Unraveling the mystery: Anti-Jk3 and its peculiarities
The Kidd (Jk) blood group system was named in 1951 for the infant (John Kidd) who was born with hemolytic disease of the newborn. The Kidd system consists of two antithetical antigens with varying expression (Jka and Jkb), and the high-incidence antigen (Jk3) that is found on all individuals’ red cells except for those with the rare Jk null phenotype. Antibodies against Kidd antigens are notorious for the ability to drop to undetectable levels and ‘hide’ and can be missed during antibody screening. The rare Kiddnull phenotype, Jk(a-b-), is found among individuals of Asian, Polynesian, and Finnish descent.1,2,3,4 A patient with this phenotype may develop anti-Jk3 that is reactive with a domain common to Jka and Jkb antigen.3,4
We reviewed four cases to demonstrate the common approach in identifying anti-Jk3. All patients had reactivity consistent with antibody against high prevalence-antigen; equal strength panreactivity with nonreactive autocontrol.1 Review of pertinent blood bank history revealed that all patients were pregnant and of either Asian or Polynesian descent. Only one patient had a previous RBC transfusion. Extended phenotyping revealed that all patients were Jk(a-b-) and thus, anti-JK3 was suspected. The presence of anti-Jk3 was proven by nonreactivity of plasma with Jk(a-b-) reagent RBCs.
After adsorption, two cases had underlying antibodies while the other two had none. One of two cases with underlying antibodies demonstrated the in vitro difficulties that may be encountered in anti-Jk3. The initial reference laboratory suspected presence of another antibody when the patient’s plasma reacted with rr Kiddnull RBCs. This prompted consultation with a second reference laboratory that found four nonreactive Kiddnull RBCs, confirming the presence of anti-Jk3. Potential allo-antibodies in this patient were examined closely. She has an R1R1 phenotype, and her plasma reacted with rr Kiddnull RBC. This indicates a possible presence of anti-c or anti-f. Using R1R1-adsorbed plasma, anti-c was ruled out and probable anti-f was identified.
The adsorption studies of the first laboratory also identified anti-Jkb using the ID-Micro Typing System™ (ID-MTS™) Gel Test while the other laboratory detected both anti-Jka and anti-Jkb using Peg-IAT and LISS-IAT. It is not uncommon for Kidd antibody to react variably.3 It reacts stronger in test modalities that has anti-C3 than reagents containing only anti-IgG.3 Some studies have demonstrated better detection in PEG-IAT and SPRCA than with IgG ID-MTS gel.5,6 In addition, titers can quickly decline and become serologically non-demonstrable. 3,4 This unreliable in vitro detectability is likely one of the grounds for delayed hemolytic transfusion reaction (DHTR) commonly associated with Kidd antibodies.3,4
Antibodies detected in immunohematology are unique. Familiarity with the prevalence and nuances of each blood group system can help resolve these cases, in addition to obtaining transfusion histories from hospitals that have treated the patient.
References:
1. Er LS, Bailey DJ. Identification of antibodies to red cell antigens. In: Cohn C, Delaney M, Johnson S, Katz L, Eds. Technical manual 20th ed. Bethesda, MD: AABB Press, 2020:410-3, 423-4
2. Yousuf R, Suria AA, Nurasyikin Y, Leong C. A rare case of anti-Jk3 antibody detected on pre-transfusion investigation. Indian J Hematol Blood Transfus 2014;30:208-10
3. Issit PD, Anstee DJ. Applied blood group serology. 4th ed. Montgomery Scientific Publications, 1998:655-68
4. Melland C, Nance S. Other blood systems and antigens. In: Cohn C, Delaney M, Johnson S, Katz L, Eds. Technical Manual. 20th ed. Bethesda, MD: AABB Press, 2020:370-2
5. de Castilho LM, Pellegrino J Jr, Bechelli APP, Le Pennec PY, Mendres N. Evaluation of recent techniques for detection of red blood cell antibodies in sera of reference samples, patients, pregnant women, and blood donors. J Clin Lab Anal 1996;10:250-6
6.Kay B, Poisson JL, Tuma CW, Shulman IA. Anti-Jka that are detected by solid-phase red blood cell adherence but missed by gel testing can cause hemolytic transfusion reactions. Transfusion 2016;56:2973-9
Authors
Written By
Desiree Joy Anne Talabong, MD, MT(ASCPi)
SUNY Downstate Health Science University/Kings County Hospital Center
Walter E. Kelley, DO, FCAP
Dr. Kelley serves as Medical Director for Biomedical Services in the Utah/Nevada, Idaho/Montana, and Colorado/Wyoming Regions of the American Red Cross. He provides medical oversight for blood donation and blood products manufacturing and distribution in Utah and throughout the Rocky Mountains. He also provides consultation to physicians for patients with complex transfusion needs and has a keen interest in the investigation of adverse events related to transfusion. He oversees in-patient and outpatient therapeutic apheresis in Utah and Montana, including red cell exchange for patients living with sickle cell disease for pediatric patients at Primary Children’s Hospital and for adult patients with sickle cell disease at numerous hospitals throughout Salt Lake City. He is the FACT Director for collections and cell processing for the independently accredited transplant program that supports transplant at the LDS Hospital Bone and Marrow Transplant program and the Nebraska Methodist Hospital. He provides autologous cell therapy collection for the treatment of prostate cancer in Utah, Idaho and Colorado. Dr. Kelley’s current research endeavors include serving as Principal Investigator for the American Red Cross-National Cell Therapy program, which provides mononuclear cells to research partners for the development and production of cellular therapies. He also oversees IRB approved cell processing for investigational cellular therapeutic product development. Dr. Kelley earned his Bachelor of Science degree in Food Science and Human Nutrition and minor in Zoology from the University of Florida and his Doctor of Osteopathic Medicine degree from Midwestern University’s Arizona College of Osteopathic Medicine. He completed his pathology residency and clinical chemistry fellowship at the University of Maryland where he focused on the treatment of sickle cell disease through red cell exchange by apheresis, under the supervision of Professor John Hess. He then served as a civilian in the US Public Health Service as a clinical fellow in the department of Transfusion Medicine at the Clinical Center of the National Institutes of Health under Nobel Laureate Harvey J. Alter, MD. Dr. Kelley has authored or co-authored over thirty book chapters, manuscripts, and abstracts.
