HLA AND SUDDEN INFANT DEATH

1178 HLA ANTIGEN

reconsideration of the view that epidural analgesia should be allowed if the obstetrician is confident that the patient can labour. to

FREQUENCIES

IN PARENTS OF COT-DEATH INFANTS

-

West Kent General

Hospital,

D.

J. PEARCE P. RAVI

Maidstone, Kent ME14 1ER

INFARCTION OF FALLOPIAN TUBE AFTER TUBAL DIATHERMY

SIR,-We wish to record a complication of laparoscopic sterilisation which we have not seen reported previously. The patient, a 38-year-old para 2+0 had laparoscopic sterilisation performed, diathermy being applied at three separate places on each tube. The pelvic organs were normal, and the appendix had been removed previously. 20 h after the procedure, the patient complained of severe lower abdominal pain. The abdomen was rigid, and there was generalised rebound tenderness, greatest in the lower abdomen. Bowel sounds were present. Excitation tenderness was noted on pelvic examination. Pulse, blood-pressure, and temperature were normal. Laparotomy was performed through a right lower paramedian incision. The small and large bowel were normal throughout their lengths. The fimbriated end of the right fallopian tube was black and infarcted distal to the diathermied areas. There was no evidence of torsion, and both ovaries were healthy. The infundibulopelvic ligaments were normal and the fimbriated end of the left tube was healthy distal to the points of diathermy. Bilateral partial salpingectomy was performed to prevent a similar occurrence in the opposite tube. Postoperatively, signs of paralytic ileus developed but resolved within 48 h with nasogastric suction and intravenous fluids. Histology confirmed that the tube was haemorrhagic and infarcted at the fimbriated end. No other abnormality was noted. The patient was discharged home on the ninth post-

operative day.

Departments of Gynæcology and Surgery, Western Infirmary, Glasgow G11 6NT

W. CORDINER M. J. CARTY C. MACKAY

J.

HLA AND SUDDEN INFANT DEATH

SIR,-It has been suggested that the sudden-infant-death syndrome (S.LD.S.) results from an allergic reaction,’ and that Dermatophagoidespteronyssinus (house-dust mite), &bgr;-lactoglobulin from cow’s milk, and Aspergillus fumigatus are three possible offending antigens.2 Since genes controlling IgE antibody responses may be linked to genes controlling HLA antigens,3we have measured the frequency of HLA antigens in parents of children dying from S.LD.S. (cot deaths). Cases of S.LD.S. were diagnosed by one of us (A.L.W.) on the basis of sudden unexpected infant death with no cause revealed during an extensive post-mortem examination. HLA phenotypes of 66 parents (33 cot-death cases) were determined by a standard lymphocytotoxicity test and a comprehensive panel of HLA antisera. The control group of 375 subjects of both sexes and similar racial origin comprised blood-donors and randomly selected healthy volunteers. HLA antigen frequencies for test and control groups (table) indicate that, although the frequencies of B locus antigens in the s.l.D.s. parents

are

similar

to

those in the control group,

significant heterogeneity for A locus antigens (t= 30-19, p<0.02) with an increase of A10 and possibly W19 in

there is

the parents. 1.

Parish, W. E., Barrett, A. M., Coombs, R. R. A., Gunther, M., Camps, F. E. Lancet, 1960, n, 1106. 2. Turner, K. J., Baldo, B. A., Hilton, J. M. N. Br. med. J 1975, i, 357. 3. Levine, B. B., Stemba, R. H., Fotino, M. Science, 1972, 178, 1201. 4. Marsh, D. G., Bias, W. B., Hsu, S. H., Goodfriend, L. ibid. 1973, 179, 691. 5. Terasaki, P. I., Vredevoe, D. L., Mickey, M. R. Transplantation, 1967, 5, 1057.

