Lutheran System: Anti-Lua

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

Key points

  • Anti-Lua is rarely clinically significant.
  • Patients with anti-Lua should receive red blood cell units crossmatch compatible by IAT at 37°C for transfusion.
  • Patients with sickle cell disease who have anti-Lua should be provided with Lua-negative red blood cell units for transfusion.

Background

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.

Patient management: Pre-transfusion and prenatal 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.

Patients with sickle cell disease

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.

Table 1: Red blood cell transfusion for patients with non-ABO antibodies

Patient Antibody Recommendation for red blood cell transfusion*
Diego system
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
Kell system
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
Lewis system
Anti-Lea, Anti- Leb, and Anti-Lea Red blood cell units crossmatch compatible by IAT at 37°C
Lutheran system
Anti-Lua Red blood cell units crossmatch compatible by IAT at 37°C
MNS system
Anti-M Red blood cell units crossmatch compatible by IAT or equivalent using IgG antihuman globulin
Rh system
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.

Suggested citation

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

Resources

1.    Davis BA, Allard S, Qureshi A, et al. Guidelines on red cell transfusion in sickle cell disease. Part I: principles and laboratory aspects. Br J Haematol. 2016;176(2):145-330. Available from: http://www.b-s-h.org.uk/guidelines/guidelines/red-cell-transfusion-in-sickle-cell-disease-part-l/
2.    Garratty G, Dzik W, Issitt PD, Lublin DM, Reid ME, Zelinski T. Terminology for blood group antigens and genes-historical origins and guidelines in the new millennium. Transfusion. 2000;40(4):477-89.
3.    NHS Blood and Transplant. NHSBT: Specification SPN214/3: The Clinical Significance of Blood Group Alloantibodies and the Supply of Blood for Transfusion. Available from: https://nhsbtdbe.blob.core.windows.net/umbraco-assets-corp/14863/spn2144-the-clinical-significance-of-blood-group-alloantibodies-and-the-supply-of-blood-for-transfusion.pdf
4.    Parsons SF, Lee G, Spring FA, et al. Lutheran blood group glycoprotein and its newly characterized mouse homologue specifically bind alpha5 chain-containing human laminin with high affinity. Blood. 2001;97(1):312-20.
5.    Reid M, Lomas Francis C and Olsson M. The Blood Group Antigens Facts Book, 3rd ed. San Diego: Elsevier Science & Technology; 2012. Section II: The blood group systems and antigens; Lutheran Blood Group System, Lua antigen. p. 270-2.
6.    The Canadian Haemoglobinopathy Association. Transfusion. In: Consensus Statement on the Care of Patients with Sickle Cell disease in Canada. Version 2.0. Ottawa; 2018. p. 12-20. Available from: https://www.canhaem.org/wp-content/uploads/2018/05/Sickle-Cell-Consensus.pdf
7.    Daniels G. Human Blood Groups, 3rd ed. Oxford: Wiley-Blackwell; 2013. Chapter 6, Lutheran Blood Group System, 6.3.4.1 Anti-Lua. p. 263.