- Email: [email protected]
BORN TO DRINK?
216 ELISA and R.I.A. The possible activation of R.F. during pregnancy deserves further investigation.
obtained by the
Rubella Department, Statens Seruminstitut, DK 2300 Copenhagen S, Denmark
MOGENS
VEJTORP
We agree with Levinsky et al. that clarification of the problems is very important and we look forward to the second phase of their investigation.7
Department of Obstetrics and Gynecology, Mount Sinai School of Medicine, New York, N.Y. 10029, U.S.A.
IMMUNE COMPLEXES IN PREGNANCY
SIR,-Dr Levinsky and colleagues’ disagree with our statement2 that immune complexes do not seem to be a normal feature of pregnancy. They claim that our negative findings with the Raji-cell radioimmunoassay3 provide information about the assay system but do not permit conclusions about the presence or absence of immune complexes in normal and preeclamptic pregnancy. may differ in
We agree that immune complexes antibody class and subclass, size, complement-binding characteristics, and, certainly, antigen. Different immune complexes may well become detectable by a variety of different assays, depending on the quality of the complex.4 This theoretical concept has been confirmed in a collaborative study organised by the immunology unit of the World Health Organisation, in which eighteen methods for the detection of immune complexes were compared in a variety of clinical stiuations.5 On the other hand evidence is still lacking which could confirm that the material reacting positively in the assay developed by Levinsky et al.6 and in many other assays in fact represents immune complexes.4 Even if such proof were provided it would be difficult to understand how non-complement-based immune complexes could play a part in the immunological tolerance of the fetal allograft or the pathogenesis of pre-eclampsia/eclampsia. Studies by Rocklin et al. and in our laboratory8 indicate that an immunoglobulin of the IgG class and not immune complexes may be important for the preservation of pregnancy. The W.H.O. study5 and Schur’s review4 show that many problems related to assays for the detection of immune complexes remain to be resolved. We feel strongly that, until more specific techniques for the detection of immune complexes become available, positive results necessitate a greater degree of scepticism than negative ones. In view of Levinsky’s claim’ that Fc-determined assays may detect different immune complexes than complement-determined assays do it was surprising to see a very satisfactory correlation between his Fc-determined assay results and those obtained in the same patients with a complement-based assay (Clq).9 The absence of immune complexes in normal as well as pre-eclamptic pregnancies, as judged by complement-based immune-complex assay, was reported by us2 and by Knox et al.lo Knox et al. used the Raji-cell radioimmunoassay, as we did, as well as Clq-binding, the technique utilised by Levinsky et al. Further investigations are certainly needed to clarify the
divergence same
in results obtained
by
different groups
using
the
techniques.
We still believe that no conclusions can be drawn about the presence of immune complexes in normal and pre-eclamptic/ eclamptic pregnancy. We have suggested2that this conclusion does not preclude an immunological aetiology for the syndrome of toxasmia of pregnancy, nor does it contradict the possibility of an immunological mechanism in the preservation of the fetal alograft. Our conception of such a mechanism will be published elsewhere. II 1.
2. 3.
J., Stirrat, G. M., Redman, C. W. G. Lancet, 1978, ii, 1210. Gleicher, N., Theofilopoulos, A. N., Beers, P. ibid. p. 1108. Theofilopoulos, A. N., Wilson, C. B., Dixon, F. J. J. clin. Invest. 1976, 57,
Levinsky,
R.
169. 4. Schur, P. H. New Engl. Med. 1978, 298, 161. 5. Lambert, P. H., and others. J. clin. Lab. Immun. 1978, 1,1. 6. Levinsky, R. J., Soothill, J. F. Clin. exp. Immun. 1977, 29, 428. 7. Rocklin, R. E., and others. New Eng. J. Med. 1976, 295, 1209. 8. Gleicher, N., and others. Am. J. Obstet. Gynec. (in the press). 9. Stirrat, G. M., Redman, C. W. G., Levinsky, R. J. Br. med J. 1978, 10. Knox, G E, and others Am. J. Obstet. Gynec. 1978, 152, 87. 11. Gleicher, N., Deppe, G., Cohen, C. J. Obstet. Gynec. (in the press).
1, 1450.
NORBERT GLEICHER
Department of Immunopathology, Scripps Clinic and Research Foundatior La Jolla, California ARGYRIOS N. THEOFILOPOULOS
BORN TO DRINK?
