Immunohematology Journal of Blood Group Serology and Education Volume 26, Number 4, 2010 Immunohematology Journal of Blood Group Serology and Education Volume 26, Number 4, 2010 Contents Review 133 Polylactosamines, there’s more than meets the “Ii”: a review of the I system L. Cooling Original Report 156 Attempts to support an immune etiology in 800 patients with direct antiglobulin test–negative hemolytic anemia R.M. Leger, A. Co, P. Hunt, and G. Garratty Review 161 The pathophysiology and prevention of transfusion-related acute lung injury (TRALI): a review D.C. Mair and T. Eastlund Original Report 174 Comparison of gel test and conventional tube test for antibody detection and titration in D-negative pregnant women: study from a tertiary care hospital in North India M.K. Thakur, N. Marwaha, P. Kumar, S.C. Saha, B. Thakral, R.R. Sharma, K. Saluja, H.K. Dhawan, and A. Jain Review 178 The Rh and RhAG blood group systems S.T. Chou and C.M. Westhoff Communication 187 Letter to the editors Anti-Vel and cold-reactive autoantibody Communication 188 Letter from the editors Thank you to the contributors of the 2010 issues 189 Index — Volume 26, Nos. 1, 2, 3, 4, 2010 193 Announcements 195 Advertisements 199 Instructions For Authors Editor-in-Chief Editorial Board Sandra Nance, MS, MT(ASCP)SBB Philadelphia, Pennsylvania Patricia Arndt, MT(ASCP)SBB Paul M. Ness, MD Pomona, California Baltimore, Maryland Managing Editor James P. AuBuchon, MD Joyce Poole, FIBMS Cynthia Flickinger, MT(ASCP)SBB Seattle, Washington Bristol, United Kingdom Philadelphia, Pennsylvania Martha R. Combs, MT(ASCP)SBB Mark Popovsky, MD Durham, North Carolina Braintree, Massachusetts Senior Medical Editor Geralyn M. Meny, MD Geoffrey Daniels, PhD Marion E. Reid, PhD, FIBMS Bristol, United Kingdom New York City, New York Philadelphia, Pennsylvania Anne F. Eder, MD S. Gerald Sandler, MD Technical Editors Washington, District of Columbia Washington, District of Columbia Christine Lomas-Francis, MSc George Garratty, PhD, FRCPath Jill R. Storry, PhD New York City, New York Pomona, California Lund, Sweden Dawn M. Rumsey, ART (CSMLT) Brenda J. Grossman, MD David F. Stroncek, MD Glen Allen, Virginia St. Louis, Missouri Bethesda, Maryland Christine Lomas-Francis, MSc Associate Medical Editors New York City, New York Emeritus Editorial Board Delores Mallory, MT(ASCP) SBB David Moolten, MD Gary Moroff, PhD Supply, North Carolina Philadelphia, Pennsylvania Rockville, Maryland Ralph R. Vassallo, MD John J. Moulds, MT(ASCP)SBB Philadelphia, Pennsylvania Shreveport, Louisiana Editorial Assistant Immunohematology is published quarterly (March, June, September, and December) by the Sheetal Patel American Red Cross, National Headquarters, Washington, DC 20006. Immunohematology is indexed and included in Index Medicus and MEDLINE on the MEDLARS Copy Editor system. The contents are also cited in the EBASE/Excerpta Medica and Elsevier BIOBASE/Current Mary L. Tod Awareness in Biological Sciences (CABS) databases. The subscription price is $40.00 (U.S.) and $50.00 (foreign) per year. Proofreader Subscriptions, Change of Address, and Extra Copies: Lucy Oppenheim Immunohematology, P.O. Box 40325 Philadelphia, PA 19106 Production Assistant Marge Manigly Or call (215) 451-4902 Web site: www.redcross.org/immunohematology Electronic Publisher Copyright 2010 by The American National Red Cross Paul Duquette ISSN 0894-203X On Our Cover “Les yeux clos” (1889–1905), Odilon Redon Odilon Redon created several versions of Les yeux clos (Closed Eyes) between 1889 and 1905. The striking radiance of the woman’s face hints at both the mystery and the significance of inner vision. With her eyes shut, she is unable to see the world, but because the eyes are so central to human identity, the world is also unable to truly see her. Is she asleep or dead? What are her dreams, her thoughts? The subject of the painting was Redon’s wife, although he may have also been inspired by a Michelangelo sculpture of a dying Roman slave. The Ii blood group is the subject of a review article in this issue, which provides insight into the clinical and basic science of polylactosamines. ——DAVID MOOLTEN, MD Review Polylactosamines, there’s more than meets the “Ii”: a review of the I system L. Cooling Key Words: polylactosamine, I blood group, cold agglutinins mutations in the I gene, IGnT (GCNT2).7–10 Serologic studies of family members, who presumably are heterozygous, History can have an intermediate I+i+ phenotype with elevated i The unofficial birth of the I blood group system can and weakened I expression relative to normal controls.2,11 1 be traced to a seminal case report in 1956. Wiener and In certain kindreds, iadult is associated with congenital colleagues at New York University and Jewish Hospital cataracts.12–14 Based on older serologic studies, the 1,15 reported a fatal case of cold agglutinin syndrome caused by a incidence of iadult ranges from 1 in 4400 to 1 in 17,000. The potent autoantibody they named “anti-I” for “individuality.” prevalence of mutant IGnT alleles in the