Further Evidence of Heterogeneity Within the Kidd Blood Group System A . J. HUMPHREY AND P. A. MOREL From the Irwin Memorial Blood Bank of rheSan Francisco Medical SocietjJ.Sun Francisco. California
Serological studies on blood of selected individuals show that red blood cells from individuals genetically Jka& and JkbJk give single dose agglutination reactions with anti-Jk' and anti-Jkb respectively, but react as strongly with anti-JkdJkbas do cells from random individuals. A Jk(a+b-) Oriental person has been found whose red blood cells give a single dose reaction with anti-Jka, but react more weakly than do cells from random people b in tests with anti-Jk'Jk . T h e results support a conclusion that the antigen recognized by anti-JkaJkhis a distinct and separate antigen of the Kidd blood group system.
sera in the absence of detectable Jk" o r Jkb antigen. This report presents d a t a relating to quantitative studies with anti-Jk", anti-Jkb and anti-Jk'Jk', which suggest that the Jk"Jkb antigenic determinant of red blood cells also represents a distinct specificity in the Kidd blood group system. Serological Studies
All test and control cell samples in each tiT H EP H E N O T Y P E Jk(a-b-) in the Kidd blood tration experiment were collected and stored group system was first described by Pinkerunder similar conditions for the same period, ton, et al.' This and subsequent r e p ~ r t s * . ~ . ' ~ , "and tested in parallel by antiglobulin techattributed the occurrence of this phenotype nique allowing 45 minutes' incubation a t 37 C to the inheritance of a silent J k allele from in 22 per cent albumin dilutions of antiserum. each parent. The occurrence of the J k allele Each titration was scored by a hemagglutinain a heterozygous state (Jk'Jk o r J k h J k ) was tion scoring system modified from R a c e and demonstrated by Crawford, el who found Sangeru by Marsh.6 single dosage scores in titrations of such cells T h r e e anti-Jk" and two anti-Jkh sera were with anti-Jk"or anti-Jkb sera. used to confirm that the single dose effect deT h e antibody produced by immunized tected by others could be demonstrated. T a Jk(a-b-) individuals was called crossreacting ble 1 shows the results of tests with the red anti-Jk"Jkb since it reacted with both J k ( a + ) blood cells of the Jk"Jk person described by and J k ( b + ) red blood cell^.^.','^ S o m e of Crawford, et U I . and ~ Table 2 shows the rethese sera apparently also contained separasults with the red blood cells of the offble antibodies which demonstrated either spring of a Jk(a-b-) patient, Mrs. N. L., anti-Jk" or anti-Jkb specifi~ity.~.' A recent redescribed by Day, et u I . One ~ of the two antiport by Marsh et U I . describes ~ the occurJ k a J k b sera used in this study was serum rence on neutrophil leukocytes of the antifrom N . L., in which we were unable to demgenic determinant recognized by an ti-J k"J kb onstrate the previously separable anti-Jk" Received for publication April 28, 1975; accepted August 16, 1975.
component. In both cases, the results a r e consistent with the test cells having a heterozygous status in the Kidd blood group.
242 Transfusion
May-June 1976
Volume 16 Number 3
Volume 16 Number 3
243
HETEROGENEITY WITHIN T H E K l D D SYSTEM
In contrast, the high scores with antiJk"Jkb on all samples suggest either that this antigenic determinant is present in double dose or that the antibody lacks the capability of recognizing dosage. I n a further study, the anti-Jk"Jkb serum was titrated against red blood cells from Oriental blood donors of Jk(a+b-) and Jk(a-b+) phenotypes, seeking variations in antigen strength that may be recognized by the crossreacting sera. Orientals were chosen because the Jk(a-b-) phenotype appears to be of more frequent occurrence in this population.x Table 3 shows the results of testing 22 donors of apparent homozygous Kidd types. Similar results were obtained in tests with a second series of 21 Oriental donors. As shown in Table 4, one donor, J. D., was found whose red blood cells reacted less strongly with antiJk"Jkb and who may be heterozygous for the Jk"Jkb gene. Although nonreactive with three anti-Jkb sera, her cells also yielded single dose scores with three examples of anti-Jk".
