A review: the Kidd system R. MOUGEY After the rediscovery of the principle of the an- The antibody is not thought to be merely anti-Jk sup(a) + tiglobulin test and its introduction as the direct or in- anti-Jksup(b), because immunized Jk(a- b - ) individuals make direct "Coombs" test, there was a period of rapid anti-Jk3 whether they are sensitized by the Jksup(a) or Jk sup(b) discovery of new blood group systems that were im- antigen. Also the sera of Jk(a-b-) individuals often portant to blood transfusion therapy. One of the most contain a separable anti-Jksup(a) or -Jksup(b) component. Since important was the recognition of the Kidd blood group no individual has yet been found that is Jk(a+) or Jk(b+) system in 1951.sup(1) The patient, a Mrs. Kidd, had a new and Jk: - 3, the anti-Jk3 is thought to recognize a shared antibody in her serum and gave birth to an infant with determinant that is on all red cells of common Jk hemolytic disease of the newborn (HDN). The antibody phenotypes. The most recent evidence in support of was named anti-Jksup(a) The "J" was added to avoid con- the Jk3 antigen is the discovery of persons who are fusion with the Kell antigen. In retrospect, this case phenotypically Jk(a -b - ), Jk:3.5 of HDN is a curiosity since Kidd antibodies do not There is some controversy about the expression of typically cause significant HDN.sup(2) Other examples were theJk3 antigen in the presence of the Jk gene. Humphrey quickly discovered, and the expected anti-Jksup(b) was found and Morelsup(6) found a normal expression of the Jk3 in 1953 by Plaut et al.3 Although the discovery of the antigen in persons of Jk sup(a)Jk or Jk sup(b)Jk genotype even null phenotype [F(a-b-)]sup(4) and the ability of Kidd anti- though the same persons demonstrated the expected bodies to demonstrate dosage mirrored findings in other weaker Jksup(a) orJk sup(b) antigen strength. This effect was not blood group systems in the 1950s, no other Kidd system noted by Pierce et al.7 in a study of a family with the antigens of low frequency or high frequency have been Jk gene. This discrepancy may be related to difficulties discovered. The significant aspect of the Kidd system in the preparation of pure anti-Jk3 by absorption and remains its ability to cause hemolytic transfusion reac- elution or to differences in antibody titration methods. tions. The purpose of this review is to describe the recent It is not yet known whether the genes controlling discoveries in the genetics and biochemistry of the Kidd the expression of the Kidd antigens code for a protein system and to review its importance in blood bank or act on a precursor. The association of the Kidd serology, transfusion reactions, HDN, and autoimmune antigens with the urea transport protein make it more hemolytic anemia. likely that they are epitopes on a basic protein, and that the presence of the Jksup(a)Jk3 or Jksup(b)Jk3 antigens are Genetics necessary for normal urea and water transport in The inheritance of the Kidd genes and their aqueous urea solutions.sup(8) The rapid progress currently phenotypic expression are shown in Table 1. Anti-Jk3 being made in blood group biochemistry and molecular refers to the antibody formed by those individuals of genetics makes it seem likely that these puzzles will the Jk(a-b-) phenotype commonly known as Jksub(null) soon be resolved. Table 1 Phenotypic expression in the Kidd system and frequencies of the phenotype in selected populations Tests with Adult phenotype frequencies (%) anti-Jksup(a) anti-Jk sup(b) Anti-Jk3 Phenotype Whites' Blacks sup(9) Orientalssup(10,11) + 0 + Jk(a+b-) 26.3 51.1 23.22 + + + Jk(a+b+ ) 40.3 50.3 49.94 0 + + Jk(a -b + ) 23.4 8.1 26.84 0 0 0 Jk(a-b-) <0.01 <0.01 .9 to <.l VOLUME 6, NUMBER 1, 1990 1 R. MOUGEY In red cell typings of disputed parentage cases, the appeared to be Jksub(null). However, when the red cells were Kidd system is fairly useful, with an exclusion rate of tested with anti-Jk3, the individuals and their apparent 0.19 in whites and 0.16 in blacks.sup(9) Although the silent Jk sub(null) siblings were found to react weakly with anti- Jk. gene is known to exist in whites, its highest frequency Jk3, and their red cells also absorbed and eluted anti- is seen in certain Oriental populations. This means Jksup(a) or -Jksup(a), as shown by the italicized phenotypes in that the presence of a silent allele