B LOOD G ROUP R EVIEW An update on the Lewis blood group system M.R. Combs This update of the Lewis blood group system (Combs MR. Lewis chills, severe back pain, hemoglobinuria, and increased levels blood group system review. Immunohematology 2009;25:112–8) of bilirubin, alanine transaminase, and serum creatinine. A describes new information on the clinical significance of Lewis monocyte monolayer assay, testing the patient’s serum with antigens regarding susceptibility of individuals to certain diseases and the possible role of bacteria in Lewis expression. This update the Le(a+) RBCs causing the reaction, was positive also describes recently reported examples of Lewis antibodies A case report in 2015 of a possible HTR due to anti-Lea causing hemolytic transfusion reactions. No new antigens have was reported in a pregnant patient with sickle cell disease with been identified in the International Society of Blood Transfusion a 10 system 7, leaving the antigen count to stand at six: Lea, Leb, LebH, a 37°C gel-reactive anti-Le . The crossmatch was compatible ALeb, BLeb, and Leab. Immunohematology 2019;35:65–66. using prewarmed plasma neutralized with Lewis substance. During transfusion, the patient experienced significant Key Words: Lewis, fucosyltransferases, antigen, antibody dyspnea, hypotension, and hemoglobinuria. Indirect bilirubin and lactate dehydrogenase tests were elevated. The direct Lewis Antigens antiglobulin test on the post-transfusion sample was negative, indicating the possibility that all incompatible RBCs were Lewis antigen fucosyltransferases are encoded by the cleared. FUT3 gene located on chromosome 19p13.3.1 The presence or A case of an HTR due to anti-Leb, also in 2015, was absence of Lewis antigens in an individual can be associated reported.11 A pretransfusion sample from a 30-year-old with the individual’s susceptibility to certain diseases and African-American woman showed a negative antibody infections. As described in a recent review,2 non-secretors detection test in solid phase. Nine days after receipt of two are more likely than secretors [Le(b+)] to be susceptible to computer crossmatch-compatible RBC units, her hemoglobin symptomatic cholera,3 bacterial meningitis,4 type 2 diabetes dropped to 7.9 g/dL. The post-transfusion sample typed as mellitus,5 and type 1 diabetes mellitus.6 In addition, increased group B, D+, although agglutination with the reagent B RBCs activity of the secretor and Lewis fucosyltransferases seems to in the reverse grouping was detected and thought to be a cold be involved in the development and control of cancers of the agglutinin. Electronic crossmatch-compatible RBC units were distal colon.2 issued. During infusion, the patient developed signs of an acute A recent review7 discusses the possible role of bacteria in HTR (chills, nausea, brown urine). An in vitro hemolytic IgM Lewis expression. The intestinal tract switches from sialylated anti-Leb was identified. A tube test–only, room temperature– glycans to fucosylated antigens with age and bacterial reactive anti-Lea was also identified. colonization.8 It is speculated that the low Leb expression on neonatal red blood cells (RBCs) reflects the immature nature References of gut flora.7 1. Combs MR. Lewis blood group system review. Immunohematology 2009;25:112–8. Lewis Antibodies 2. Ewald D, Sumner S. Blood type biochemistry and human disease. Wiley Interdiscip Rev Syst Biol Med 2016;8:517–35. Lewis antibodies are usually clinically insignificant and 3. Arifuzzaman M, Ahmed T, Rahman MA, et al. Individuals with Le(a+b–) blood group have increased susceptibility are rarely associated with hemolytic transfusion reactions to symptomatic Vibrio cholera O1 infection. PLoS NTDS (HTRs). Three recent reports of Lewis antibodies associated 2011;5:e1413. with HTRs have been reported. 4. Blackwell CC, Jonsdottir K, Weir DM, et al. Blood group, secretor status and susceptibility to bacterial meningitis. A case report from 2013 describes a severe HTR due to FEMS Microbiol Immunol 1989;1:351–6. a 9 anti-Le in a multiply transfused Le(a–b–) patient. After 5. Greenwell P. Blood group antigens: molecules seeking a receipt of a crossmatch-compatible Le(a+) RBC unit, the function? Glycoconj J 1997;14:159–73. patient developed an acute transfusion reaction with fever, IMMUNOHEMATOLOGY, Volume 35, Number 2, 2019 65 M.R. Combs 6. Smyth DJ, Cooper JD, Howson JM, et al. FUT2 nonsecretor 10. Duncan V, Pham H, Williams L III. A possible case of a status links type 1 diabetes susceptibility and resistance to haemolytic transfusion reaction caused by anti-Lea antibody. infection. Diabetes 2011;60:3081–4. Blood Transfus 2015;13:535–6. 7. Cooling L. Blood groups in infection and host susceptibility. 11. Irani MS, Figueroa D, Savage G. Acute hemolytic transfusion Clin Microbiol Rev 2015;28:801–70. reaction due to anti-Leb. Transfusion 2015;55:2486–8. 8. Nanthakumar NN, Dai D, Newburg DS, Walker WA. The role of indigenous microflora in the development of murine intestinal Martha Rae Combs, MT(ASCP)SBB, Technical Director of fucosyl- and sialyltransferases. FASEB J 2003;17:44–6. Immunohematology Reference Laboratory, Duke Hospital 9. Höglund P, Ragnhild R-L, Wikman AT. A severe haemolytic Transfusion Service, Room 1720, Box 2928, 2301 Erwin Road, transfusion reaction caused by anti-Lea active at 37°C. Blood Transfus 2013;11:456–9. Durham, NC 27710, [email protected]. 66 IMMUNOHEMATOLOGY, Volume 35, Number 2, 2019.