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IgE IN ATAXIA-TELANGIECTASIA AND FAMILY MEMBERS
1089 others are concluded, (b) he is of sound mind, and (c) he is under no external constraint. S. L. HENDERSON SMITH.
importance of IgE in the immunological defence mechanisms awaits further clarification. We thank Dr. E. Boder and Dr. W. B. Reed for permission to study their patients. The genetic markers (Gm and Inv) were detected by Dr. A. G. Steinberg of the Case Western Reserve University, Cleveland, Ohio.
FAMILY MEMBERS SiR,-The first passive transfer of reaginic antibody was achieved in 1921 when Prausnitz injected Kustner’s serum into his own skin and on subsequent challenge with the allergin observed a wheal-and-flare response.’i Over 40
IgE IN ATAXIA-TELANGIECTASIA AND
passed until the Ishizakas, using serum from allergic individuals, were able to isolate and begin the physiological and biochemical analysis of this reaginic protein they called immunoglobulin E (IgE).2 As we would predict with a new immunoglobulin class, 2 patients (N. D. and P. S.) 3,44 were discovered to have an IgE-type myeloma. Since then, many accounts of its physicochemical properties, structure, physiological activities,2 development during childhood,5
DOUGLAS BIGGAR NORMAND LAPOINTE KIMISHIGE ISHIZAKA HILAIRE MEUWISSEN ROBERT A. GOOD DOMINIQUE FROMMEL.
Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota, and Good Samaritan
Hospital; Baltimore, Maryland.
years
and possible function in the immune defence mechanisms have been published.6-9
PHENOBARBITONE IN RHESUS HÆMOLYTIC DISEASE
SiR,—The conclusion by Dr. McMullin and his colleagues (Nov. 7, p. 949) that it is probably unjustifiable to withhold phenobarbitone treatment from babies with rhesus haemolytic disease
be allowed
cannot
to
pass without comment.
First, it is important to know whether the linctus used contained alcohol, since this too is known to stimulate the bilirubin-conjugation enzyme system. Second, the method of selecting cases either for phenobarbitone or as controls, although giving an equal distribution, is not entirely
satisfactory since it must have been possible for the doctor deciding subsequent treatment, and possibly the technician carrying a "
out
bilirubin estimations,
In
series from this
laboratory,6 using the reversedescribed by Ishizaka and Ishizaka,lo 11 out of 16 ataxia-telangiectasia patients were found to be deficient in IgE. Using a double antibody technique and anti-P.S. antiserum, we have found all 15 patients and 65% of family members to be deficient in serum-IgE (see figure). No correlation could be made between the serum-IgE and the clinical histories, physical examinations, allergic manifestations, serum-immunoglobulins G, A, and M, genetic markers Gm and Inv, and the other biological analyses undertaken. The abnormality we have observed in ataxia-telangiectasia patients and their family members could reflect a genetic association of this disease with a gene required for the synthesis of normal IgE or IgE subclasses. The biological a
cutaneous-anaphylaxis
test
1. 2. 3. 4.
Prausnitz, C., Küstner, J. Ventral Bakt. 1921, 86, 160. Ishizaka, K., Ishizaka, T. J. Allergy, 1968, 42, 330. Johansson, S. G. O., Bennich, H. Immunology, 1967, 13, 381. Ogawa, M., Kochwa, S., Smith, C., Ishizaka, K., McIntyre, O. R. New Engl. J. Med. 1969, 281, 1217. 5. Berg, T., Johansson, S. G. O. Acta paediat. Scand. 1969, 58, 513. 6. Ammann, A. J., Cain, W. A., Ishizaka, K., Hong, R., Good, R. A. New Engl. J. Med. 1969, 281, 469. 7. Cain, W. A., Ammann, A. J., Hong, R., Ishizaka, K., Good, R. A. J. clin. Invest. 1969, 48, 12A. 8. Polmar, S. H., Lischner, H. W., Huang, N., Waldman, T. A.,
Terry, W. D. Am. Fedn clin. Res. 1970, 18, 431 (abstr.). 9. Ammann, A. J., Hong, R., Good, R. A. New Engl. J. Med. 1970, 283, 542. 10. Ishizaka, K., Ishizaka, T. J. Immun. 1968, 100, 554.
