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SCREENING BLOOD-DONORS FOR AU ANTIGEN
465
corresponding to that of neuraminidase-treated A.F.P. ThiI variant is probably the extreme case, with totally deficient sialation of the protein. In retrospect, even in starch gels or cellulose acetate at pH 86 the mobilities of the A.F.P. band are different in most cases, and the net apparent mobility is the result of summation of the properties of the A.F.p.s sialated to varying degrees. L. R. PURVES South African Institute for E. VAN DER MERWE Medical Research, I. BERSOHN. Johannesburg. ABSENCE OF &agr;1-FETOPROTEIN ANTIGEN OR ANTIBODY IN MATERNAL SERA SiR,-Dr. Foy and his colleaguesreport the presence of ocl-fetoprotein (A.F.P.) in 7 (35%) of 20 pregnant women and in 7 of 7 newborn babies. Several investigators 2,3 have shown that the concentration of A.F.P. in fetal serum reaches a peak at about 12-20 weeks’ gestation and then falls progressively. Although detectable in up to 100% of cord sera from newborns, depending on the sensitivity of the method, the concentration of A.F.P. at birth is less than 1% of its peak concentration early in fetal life and falls rapidly, becoming undectable after the first few weeks or months of life. Therefore, the detection of A.F.P. in the sera of newborns is not surprising, but the report of A.F.P. in maternal sera, particularly only in women past 30 weeks’ gestation, was unexpected since the concentration in fetal serum is very low and falling at this time. Therefore, 162 samples of sera from normal pregnant women, at all stages of gestation, were tested both for A.F.P. and for antibody to A.F.P. The rabbit antiserum used, prepared by using a partially purified hepatoma serum as immunising agent, after adsorption, was shown to be monospecific, with complete immunological identity to fetal A.F.P. and with comparable sensitivity to antisera used in previous work.4.ó All sera were tested by Ouchterlony immunodiffusion and also by electro-immunodiffusion in agar gel, a technique 40 times more sensitive than the Ouchterlony method. The gestational ages of the women whose
sera
were
ti-qtpci
arP
thrown helnw-
Neither A.F.P. nor antibody to A.F.P. was found in any of the 162 samples from 142 pregnant women, including several tested at weekly intervals throughout gestation. We were therefore unable to confirm the preliminary report by Dr. Foy and his colleagues.l Possibly the preline they noted in maternal sera, described as cipitation " much weaker " than in newborn sera, was a non-immunological precipitate, or it may be that the antiserum used was not totally specific. One wonders whether these workers were detecting a protein other than oci-fetoprotein, such as P-fetoprotein.or cc,-H-globulin .7 These other fetal proteins, unlike A.F.P., appear nonspecifically in a wide variety of diseases and neoplasma, much as does the m2 acutephase protein of rats. 1. 2. 3. 4. 5. 6.
7.
Foy, H., Kondi, A., Parker, A. M., Stanley, R., Venning, C. D. Lancet, 1970, i, 1336. Gitlin, D., Boesman, M. J. clin. Invest. 1966, 45, 1826. Van Furth, R., Adinolfi, M. Nature, 1969, 222, 1296. Alpert, M. E., Uriel, J., de Nechaud, M. New Engl. J. Med. 1968, 278, 948. Alpert, M. E. Clin. Res. 1969, 17, 461. Economopoulos, I., Theodoropoulos, G., Sakellaropoulos, N. Lancet, 1970, i, 1337. Buffe, D., Rimbaut, C., Burtin, P. Int. J. Cancer, 1968, 3, 850.
In any event, despite the use of sensitive methods, neither the hepatoma-specific A.F.P., nor antibody, could be detected in maternal sera. This indicates that A.F.P., despite its small molecular size,’ does not cross the normal human placenta. Massachusetts General and Robert B. Brigham Hospitals,
Department of Medicine, Harvard Medical School, Boston. Boston
for Women, Departments of Obstetrics and Gynecology, Harvard Medical School, Boston, Massachusetts.
ELLIOT ALPERT.
Hospital
JAMES ZUCKERMAN.
