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.   


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