know whether
or not
cord hsemoglobin and bilirubin levels, nor at this stage could phenobarbitone have affected the condition of the infant. But the indication for " late " or repeated exchange transfusion, a capillary-blood serum-bilirubin above 20 mg. per 100 ml." cannot be applied precisely. The timing of blood-samples is largely determined by clinical observations and convenience, while the technical error at 20 mg. per 100 ml. is of the order of ±2 mg. per 100 ml.; Dr. McMullin and his colleagues apparently accept this when stating that their aim was to avoid values above 22 mg. per 100 ml. The actual decision to perform exchange transfusion is often anticipatory and influenced by the infant’s age, stage of gestation, clinical condition, the overall severity of hxmolytic disease, possibly sex, or even the mother’s past obstetric history. There is thus a element the decision, and subgoverning large subjective conscious bias could easily occur if it were possible to know whether a patient was a treated case or control. In table 11 we find that the significant findings are in relation only to the less severely affected infants who did not meet the cord-blood criteria for " early " exchange transfusion. I was surprised that as many as 14 such infants (44%) needed " late " exchange transfusion-12 % for the phenobarbitone but 80% for the control cases. I have therefore looked at relevant cases for our own material for two separate years-i.e., Coombs-positive infants with cordhaemoglobin values of 13 g. per 100 ml. or more and cordbilirubin values of 4 mg. per 100 ml. or less. For the years 1965 and 1969, respectively, 49 out of 168 (29%) and 30 out of 118 (25%) such cases received exchange transfusion. Selection for exchange transfusion was usually because of a cord-bilirubin value of 2-8 mg. per 100 ml. or greater, but any infant developing hyperbilirubinxmia was also treated in this way. If anything, we would expect to have overtreated rather than undertreated our patients. Another surprising feature of Dr. McMullin’s cases was that all infants selected for " late " exchange transfusion required only one transfusion, whereas in my experience if exchange transfusion is delayed until "
Serum-IgE in ataxia-telangiectasia patients and family members (IgE-myeloma P.S.).
to
particular baby was receiving phenobarbitone. Such knowledge would not influence selection for early " exchange transfusion because this was based on
importance of IgE in the immunological defence mechanisms awaits further clarification. We thank Dr. E. Boder and Dr. W. B. Reed for permission to study their patients. The genetic markers (Gm and Inv) were detected by Dr. A. G. Steinberg of the Case Western Reserve University, Cleveland, Ohio.
FAMILY MEMBERS SiR,-The first passive transfer of reaginic antibody was achieved in 1921 when Prausnitz injected Kustner’s serum into his own skin and on subsequent challenge with the allergin observed a wheal-and-flare response.’i Over 40
IgE IN ATAXIA-TELANGIECTASIA AND
passed until the Ishizakas, using serum from allergic individuals, were able to isolate and begin the physiological and biochemical analysis of this reaginic protein they called immunoglobulin E (IgE).2 As we would predict with a new immunoglobulin class, 2 patients (N. D. and P. S.) 3,44 were discovered to have an IgE-type myeloma. Since then, many accounts of its physicochemical properties, structure, physiological activities,2 development during childhood,5
DOUGLAS BIGGAR NORMAND LAPOINTE KIMISHIGE ISHIZAKA HILAIRE MEUWISSEN ROBERT A. GOOD DOMINIQUE FROMMEL.
Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota, and Good Samaritan
Hospital; Baltimore, Maryland.
years
and possible function in the immune defence mechanisms have been published.6-9
PHENOBARBITONE IN RHESUS HÆMOLYTIC DISEASE
SiR,—The conclusion by Dr. McMullin and his colleagues (Nov. 7, p. 949) that it is probably unjustifiable to withhold phenobarbitone treatment from babies with rhesus haemolytic disease
be allowed
cannot
to
pass without comment.