&agr;1-FETOPROTEIN IN SPAIN SiR,-We have tested for al-fetoprotein (A.F.P.) in sera from 17 patients with primary carcinoma of the liver and 100 with other liver diseases (cirrhosis, acute viral hepatitis, acute alcoholic hepatitis, haemochromatosis, and hepatic metastases). All these diagnoses were confirmed histologically. A.F.P. was detected by Ouchterlony immunodiffusion on agar gel. The antiserum was prepared by injecting rabbits with pooled A.F.P.-positive sera from patients with hepatocellular carcinoma, and made specific by subsequent adsorption with pooled normal and cirrhotic adult serum. The test was positive in 7 (42%) of 17 patients with primary carcinoma of the liver; 2 of these had associated cryptogenic cirrhosis, 1 had alcoholic cirrhosis, and 4 had no cirrhosis. We have not encountered any false-positives. In 4 out of the 7 positive cases we were only able to obtain
line of precipitation after filling the peripheral well two or three times. This suggests that more sensitive immunological techniques will give a higher incidence of positive results. We thank Prof. J. Uriel and Dr. B. de Nechaud for providing a
the first
sample of antiserum.
Liver Unit, Hospital Clínico y Provincial, University of Barcelona. Department of Investigation, Hospital N.S. del Mar, Barcelona, Spain.
J. TERES A. BERTRAN A. MAS.
J. GRAS.
SCREENING BLOOD-DONORS FOR AU ANTIGEN the conclusions of Dr. Alter and his with SiR,-We agree We have detected Au/s.H. 18, 142). (July p. colleagues antigen in 8 out of 800 apparently healthy paid blood-donors (1%) and in 1 of 250 unpaid blood-donors (0-4%). The recipient of a unit of blood from an Au-positive donor developed hepatitis 28 days later despite injection of 8 g. of y-globulin the day after the transfusion. It is noteworthy that in 900 patients in the hospital with no known liver disease the antigen was detected in only 3 (0-3%). Liver biopsy in one of these patients, who had normal liverfunction tests, showed persistent hepatitis. We think these observations show the need for systematic testing for Au antigen in blood-banks. This is especially so in relation to blood from professional donors, since in our series antigensmia was three times commoner among these than in the hospital population. In Spain, anti-Au serum with confirmed specificityis especially common in patients with alcoholic cirrhosis (20%), so there are no difficulties with serum supply. Departments of Internal Medicine and Hæmatology, General Hospital, Ciudad Sanitaria de la
Seguridad Social, Barcelona, Spain.
8. 9.
J. GUARDIA R. BACARDÍ J. M. HERNÁNDEZ-S. J. M. MARTÍNIZ-V.
Cossart, Y. E. Personal communication. Guardia, J. Doctoral thesis, University of Barcelona, 1970.
corresponding to that of neuraminidase-treated A.F.P. ThiI variant is probably the extreme case, with totally deficient sialation of the protein. In retrospect, even in starch gels or cellulose acetate at pH 86 the mobilities of the A.F.P. band are different in most cases, and the net apparent mobility is the result of summation of the properties of the A.F.p.s sialated to varying degrees. L. R. PURVES South African Institute for E. VAN DER MERWE Medical Research, I. BERSOHN. Johannesburg. ABSENCE OF &agr;1-FETOPROTEIN ANTIGEN OR ANTIBODY IN MATERNAL SERA SiR,-Dr. Foy and his colleaguesreport the presence of ocl-fetoprotein (A.F.P.) in 7 (35%) of 20 pregnant women and in 7 of 7 newborn babies. Several investigators 2,3 have shown that the concentration of A.F.P. in fetal serum reaches a peak at about 12-20 weeks’ gestation and then falls progressively. Although detectable in up to 100% of cord sera from newborns, depending on the sensitivity of the method, the concentration of A.F.P. at birth is less than 1% of its peak concentration early in fetal life and falls rapidly, becoming undectable after the first few weeks or months of life. Therefore, the detection of A.F.P. in the sera of newborns is not surprising, but the report of A.F.P. in maternal sera, particularly only in women past 30 weeks’ gestation, was unexpected since the concentration in fetal serum is very low and falling at this time. Therefore, 162 samples of sera from normal pregnant women, at all stages of gestation, were tested both for A.F.P. and for antibody to A.F.P. The rabbit antiserum used, prepared by using a partially purified hepatoma serum as immunising agent, after adsorption, was shown to be monospecific, with complete immunological identity to fetal A.F.P. and with comparable sensitivity to antisera used in previous work.4.ó All sera were tested by Ouchterlony immunodiffusion and also by electro-immunodiffusion in agar gel, a technique 40 times more sensitive than the Ouchterlony method. The gestational ages of the women whose
sera
were
ti-qtpci
arP
thrown helnw-
Neither A.F.P. nor antibody to A.F.P. was found in any of the 162 samples from 142 pregnant women, including several tested at weekly intervals throughout gestation. We were therefore unable to confirm the preliminary report by Dr. Foy and his colleagues.l Possibly the preline they noted in maternal sera, described as cipitation " much weaker " than in newborn sera, was a non-immunological precipitate, or it may be that the antiserum used was not totally specific. One wonders whether these workers were detecting a protein other than oci-fetoprotein, such as P-fetoprotein.or cc,-H-globulin .7 These other fetal proteins, unlike A.F.P., appear nonspecifically in a wide variety of diseases and neoplasma, much as does the m2 acutephase protein of rats. 1. 2. 3. 4. 5. 6.