Table 1. Titrations of M N C Red Blood Cells
Cell
Phenotype
Anti-Jka Score
Anti-JkaJkb Score
MNC Control Control
Jk(a+b-) Jk(a+b+) Jk(a+b-)
37 39 55
31 29 32
Table 2. Titrations of BL and D L Red Blood Cells
Cell
Phenotype
BL DL Control Control
Jk(a-b+) Jk(a-b+) J k(a+b+) Jk(a-b+)
Anti-Jkb Score
Anti-JkaJkb Score
40 37
39 34 40 42
34 59
Table 3. Titrations with Anti-JkaJkb
Phenotype
Number Tested
J k ( a +b- 1 Jk(a+b-) Jk (a +b+ ) Jk(a-b+)
JD 5 13
8
Scores 42-54 30 44-52 43-55
Discussion The data presented here do not refute sugTable 4. Titrations of JD Red Blood Cells gestions that the Jk(a-b-) phenotype arises Anti-Jka Anti-JkaJkb from the inheritance of a silent J k allele from Cell Phenotype Score Score each parent or that the presence of the silent Jk(a+b-) 46 30 allele can be detected indirectly by dosage JD Jk(a+b+) 52 51 studies with anti-Jk" or anti-Jkb. Our find- Control Control Jk(a+b-) 66 54 ings, however, provide further support to the conclusion that the antibody formed by an immunized Jk(a-b-) individual recognizes a or that a modifying gene may be depressing separate, distinct, and perhaps primary antiexpression of both J k " and Jk3. A study of gen in the Kidd system, which we suggest this donor's family was not possible. should be called Jk:3 in accordance with reOur studies with anti-Jk3 have provided cent nomenclature in other blood g r o u p ~ . ' * ~further evidence of complexity within the Reactivity of this primary antigen appears to Kidd blood group system, in demonstrating be unaffected when the controlling gene is that variation in expression on red blood cells present in the heterozygous state, but it is of the J k 3 gene on one hand, and the J k " and undetectable on the red blood cells of an indi- J k bgenes on the other, are not necessarily in vidual who is homozygous for a silent allele at harmony. this locus. The reduced expression of J k 3 detected on J. D.'s red blood cells, on the other References hand, appears to be affecting the normal exI . Allen, F. H., Jr., and R. E. Rosenfield: Notation pression of the J k a gene. It is possible that for the Kell blood-group system. Transfusion 1:305, 1961. she may have inherited only a single Jk" gene,
244 2.
3.
4.
5.
6. 7.
8.
HUMPHREY A N D MOREL Arcara, P. C., M. A. O’Connor, and R. M. Dimmette: A family with three Jk(a-b-) members. Transfusion 9:282, 1969. Crawford, M. N., T. J. Greenwalt, T. Sasaki, P. Tippett, R. Sanger, and R . R. Race: T h e phenotype Lu(a-b-) together with unconventional Kidd groups in one family. Transfusion 1:228, 1961. Day, D., H. A. Perkins, and B. Sams: The minusminus phenotype in the Kidd system. Transfusion5:315, 1965. Marsh, W. L., R. @yen, and M. E. Nichols: Kidd blood-group antigens of leukocytes and platelets. Transfusion 14:378, 1974. -: Scoring of hemagglutination reactions. Transfusion 12:352, 1972. Pinkerton, F. J., L. E. Mermod, B. A. Liles, J . A. Jack, and J. Noades: The phenotype Jk(a-b-) in the Kidd blood group system. Vox Sang. 4:155, 1959. Race, R. R., and R. Sanger: Blood Groups in Man, 5th ed. Oxford, Blackwell Scientific, 1968.
Transfusion May-June 1976
Rosenfield, R. E., F. H. Allen, Jr., S. N . Swisher, and S. Kochwa: A review of Rh serology and presentation of a new terminology. Transfusion 2:287, 1962. 10. Silver, R. T., J. M . Haber, and A. Kellner: Evidence for a new allele in the Kidd blood group system in indians of Northern Mato Grosso, Brazil. Nature 186:481, 1960. I I . Yokoyama, M., L. E. Mermod, and A. Stegmaier: Further examples of Jk(a-b-) blood in Hawaii. Vox Sang. 12:154, 1967. 9.