SIR Your editorial (Jan. 6, p. 24) ends: "One preventive strategy which merits further investigation is the detection of individuals at particular risk of becoming dependent on alcohol because of some genetic predisposition". Let us suppose that, at vast trouble and expense, all these individuals throughout the country are identified. What do we then do? Presumably, everyone would be solemnly warned that he had a genetic predisposition to becoming dependent on alcohol, and he should therefore be restrained in his drinking or, preferably, not drink at all. If, Sir, you believe that this would lessen the number of alcoholics, you will believe anything. 5, The Close, Tilford Road,
JOHN W. TODD
Farnham, Surrey
.Dr Todd
assumes
that
we were
advocating immediate whole-
population screening for predisposition to alcoholism and rightly suggests that this would be futile. We were advocating research directed towards finding possible genetic markers; if any were found, they would more appropriately be used among high-risk groups, such as brewery workers or children of alcoholics-ED. L.
INHERITANCE OF TUBEROUS SCLEROSIS
SIR The 1978 report’ of tuberous sclerosis in two sibs whose parents were normal prompts us to report a similar observation. In our family there were four girls and one boy. The first and fourth born (both girls) had unequivocal tuberous sclerosis. The parents were examined several times and skull X-rays were done. Neither showed any clinical symptoms or signs of tuberous sclerosis. Computerised tomography were not available at the time and air encephalograms seemed unjustified. At the time of the first child’s birth the parental ages were 23 and 21 years. There was no consanguinity and there was no history of any other person in the pedigree having any signs or symptoms suggestive of tuberous sclerosis. The manifestations, particularly those of the skin, may be very variable.2 Thus non-penetrance is possible, though it seems unlikely. An autosomal recessive form or gonadal mosaicism in one of the normal parents are other possible explanations. Mosaicism was postulated by BowenJ when two normal parents had two children with classic achondroplasia. In our family one of the children with tuberous sclerosis also had congential adrenal hyperlasia as did the third (girl) and fifth (boy) born children. The second child was the only one without either defect. Supported in part by the Medical Research Council of Canada grant MA-4539 and the Alberta Children’s Research Centre. Departments of Medical Genetics and Pediatrics, University of British Columbia, and Alberta Children’s Hospital Research Centre, Calgary, Canada 1 Wilson, J., Carter, C. O. Lancet, 1978, ii, 340. 2. Kreyenberg, G., Delbranco, E., Haack, K. Z. Psychiat. 3. Bowen, P. Birth Defects orig. Art. Ser. 1974, 10, 31.
R. B. LOWRY H. G. DUNN
R. P. PARIS
1930, 128, 236.
obtained by the
Rubella Department, Statens Seruminstitut, DK 2300 Copenhagen S, Denmark
MOGENS
VEJTORP
We agree with Levinsky et al. that clarification of the problems is very important and we look forward to the second phase of their investigation.7
Department of Obstetrics and Gynecology, Mount Sinai School of Medicine, New York, N.Y. 10029, U.S.A.
IMMUNE COMPLEXES IN PREGNANCY
SIR,-Dr Levinsky and colleagues’ disagree with our statement2 that immune complexes do not seem to be a normal feature of pregnancy. They claim that our negative findings with the Raji-cell radioimmunoassay3 provide information about the assay system but do not permit conclusions about the presence or absence of immune complexes in normal and preeclamptic pregnancy. may differ in
We agree that immune complexes antibody class and subclass, size, complement-binding characteristics, and, certainly, antigen. Different immune complexes may well become detectable by a variety of different assays, depending on the quality of the complex.4 This theoretical concept has been confirmed in a collaborative study organised by the immunology unit of the World Health Organisation, in which eighteen methods for the detection of immune complexes were compared in a variety of clinical stiuations.5 On the other hand evidence is still lacking which could confirm that the material reacting positively in the assay developed by Levinsky et al.6 and in many other assays in fact represents immune complexes.4 Even if such proof were provided it would be difficult to understand how non-complement-based immune complexes could play a part in the immunological tolerance of the fetal allograft or the pathogenesis of pre-eclampsia/eclampsia. Studies by Rocklin et al. and in our laboratory8 indicate that an immunoglobulin of the IgG class and not immune complexes may be important for the preservation of pregnancy. The W.H.O. study5 and Schur’s review4 show that many problems related to assays for the detection of immune complexes remain to be resolved. We feel strongly that, until more specific techniques for the detection of immune complexes become available, positive results necessitate a greater degree of scepticism than negative ones. In view of Levinsky’s claim’ that Fc-determined assays may detect different immune complexes than complement-determined assays do it was surprising to see a very satisfactory correlation between his Fc-determined assay results and those obtained in the same patients with a complement-based assay (Clq).9 The absence of immune complexes in normal as well as pre-eclamptic pregnancies, as judged by complement-based immune-complex assay, was reported by us2 and by Knox et al.lo Knox et al. used the Raji-cell radioimmunoassay, as we did, as well as Clq-binding, the technique utilised by Levinsky et al. Further investigations are certainly needed to clarify the
divergence same
in results obtained
by
different groups
using
the
techniques.
