Authors: Danielle Meunier, MD; Sophia Peng, MD; and Gwen Clarke, MD, FRCPC
Publication date: September 2019
Primary target audiences: Medical laboratory technologists (MLT) in a hospital laboratory, transfusion medicine physicians
Lua is an antigen of the Lutheran blood group system. It is one of 20 Lutheran antigens on two conserved red blood cell surface glycoproteins known as Lutheran (Lu) and basal cell adhesion molecule (BCAM). Lu/BCAM is a part of the immunoglobulin superfamily of receptors that differ from one another only in their intracellular domain. They are high-affinity receptors for laminin, an extracellular matrix protein integral to the basement membrane of all cells. Lu/BCAM is known to be overexpressed on sickle red cells and thought to contribute to circulatory stasis and vaso-occlusive episodes by facilitating erythrocyte adhesion to vascular endothelial cells.
Anti-Lua was first described in 1945 in a patient with lupus erythematosus (who also produced anti-Cw, anti-c, and anti-Kpc). It is named after the red blood cell donor, although it was later discovered that the donor’s name was actually Lutteran but had been misspelled as Lutheran on the sample tube.
Among the relatively uncommon antibodies against Lutheran antigens, Anti-Lua is the most common, which is why Lua positive cells are typically included in screening panels. Anti-Lua is usually an immune-stimulated antibody (i.e. stimulated by transfusion or pregnancy-related red blood cell exposure) but may also occur naturally, often in association with other antibodies. It is usually an IgM antibody but may have some associated IgG and IgA components. As such, most anti-Lua will directly agglutinate red blood cells at room temperature as well as in the 37°C IAT phase. Also, as Lu/B-CAM is heterogeneously expressed on red cells, antibodies may display a mixed-field agglutination on testing.
In the context of transfusion, anti-Lua is rarely clinically significant for most patients. It does not contribute to acute hemolytic transfusion reactions and is very rarely associated with mild, delayed hemolytic transfusion reactions and mild hemolytic disease of the fetus and newborn (HDFN). With respect to HDFN, fetal Lua is often present on placental tissues; consequently, adsorption of maternal IgG antibodies onto placental cells prevents antibody transfer to the fetus. This has no apparent impact on pregnancy viability.
When anti-Lua is detected in a patient’s pre-transfusion sample, there is usually no requirement for selection of Lua-negative donor red blood cells. In fact, 92% of donor units are Lua-negative. Routine donor antigen typing (phenotyping) at Canadian Blood Services does not include Lua typing, therefore a request for Lua-negative red blood cell units results in additional manual phenotyping and/or genotyping. For current and historic anti-Lua, red blood cell units that are crossmatch compatible in the 37°C IAT phase should be selected for transfusion. See Table 1 for a summary of recommendations for red blood cell transfusion in patients with non-ABO antibodies.
For sickle cell disease patients without antibodies, most guidelines recommend transfusion of Rh- and Kell-matched units. For those patients with one or more antibodies (current or historical), complete donor phenotype/genotype matching is often recommended. Typically, this matching includes the Rh, Kell, Kidd and Duffy blood group systems along with the S/s antigens. If a patient with sickle cell disease develops an anti-Lua, then Lua-negative units should be provided, along with matching for the full phenotype, as above. Given the increased risk of hyperhemolysis in patients with sickle cell disease, this clinical context necessitates full compatibility with the patient’s antigen and antibody profile whenever possible.
|Patient Antibody||Recommendation for red blood cell transfusion*|
|Anti-Dia||Red blood cell units crossmatch compatible by IAT at 37°C|
|Anti-Wra||Red blood cell units crossmatch compatible by IAT at 37°C|
|Anti-Jsa||Jsa-negative red blood cell units crossmatch compatible by IAT at 37°C|
|Anti-Kpa||Red blood cell units crossmatch compatible by IAT at 37°C|
|Anti-Lea, Anti- Leb, and Anti-Lea||Red blood cell units crossmatch compatible by IAT at 37°C|
|Anti-Lua||Red blood cell units crossmatch compatible by IAT at 37°C|
|Anti-M||Red blood cell units crossmatch compatible by IAT or equivalent using IgG antihuman globulin|
|Anti-Cw||Red blood cell units crossmatch compatible by IAT at 37°C|
|Anti-V||V-negative red blood cell units crossmatch compatible by IAT at 37°C|
* Note: Patients with sickle cell disease who develop any one of the antibodies listed here should be provided with antigen-negative red blood cell units for transfusion.
For an introduction to immunohematology and the foundations of blood bank compatibility testing, visit LearnSerology.ca, an online educational resource developed by transfusion medicine specialists in Canada. The curriculum consists of six modules and includes an interactive module for completing an antibody investigation panel.
Meunier D, Peng S, Clarke G. Lutheran system: Anti-Lua [Internet]. Ottawa: Canadian Blood Services; 2019 Sept 25 [cited YYYY MM DD]. Available from: https://profedu.blood.ca/en/transfusion/best-practices/serological-best-practices