may cause a false Fig. 2. exclusion in a paternity case. It is extremely important to use a second-order exclusion in the Kidd system as an indicator that additional exclusions should be searched for in other systems. A more common diffi- Jk(a+b-) Jk(a+b-) Jk(a+b-) Jk(a+b-) culty with Kidd antigen typings is obtaining quantities of reliable anti-Kidd sera. It is tempting to use the rare examples of potent anti-Kidd sera from patients instead of commercial reagents, but few laboratories have the expertise to ensure the purity and potency of such sera. Occasionally, very weak positive reactions are found Jk(a-b-) Jk(a-b-) Jk(a+b-) even with commercial reagents. In 1980, Boyd stud- ied this problem with anti-Jksup(b) antisera to determine if Fig. 1. Kidd phenotypes of part of the Rob demonstrating that theJk gene behaves as a true amorphic gene. Strength of antigen there was a qualitative difference among Jksup(b) antigens determined by titration studies. but was unable to demonstrate such a difference (un- published observation cited in Issittsup(12)). Problems such heterozygotes for Jksup(a) as these can be a cause of serious errors in Kidd typ- homozygotes for Jksup(a) homozygotes for Jk ings and should he recognized by those who perform and those who supervise such typings. Family studies of Jksub(null) individuals, such as the one shown in Fig. 1, have demonstrated that the Jk gene behaves as a true amorphic gene. All parents of Jk sub(null) individuals that have been tested have been phenotypically either Jk(a-b+) or Jk(a+b-), and all offspring of Jk sub(null) persons that have been tested have also been either Jk(a+b-) or Jk(a-b+). The family shown in Fig. 1 is part of the Rob family reported by Habibi et al. l3 This was the first example of a Cauca- sian Jk sub(null) individual; a second family was found by Klarkowskisup(14) and a third by Sistonensup(15) in Finland. All other Jksub(null) persons were of Oriental descent; most were Jk(a-b-) Jk(a-b-) Jk(a-b-) Jk(a-b+) found because they had formed anti-Jk3. Jksup(a)/Jk sup(a) Jksup(a)/Jk sup(a) Jksup(b)/Jk sup(b) However, a very important discovery by Heaton and Fig. 2. Part of the YS family5 showing suppression of Kidd gene McLoughlinsup(16) has made it possible to screen large expression by the InJk gene. The phenotypes in italics were numbers of donors for the Jk sub(null) phenotype very demonstrated using absorption, elution studies. economically. They noted that the red cells of a presence of In(Jk); tested as Jk(a-h-) using Jk(a-b-) patient did not lyse in 2M urea, but shrank agglutination method. and were counted as platelets by an automated instru- ment. This observation has also led to biochemical The inheritance of a dominant suppressor of Kidd studies of the Kidd antigen (see below) and to the finding antigens is similar to the InLu gene, and the authors of a suppressor gene affecting the Kidd antigen expres- have named the gene InJk. None of the six persons with sion in two Japanese families. Okubo and his co- the InJk phenotype has made anti-Jk3, perhaps because workers5 were using 2M urea lysis to screen for like the InLu Lu(a- b-) individuals, their antigens are Jk(a-b-) blood donors and found two individuals who too weak to be detected except by absorption and 2 I M M U N O HEM AT O L O G Y The Kidd system elution. It has not yet been determined if there are any Thus, at present, no non-red cell line is thought to have other blood group systems that are depressed by the the Kidd blood group antigens, nor are the antigens InJk gene. secreted into plasma, saliva, urine, or breast milk. Chromosome assignment Kidd antigen modification Over the years, the Kidd locus has been reported to It appears that products of bacterial cultures such as be on chromosome7sup(17) or 2;sup(18) however, these tentative Proteus mirubilis and Streptococcus faecium have the assignments have been refuted by additional studiessup(19,20) ability to alter the Kidd phenotypes of red cells. In a and Kidd is now thought to be on chromosome 18. report in 1979, McGinniss et al.sup(27) described an unusual Geitvik and co-workerssup(21) have determined that the case in which a patient expressed autohemolysis due Kidd locus is closely linked to a restriction fragment to anti-Jksup(b) only during an active urinary tract infection length polymorphism (RFLP) defined by the genomic with P.