First, it is important to know whether the linctus used contained alcohol, since this too is known to stimulate the bilirubin-conjugation enzyme system. Second, the method of selecting cases either for phenobarbitone or as controls, although giving an equal distribution, is not entirely
satisfactory since it must have been possible for the doctor deciding subsequent treatment, and possibly the technician carrying a "
out
bilirubin estimations,
In
series from this
laboratory,6 using the reversedescribed by Ishizaka and Ishizaka,lo 11 out of 16 ataxia-telangiectasia patients were found to be deficient in IgE. Using a double antibody technique and anti-P.S. antiserum, we have found all 15 patients and 65% of family members to be deficient in serum-IgE (see figure). No correlation could be made between the serum-IgE and the clinical histories, physical examinations, allergic manifestations, serum-immunoglobulins G, A, and M, genetic markers Gm and Inv, and the other biological analyses undertaken. The abnormality we have observed in ataxia-telangiectasia patients and their family members could reflect a genetic association of this disease with a gene required for the synthesis of normal IgE or IgE subclasses. The biological a
cutaneous-anaphylaxis
test
1. 2. 3. 4.
Prausnitz, C., Küstner, J. Ventral Bakt. 1921, 86, 160. Ishizaka, K., Ishizaka, T. J. Allergy, 1968, 42, 330. Johansson, S. G. O., Bennich, H. Immunology, 1967, 13, 381. Ogawa, M., Kochwa, S., Smith, C., Ishizaka, K., McIntyre, O. R. New Engl. J. Med. 1969, 281, 1217. 5. Berg, T., Johansson, S. G. O. Acta paediat. Scand. 1969, 58, 513. 6. Ammann, A. J., Cain, W. A., Ishizaka, K., Hong, R., Good, R. A. New Engl. J. Med. 1969, 281, 469. 7. Cain, W. A., Ammann, A. J., Hong, R., Ishizaka, K., Good, R. A. J. clin. Invest. 1969, 48, 12A. 8. Polmar, S. H., Lischner, H. W., Huang, N., Waldman, T. A.,
Terry, W. D. Am. Fedn clin. Res. 1970, 18, 431 (abstr.). 9. Ammann, A. J., Hong, R., Good, R. A. New Engl. J. Med. 1970, 283, 542. 10. Ishizaka, K., Ishizaka, T. J. Immun. 1968, 100, 554.
know whether
or not
cord hsemoglobin and bilirubin levels, nor at this stage could phenobarbitone have affected the condition of the infant. But the indication for " late " or repeated exchange transfusion, a capillary-blood serum-bilirubin above 20 mg. per 100 ml." cannot be applied precisely. The timing of blood-samples is largely determined by clinical observations and convenience, while the technical error at 20 mg. per 100 ml. is of the order of ±2 mg. per 100 ml.; Dr. McMullin and his colleagues apparently accept this when stating that their aim was to avoid values above 22 mg. per 100 ml. The actual decision to perform exchange transfusion is often anticipatory and influenced by the infant’s age, stage of gestation, clinical condition, the overall severity of hxmolytic disease, possibly sex, or even the mother’s past obstetric history. There is thus a element the decision, and subgoverning large subjective conscious bias could easily occur if it were possible to know whether a patient was a treated case or control. In table 11 we find that the significant findings are in relation only to the less severely affected infants who did not meet the cord-blood criteria for " early " exchange transfusion. I was surprised that as many as 14 such infants (44%) needed " late " exchange transfusion-12 % for the phenobarbitone but 80% for the control cases. I have therefore looked at relevant cases for our own material for two separate years-i.e., Coombs-positive infants with cordhaemoglobin values of 13 g. per 100 ml. or more and cordbilirubin values of 4 mg. per 100 ml. or less. For the years 1965 and 1969, respectively, 49 out of 168 (29%) and 30 out of 118 (25%) such cases received exchange transfusion. Selection for exchange transfusion was usually because of a cord-bilirubin value of 2-8 mg. per 100 ml. or greater, but any infant developing hyperbilirubinxmia was also treated in this way. If anything, we would expect to have overtreated rather than undertreated our patients. Another surprising feature of Dr. McMullin’s cases was that all infants selected for " late " exchange transfusion required only one transfusion, whereas in my experience if exchange transfusion is delayed until "
Serum-IgE in ataxia-telangiectasia patients and family members (IgE-myeloma P.S.).
to
particular baby was receiving phenobarbitone. Such knowledge would not influence selection for early " exchange transfusion because this was based on