Arvilla J. Humphrey, B.S., MT(ASCP)SBB, Assistant Supervisor, General Laboratory, Irwin Memorial Blood Bank of the San Francisco Medical Society, 270 Masonic Avenue, San Francisco, California 941 18. Phyllis A. Morel, B.A., MT(ASCP)SBB, Supervisor, Reference Laboratory, Irwin Memorial Blood Bank of the San Francisco Medical Society, 270 Masonic Avenue, San Francisco, California 941 15. (Reprint requests).
First International Symposium on HLA and Disease An important international meeting will be held in Paris, France from June 23-25, 1976 on the topical subject of the relationship between HLA and Disease. During this first symposium on this subject, invited speakers will lecture on the basic principles (D. Shreffler, J . Klein, R. Payne, J . J . Van Rood, R. Ceppellini, C. A. Clarke), results already obtained ( A . Svejgaard, P. I. Terasaki), clinical implications (J. Dausset) and fundamental hypotheses explaining the associations ( R . Zinkernagel, W. F. Bodmer, D. B. Amos). Workshop sessions will bring together biologists and clinicians of every specialty: rheumatology (D. A . Brewerton, F. Delbarre), neurology (T. Fog, F. Lehermitte), dermatology (E. M . Farber, J. Civatte, J . Thivolet), endocrinology (J. Nerup, G. Cathelineau), gastroenterology (W. Strober, I. R. Mackay, J . P. Benhamou, J . Rey), allergy (A. d e Weck, M . N. Blumenthal) immunopathology (H. Kunkel, M . Seligmann), malignant diseases ( M . J . Simons, J. L. Amiel), other diseases (P. J . Morris, P. Royer). A special session will be devoted to a discussion of the possible mechanisms of associations between HLA and disease (H. 0. McDevitt, F. Jacob). For any information, please write to: Congres Services, I rue jules Lefebvre, 75009 Paris, France.
Serological studies on blood of selected individuals show that red blood cells from individuals genetically Jka& and JkbJk give single dose agglutination reactions with anti-Jk' and anti-Jkb respectively, but react as strongly with anti-JkdJkbas do cells from random individuals. A Jk(a+b-) Oriental person has been found whose red blood cells give a single dose reaction with anti-Jka, but react more weakly than do cells from random people b in tests with anti-Jk'Jk . T h e results support a conclusion that the antigen recognized by anti-JkaJkhis a distinct and separate antigen of the Kidd blood group system.
sera in the absence of detectable Jk" o r Jkb antigen. This report presents d a t a relating to quantitative studies with anti-Jk", anti-Jkb and anti-Jk'Jk', which suggest that the Jk"Jkb antigenic determinant of red blood cells also represents a distinct specificity in the Kidd blood group system. Serological Studies
All test and control cell samples in each tiT H EP H E N O T Y P E Jk(a-b-) in the Kidd blood tration experiment were collected and stored group system was first described by Pinkerunder similar conditions for the same period, ton, et al.' This and subsequent r e p ~ r t s * . ~ . ' ~ , "and tested in parallel by antiglobulin techattributed the occurrence of this phenotype nique allowing 45 minutes' incubation a t 37 C to the inheritance of a silent J k allele from in 22 per cent albumin dilutions of antiserum. each parent. The occurrence of the J k allele Each titration was scored by a hemagglutinain a heterozygous state (Jk'Jk o r J k h J k ) was tion scoring system modified from R a c e and demonstrated by Crawford, el who found Sangeru by Marsh.6 single dosage scores in titrations of such cells T h r e e anti-Jk" and two anti-Jkh sera were with anti-Jk"or anti-Jkb sera. used to confirm that the single dose effect deT h e antibody produced by immunized tected by others could be demonstrated. T a Jk(a-b-) individuals was called crossreacting ble 1 shows the results of tests with the red anti-Jk"Jkb since it reacted with both J k ( a + ) blood cells of the Jk"Jk person described by and J k ( b + ) red blood cell^.^.','^ S o m e of Crawford, et U I . and ~ Table 2 shows the rethese sera apparently also contained separasults with the red blood cells of the offble antibodies which demonstrated either spring of a Jk(a-b-) patient, Mrs. N. L., anti-Jk" or anti-Jkb specifi~ity.~.' A recent redescribed by Day, et u I . One ~ of the two antiport by Marsh et U I . describes ~ the occurJ k a J k b sera used in this study was serum rence on neutrophil leukocytes of the antifrom N . L., in which we were unable to demgenic determinant recognized by an ti-J k"J kb onstrate the previously separable anti-Jk" Received for publication April 28, 1975; accepted August 16, 1975.