general population The patient was a 62-year-old woman with a 5-year history is unknown but is presumably rare. of anemia and episodes of acute life-threatening hemolysis. Increased i expression can be observed with several Although the patient’s serum was compatible with donor inherited and acquired hemolytic disorders as a sign of RBCs at 37°C, she had periodic acute hemolytic transfusion stressed erythropoiesis. Increased i expression is found reactions with “compatible” RBCs, even after warming the on reticulocytes, and also occurs in megaloblastic anemia, blood before transfusion. In an attempt to provide compatible erythroleukemia, thalassemia, paroxysmal nocturnal blood, the patient’s serum was eventually tested against hemoglobinuria, and other hemolytic disorders.16–18 family members, 22,000 blood donors, and an assortment Increased i is also a common finding in hereditary of animals including rabbit, sheep, horse, and cow. A total of erythroblastic multinuclearity with positive acidified five compatible donors were eventually identified, and their serum lysis test (HEMPAS) disease, a rare hematopoietic RBCs were successfully transfused to the patient during the disorder characterized by dyserythropoiesis, altered RBC next 2 years. Because these donors appeared to lack I, their glycosylation, and hemolysis.19 Unlike other hemolytic RBCs were designated i phenotype. In a desperate moment disorders, the increased i observed on HEMPAS RBCs when “compatible” human blood was unavailable, the patient reflects abnormal Golgi trafficking and glycosylation.20,21 was transfused with cow blood, which had demonstrated only weak activity at 4°C. Not surprisingly, the transfusion Biochemistry was aborted within 10 minutes, after the patient developed Ii Structure anxiety, acute dyspnea, and feelings of “impending doom”! I and i are structurally and biosynthetically related The serologic relationship between I and i phenotypes oligosaccharide chains, composed of repeating units was solidified with the identification of an anti-i by Dr. of N-acetyllactosamine (Fig. 1; [Galβ14GlcNAcβ1-] , Lawrence Marsh.2 The antibody was strongly reactive with n LacNAc). I and i are ubiquitously expressed on human cord RBCs and i RBCs but not normal adult RBCs. More adult tissues and membrane structures. On RBC glycoproteins, importantly, Marsh was able to demonstrate a progressive polylactosamines are expressed as asparagine- or N-linked age-dependent decrease in i on infant RBCs, suggesting a glycans, ranging from biantennary to large, polyvalent developmental relationship between I and i. tetraantennary structures (Fig. 1B). On gut, leukocytes, Ii System and other tissues, polylactosamine may also be expressed As noted by Marsh, I and i are developmentally regulated as O-linked glycans via covalent linkages on serine and antigens on RBCs. At birth, cord RBCs serologically type as threonine residues (Fig. 1C). Polylactosamines are also I–i+. A discernible increase in I expression is observed by 3 found on membrane glycosphingolipids (Fig. 1A), including months, accompanied by parallel decreases in i expression, massive polyglycosylceramides ranging from 20 to 50 with an adult-type I+ phenotype observed by 18 months.2 carbohydrate residues in size.22 Increases in I mirror increases in ABO expression, which Structurally, i is defined as a linear, unbranched type typically reach adult levels by 2 to 3 years of age (see section 2 chain structure bearing at least two successive LacNAc on HDFN).3 Using human anti-I sera, the number of available residues (Fig. 1A).23 I is a branched polylactosamine derived I sites is estimated to be anywhere from 30,000 to 140,000 from i by the addition of a β1,6-linked polylactosamine side on untreated adult RBCs,4–6 but increases nearly threefold chain.23 Antibodies against I, therefore, must recognize after enzyme treatment (see section on Ii antibodies).6 GlcNAcβ16Galβ-R as part of the immune epitope.23,24 The iadult phenotype is a rare, autosomal-recessive trait Although I is often depicted with binary, terminal β13 and characterized by an absence of I on RBCs as a result of β16 LacNAc epitopes, in reality, β1,6 branching can occur IMMUNOHEMATOLOGY, Volume 26, Number 4, 2010 133 L. Cooling Fig. 1 Structures of Ii oligosaccharides on cell membranes. (A) Structure of i-active and I-active glycosphingolipid (N-acetyl ceramide). Endo-ß-endoceramidase can cleave i-active oligosaccharides; however, I-active oligosaccharides are resistant. (B) Structure of biantennary and tetraantennary glycans on N- or asparginine-linked glycoproteins. (C) O-glycan structures. (D) Terminal modification of Ii or type 2 chain oligosaccharides. Cer = ceramide; Gal = galactose; GalNAc = N-acetylgalactosamine; Glc = glucose; GlcNAc = N-acetylglucosamine; Man = mannose. anywhere along the polylactosamine backbone, assuming such as ABO, LeX, sLeX, LeY, and sialo-Ii activity (Fig. the presence of at least two successive LacNAc residues (see 1D).27 On human RBCs, more than 95 percent of all ABO later section).