LW appears at either the erythroid colony forming stage or later at the proerythroblast stage. A vital part of erythropoesis is the clustering of erythroblasts around bone marrow
macrophages to form erythroblastic islands. The erythroblast is then able to remove its nucleus
, which is in turn ingested and broken down by the macrophages, to become a mature erythrocyte. During this process ICAM-4 binds to VLA-4, an erythroblast binding site, on adjacent erythroblasts and to αv integrins on macrophages to help stabilise the erythroblastic islands. The binding of red cells to macrophages in the spleen by ICAM-4 could also play a part in the removal of senescent red cells.
Despite the functional aspects of ICAM-4, its apparent absence in LW(a-b-) and Rhnull phenotypes does not appear to lead to any obvious pathological effects. ICAM-4 expression is elevated on sickle red cells and its binding to αv integrins on the endothelial cells may cause the pain associated with sickle cell crises.
Auto anti-LW is not uncommon as an autoantibody
but usually presents with transient suppression of the LW antigen in genetically LW+ individuals, and so appears to be an alloantibody. True alloanti-LW is a very rare occurrence, with only two known examples of alloanti-LWab, produced by patients with an LW(a-b-) phenotype. Anti-LW can be present as a clinically insignificant autoantibody and not be associated with increased red cell destruction. Anti-LW has also been associated with cases of warm type autoimmune haemolytic anaemia; Levine suggested that it was the most common antibody in cases of AIHA with a positive Coombs test
.
Landsteiner
Landsteiner:* Leopold Landsteiner , a 19c. Austrian publicist* Karl Borromäus Landsteiner , Austrian Catholic theologian, author* Karl Landsteiner , an Austrian Jewish chemist and physician**...
and Weiner in 1940. It was often confused with the Rh
RH
RH, Rh, rH, or rh can stand for:* Riemann hypothesis, an important unsolved problem in mathematics* Ryan's Hope, a soap opera* Rhesus factor, a classification to describe blood types in humans* Rhodium, a chemical element...
system, not becoming a separate antigen system until 1982. The LW and RhD antigens are genetically independent though they are phenotypically related and the LW antigen is expressed more strongly on RhD positive cells than on RhD negative cells. In most populations, the antithetical LW antigens, LWa and LWb are present as very high and very low frequency, respectively.
Molecular biology
LW antigens reside on a 40- to 42-kiloDaltonDalton
Dalton may refer to:-In Canada:* Dalton, Algoma District, Ontario* Dalton Armoury, a Canadian Forces facility primarily used by the Queen's Own Rifles of Canada- In the United Kingdom :* Dalton, Cumbria, England* Dalton, Dumfries and Galloway, Scotland...
red cell membrane glycoprotein
Glycoprotein
Glycoproteins are proteins that contain oligosaccharide chains covalently attached to polypeptide side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycosylation. In proteins that have segments extending...
named CD242. The LW glycoprotein has recently been renamed ICAM-4 due to its similarity to intercellular adhesion molecule
Intercellular adhesion molecule
Intercellular adhesion molecules are members of the family of cell adhesion molecules. They include the following:* ICAM-1 * ICAM2* ICAM3* ICAM4* ICAM5...
, although exactly which integrins bind to ICAM-4 is subject to controversy.
The function of ICAM-4 is not fully understood but appears to be restricted to erythroid cells. During in vitro erythropoesis, LW appears at either the erythroid colony forming stage or later at the proerythroblast stage. A vital part of erythropoesis is the clustering of erythroblasts around bone marrow
Bone marrow
Bone marrow is the flexible tissue found in the interior of bones. In humans, bone marrow in large bones produces new blood cells. On average, bone marrow constitutes 4% of the total body mass of humans; in adults weighing 65 kg , bone marrow accounts for approximately 2.6 kg...
macrophages to form erythroblastic islands. The erythroblast is then able to remove its nucleus
Cell nucleus
In cell biology, the nucleus is a membrane-enclosed organelle found in eukaryotic cells. It contains most of the cell's genetic material, organized as multiple long linear DNA molecules in complex with a large variety of proteins, such as histones, to form chromosomes. The genes within these...
, which is in turn ingested and broken down by the macrophages, to become a mature erythrocyte. During this process ICAM-4 binds to VLA-4, an erythroblast binding site, on adjacent erythroblasts and to αv integrins on macrophages to help stabilise the erythroblastic islands. The binding of red cells to macrophages in the spleen by ICAM-4 could also play a part in the removal of senescent red cells.
Despite the functional aspects of ICAM-4, its apparent absence in LW(a-b-) and Rhnull phenotypes does not appear to lead to any obvious pathological effects. ICAM-4 expression is elevated on sickle red cells and its binding to αv integrins on the endothelial cells may cause the pain associated with sickle cell crises.
Auto anti-LW is not uncommon as an autoantibody
Autoantibody
An autoantibody is an antibody manufactured by the immune system that is directed against one or more of the individual's own proteins. It is derived from the Greek "auto" which means "self", "anti" which means "against" and "body"...
but usually presents with transient suppression of the LW antigen in genetically LW+ individuals, and so appears to be an alloantibody. True alloanti-LW is a very rare occurrence, with only two known examples of alloanti-LWab, produced by patients with an LW(a-b-) phenotype. Anti-LW can be present as a clinically insignificant autoantibody and not be associated with increased red cell destruction. Anti-LW has also been associated with cases of warm type autoimmune haemolytic anaemia; Levine suggested that it was the most common antibody in cases of AIHA with a positive Coombs test
Coombs test
Coombs test refers to two clinical blood tests used in immunohematology and immunology...
.