7.
Foy, H., Kondi, A., Parker, A. M., Stanley, R., Venning, C. D. Lancet, 1970, i, 1336. Gitlin, D., Boesman, M. J. clin. Invest. 1966, 45, 1826. Van Furth, R., Adinolfi, M. Nature, 1969, 222, 1296. Alpert, M. E., Uriel, J., de Nechaud, M. New Engl. J. Med. 1968, 278, 948. Alpert, M. E. Clin. Res. 1969, 17, 461. Economopoulos, I., Theodoropoulos, G., Sakellaropoulos, N. Lancet, 1970, i, 1337. Buffe, D., Rimbaut, C., Burtin, P. Int. J. Cancer, 1968, 3, 850.
In any event, despite the use of sensitive methods, neither the hepatoma-specific A.F.P., nor antibody, could be detected in maternal sera. This indicates that A.F.P., despite its small molecular size,’ does not cross the normal human placenta. Massachusetts General and Robert B. Brigham Hospitals,
Department of Medicine, Harvard Medical School, Boston. Boston
for Women, Departments of Obstetrics and Gynecology, Harvard Medical School, Boston, Massachusetts.
ELLIOT ALPERT.
Hospital
JAMES ZUCKERMAN.
&agr;1-FETOPROTEIN IN SPAIN SiR,-We have tested for al-fetoprotein (A.F.P.) in sera from 17 patients with primary carcinoma of the liver and 100 with other liver diseases (cirrhosis, acute viral hepatitis, acute alcoholic hepatitis, haemochromatosis, and hepatic metastases). All these diagnoses were confirmed histologically. A.F.P. was detected by Ouchterlony immunodiffusion on agar gel. The antiserum was prepared by injecting rabbits with pooled A.F.P.-positive sera from patients with hepatocellular carcinoma, and made specific by subsequent adsorption with pooled normal and cirrhotic adult serum. The test was positive in 7 (42%) of 17 patients with primary carcinoma of the liver; 2 of these had associated cryptogenic cirrhosis, 1 had alcoholic cirrhosis, and 4 had no cirrhosis. We have not encountered any false-positives. In 4 out of the 7 positive cases we were only able to obtain
line of precipitation after filling the peripheral well two or three times. This suggests that more sensitive immunological techniques will give a higher incidence of positive results. We thank Prof. J. Uriel and Dr. B. de Nechaud for providing a
the first
sample of antiserum.
Liver Unit, Hospital Clínico y Provincial, University of Barcelona. Department of Investigation, Hospital N.S. del Mar, Barcelona, Spain.
J. TERES A. BERTRAN A. MAS.
J. GRAS.
SCREENING BLOOD-DONORS FOR AU ANTIGEN the conclusions of Dr. Alter and his with SiR,-We agree We have detected Au/s.H. 18, 142). (July p. colleagues antigen in 8 out of 800 apparently healthy paid blood-donors (1%) and in 1 of 250 unpaid blood-donors (0-4%). The recipient of a unit of blood from an Au-positive donor developed hepatitis 28 days later despite injection of 8 g. of y-globulin the day after the transfusion. It is noteworthy that in 900 patients in the hospital with no known liver disease the antigen was detected in only 3 (0-3%). Liver biopsy in one of these patients, who had normal liverfunction tests, showed persistent hepatitis. We think these observations show the need for systematic testing for Au antigen in blood-banks. This is especially so in relation to blood from professional donors, since in our series antigensmia was three times commoner among these than in the hospital population. In Spain, anti-Au serum with confirmed specificityis especially common in patients with alcoholic cirrhosis (20%), so there are no difficulties with serum supply. Departments of Internal Medicine and Hæmatology, General Hospital, Ciudad Sanitaria de la
Seguridad Social, Barcelona, Spain.
8. 9.
J. GUARDIA R. BACARDÍ J. M. HERNÁNDEZ-S. J. M. MARTÍNIZ-V.
Cossart, Y. E. Personal communication. Guardia, J. Doctoral thesis, University of Barcelona, 1970.