We still believe that no conclusions can be drawn about the presence of immune complexes in normal and pre-eclamptic/ eclamptic pregnancy. We have suggested2that this conclusion does not preclude an immunological aetiology for the syndrome of toxasmia of pregnancy, nor does it contradict the possibility of an immunological mechanism in the preservation of the fetal alograft. Our conception of such a mechanism will be published elsewhere. II 1.
2. 3.
J., Stirrat, G. M., Redman, C. W. G. Lancet, 1978, ii, 1210. Gleicher, N., Theofilopoulos, A. N., Beers, P. ibid. p. 1108. Theofilopoulos, A. N., Wilson, C. B., Dixon, F. J. J. clin. Invest. 1976, 57,
Levinsky,
R.
169. 4. Schur, P. H. New Engl. Med. 1978, 298, 161. 5. Lambert, P. H., and others. J. clin. Lab. Immun. 1978, 1,1. 6. Levinsky, R. J., Soothill, J. F. Clin. exp. Immun. 1977, 29, 428. 7. Rocklin, R. E., and others. New Eng. J. Med. 1976, 295, 1209. 8. Gleicher, N., and others. Am. J. Obstet. Gynec. (in the press). 9. Stirrat, G. M., Redman, C. W. G., Levinsky, R. J. Br. med J. 1978, 10. Knox, G E, and others Am. J. Obstet. Gynec. 1978, 152, 87. 11. Gleicher, N., Deppe, G., Cohen, C. J. Obstet. Gynec. (in the press).
1, 1450.
NORBERT GLEICHER
Department of Immunopathology, Scripps Clinic and Research Foundatior La Jolla, California ARGYRIOS N. THEOFILOPOULOS
BORN TO DRINK?
SIR Your editorial (Jan. 6, p. 24) ends: "One preventive strategy which merits further investigation is the detection of individuals at particular risk of becoming dependent on alcohol because of some genetic predisposition". Let us suppose that, at vast trouble and expense, all these individuals throughout the country are identified. What do we then do? Presumably, everyone would be solemnly warned that he had a genetic predisposition to becoming dependent on alcohol, and he should therefore be restrained in his drinking or, preferably, not drink at all. If, Sir, you believe that this would lessen the number of alcoholics, you will believe anything. 5, The Close, Tilford Road,
JOHN W. TODD
Farnham, Surrey
.Dr Todd
assumes
that
we were
advocating immediate whole-
population screening for predisposition to alcoholism and rightly suggests that this would be futile. We were advocating research directed towards finding possible genetic markers; if any were found, they would more appropriately be used among high-risk groups, such as brewery workers or children of alcoholics-ED. L.
INHERITANCE OF TUBEROUS SCLEROSIS
SIR The 1978 report’ of tuberous sclerosis in two sibs whose parents were normal prompts us to report a similar observation. In our family there were four girls and one boy. The first and fourth born (both girls) had unequivocal tuberous sclerosis. The parents were examined several times and skull X-rays were done. Neither showed any clinical symptoms or signs of tuberous sclerosis. Computerised tomography were not available at the time and air encephalograms seemed unjustified. At the time of the first child’s birth the parental ages were 23 and 21 years. There was no consanguinity and there was no history of any other person in the pedigree having any signs or symptoms suggestive of tuberous sclerosis. The manifestations, particularly those of the skin, may be very variable.2 Thus non-penetrance is possible, though it seems unlikely. An autosomal recessive form or gonadal mosaicism in one of the normal parents are other possible explanations. Mosaicism was postulated by BowenJ when two normal parents had two children with classic achondroplasia. In our family one of the children with tuberous sclerosis also had congential adrenal hyperlasia as did the third (girl) and fifth (boy) born children. The second child was the only one without either defect. Supported in part by the Medical Research Council of Canada grant MA-4539 and the Alberta Children’s Research Centre. Departments of Medical Genetics and Pediatrics, University of British Columbia, and Alberta Children’s Hospital Research Centre, Calgary, Canada 1 Wilson, J., Carter, C. O. Lancet, 1978, ii, 340. 2. Kreyenberg, G., Delbranco, E., Haack, K. Z. Psychiat. 3. Bowen, P. Birth Defects orig. Art. Ser. 1974, 10, 31.
R. B. LOWRY H. G. DUNN
R. P. PARIS
1930, 128, 236.