component. In both cases, the results a r e consistent with the test cells having a heterozygous status in the Kidd blood group.
242 Transfusion
May-June 1976
Volume 16 Number 3
Volume 16 Number 3
243
HETEROGENEITY WITHIN T H E K l D D SYSTEM
In contrast, the high scores with antiJk"Jkb on all samples suggest either that this antigenic determinant is present in double dose or that the antibody lacks the capability of recognizing dosage. I n a further study, the anti-Jk"Jkb serum was titrated against red blood cells from Oriental blood donors of Jk(a+b-) and Jk(a-b+) phenotypes, seeking variations in antigen strength that may be recognized by the crossreacting sera. Orientals were chosen because the Jk(a-b-) phenotype appears to be of more frequent occurrence in this population.x Table 3 shows the results of testing 22 donors of apparent homozygous Kidd types. Similar results were obtained in tests with a second series of 21 Oriental donors. As shown in Table 4, one donor, J. D., was found whose red blood cells reacted less strongly with antiJk"Jkb and who may be heterozygous for the Jk"Jkb gene. Although nonreactive with three anti-Jkb sera, her cells also yielded single dose scores with three examples of anti-Jk".
Table 1. Titrations of M N C Red Blood Cells
Cell
Phenotype
Anti-Jka Score
Anti-JkaJkb Score
MNC Control Control
Jk(a+b-) Jk(a+b+) Jk(a+b-)
37 39 55
31 29 32
Table 2. Titrations of BL and D L Red Blood Cells
Cell
Phenotype
BL DL Control Control
Jk(a-b+) Jk(a-b+) J k(a+b+) Jk(a-b+)
Anti-Jkb Score
Anti-JkaJkb Score
40 37
39 34 40 42
34 59
Table 3. Titrations with Anti-JkaJkb
Phenotype
Number Tested
J k ( a +b- 1 Jk(a+b-) Jk (a +b+ ) Jk(a-b+)
JD 5 13
8
Scores 42-54 30 44-52 43-55
Discussion The data presented here do not refute sugTable 4. Titrations of JD Red Blood Cells gestions that the Jk(a-b-) phenotype arises Anti-Jka Anti-JkaJkb from the inheritance of a silent J k allele from Cell Phenotype Score Score each parent or that the presence of the silent Jk(a+b-) 46 30 allele can be detected indirectly by dosage JD Jk(a+b+) 52 51 studies with anti-Jk" or anti-Jkb. Our find- Control Control Jk(a+b-) 66 54 ings, however, provide further support to the conclusion that the antibody formed by an immunized Jk(a-b-) individual recognizes a or that a modifying gene may be depressing separate, distinct, and perhaps primary antiexpression of both J k " and Jk3. A study of gen in the Kidd system, which we suggest this donor's family was not possible. should be called Jk:3 in accordance with reOur studies with anti-Jk3 have provided cent nomenclature in other blood g r o u p ~ . ' * ~further evidence of complexity within the Reactivity of this primary antigen appears to Kidd blood group system, in demonstrating be unaffected when the controlling gene is that variation in expression on red blood cells present in the heterozygous state, but it is of the J k 3 gene on one hand, and the J k " and undetectable on the red blood cells of an indi- J k bgenes on the other, are not necessarily in vidual who is homozygous for a silent allele at harmony. this locus. The reduced expression of J k 3 detected on J. D.'s red blood cells, on the other References hand, appears to be affecting the normal exI . Allen, F. H., Jr., and R. E. Rosenfield: Notation pression of the J k a gene. It is possible that for the Kell blood-group system. Transfusion 1:305, 1961. she may have inherited only a single Jk" gene,
244 2.
3.
4.
5.
6. 7.
8.
HUMPHREY A N D MOREL Arcara, P. C., M. A. O’Connor, and R. M. Dimmette: A family with three Jk(a-b-) members. Transfusion 9:282, 1969. Crawford, M. N., T. J. Greenwalt, T. Sasaki, P. Tippett, R. Sanger, and R . R. Race: T h e phenotype Lu(a-b-) together with unconventional Kidd groups in one family. Transfusion 1:228, 1961. Day, D., H. A. Perkins, and B. Sams: The minusminus phenotype in the Kidd system. Transfusion5:315, 1965. Marsh, W. L., R. @yen, and M. E. Nichols: Kidd blood-group antigens of leukocytes and platelets. Transfusion 14:378, 1974. -: Scoring of hemagglutination reactions. Transfusion 12:352, 1972. Pinkerton, F. J., L. E. Mermod, B. A. Liles, J . A. Jack, and J. Noades: The phenotype Jk(a-b-) in the Kidd blood group system. Vox Sang. 4:155, 1959. Race, R. R., and R. Sanger: Blood Groups in Man, 5th ed. Oxford, Blackwell Scientific, 1968.
Transfusion May-June 1976
Rosenfield, R. E., F. H. Allen, Jr., S. N . Swisher, and S. Kochwa: A review of Rh serology and presentation of a new terminology. Transfusion 2:287, 1962. 10. Silver, R. T., J. M . Haber, and A. Kellner: Evidence for a new allele in the Kidd blood group system in indians of Northern Mato Grosso, Brazil. Nature 186:481, 1960. I I . Yokoyama, M., L. E. Mermod, and A. Stegmaier: Further examples of Jk(a-b-) blood in Hawaii. Vox Sang. 12:154, 1967. 9.
Arvilla J. Humphrey, B.S., MT(ASCP)SBB, Assistant Supervisor, General Laboratory, Irwin Memorial Blood Bank of the San Francisco Medical Society, 270 Masonic Avenue, San Francisco, California 941 18. Phyllis A. Morel, B.A., MT(ASCP)SBB, Supervisor, Reference Laboratory, Irwin Memorial Blood Bank of the San Francisco Medical Society, 270 Masonic Avenue, San Francisco, California 941 15. (Reprint requests).
First International Symposium on HLA and Disease An important international meeting will be held in Paris, France from June 23-25, 1976 on the topical subject of the relationship between HLA and Disease. During this first symposium on this subject, invited speakers will lecture on the basic principles (D. Shreffler, J . Klein, R. Payne, J . J . Van Rood, R. Ceppellini, C. A. Clarke), results already obtained ( A . Svejgaard, P. I. Terasaki), clinical implications (J. Dausset) and fundamental hypotheses explaining the associations ( R . Zinkernagel, W. F. Bodmer, D. B. Amos). Workshop sessions will bring together biologists and clinicians of every specialty: rheumatology (D. A . Brewerton, F. Delbarre), neurology (T. Fog, F. Lehermitte), dermatology (E. M . Farber, J. Civatte, J . Thivolet), endocrinology (J. Nerup, G. Cathelineau), gastroenterology (W. Strober, I. R. Mackay, J . P. Benhamou, J . Rey), allergy (A. d e Weck, M . N. Blumenthal) immunopathology (H. Kunkel, M . Seligmann), malignant diseases ( M . J . Simons, J. L. Amiel), other diseases (P. J . Morris, P. Royer). A special session will be devoted to a discussion of the possible mechanisms of associations between HLA and disease (H. 0. McDevitt, F. Jacob). For any information, please write to: Congres Services, I rue jules Lefebvre, 75009 Paris, France.