’Significant deviation from control antigen frequency. ’(’Significant difference in antigen frequency between paternal

and maternal groups for each antigen and heterogeneity Z’16 over all A locus antigens were calculated by FIsher’s method with a correction for continuity due to Lancaster,’ randomisation testing by computer simulation confirmed the accuracy of this method.

Significant heterogeneity was also observed when fathers were compared separately with controls (;zt6=

and mothers

for fathers; and 32.4, r<001 for 36.7, p<0-003 also and when and maternal were mothers) paternal groups with each other (=34-6, p
compared was

more

bility system.34

The differences in HLA frequencies between mothers and fathers suggest an asymmetry in the role of parental genotypes in s.l.D.s. This could be related to the passive transfer of maternal IgG and/or IgA to the infant during gestation6 and lactation.’ We suggest that the parental contribution to s.l.D.s. is mediated by two effects. Firstly, genes linked to the major histocompatibility system and inherited from both parents could determine an atopic predisposition to the production of specific IgE by the infant. Secondly, maternal genes linked to the major histocompatibility system could have a separate effect via the production of maternal antibody (possibly of IgA class) which is passively transmitted to the offspring dunng 6

Gitlin, taro

D. in Immunology in Obstetrics and Gynecology (edited and N. Carretti). Amsterdam, 1974.

7. Gunther, M. Lancet, 1975, i, 441, 8. Lancaster, H. O Biometrika, 1949,

36, 370.

by

A Cen-

1179 pregnancy and lactation. A genetic predisposition to low levels of certain antibodies in the mother would be reflected by low levels in the fetus and neonate, thus weakening the first line of immunological defence to infection or hypersensitivity in the infant respiratory tract. This notion is supported by the increased frequency of S.LD.S. in bottle-fed babies and by the peak incidence ofs.LD.s. at 3-6 months ofage.7

analysis of the expression of other cell-surface antigens, including possible immune-associated antigens. In addition we intend to correlate these observations with the reported low levels of circulating E and EAC rosette-forming cells in mycosis fungoides, and with the7 finding of a subgroup of patients with raised levels of IgE.b6 University Department Western Infirmary, Glasgow

Tissue Typing Laboratory, Royal Melbourne Hospital, and Department of Surgery, University of Melbourne, Victoria 3050, Australia

RONA MACKIE

University Department of Bacteriology, Royal Infirmary, Glasgow

B. D. TAIT

Pathology Department, Royal Childrens’ Hospital,

University Department A. L. WILLIAMS

Melbourne

of Dermatology,

Department of Medicine,

University of Melbourne

J.

Hæmatology Department, Royal Melbourne Hospital

D. C. COWLING

Immunology, Western Infirmary, Glasgow

HEATHER M. DICK

of Bacteriology and

MARIA B.

DE

SOUSA

D. MATHEWS

A PROFESSOR EMIGRATES

HLA AND MYCOSIS FUNGOIDES

SIR,-My chief mentor, the late Sir James Learmonth, used say that to prolong a correspondence in the columns of even such a journal as The Lancet did harm rather than good. However, Professor Brumfitt and his colleagues (May 15, p. 1072) make such a cogent case and throw out such a direct challenge that I can easily rationalise away any reluctance and reply. In doing so, and in case I am regarded as indulging in special pleading, may I say that I share their financial state both professionally and personally; particularly in regard to the second, I am still at the same lowly merit level as they are, having

to

SIR,-We have determined the HLA antigens of 15 patients with histologically proven mycosis fungoides. This condition is considered to be a slowly evolving T-cell neoplasm’ with mainly cutaneous involvement. Our patients were in the early stage of the disease with lesions of the plaque variety. There were 7 males and 8 females, with a mean age of 56 years. Tissue typing was done by microcytotoxicity on peripheralblood lymphocytes, using a panel of 92 antisera and a modification of the method of Kissmeyer-Nielsen and Kjerbye.2 3 The following HLA antigens were sought: of the A series, 1, 2, 3, 9,10,11, 28, 29, W25, W16, W30, W31, and W32, and of the B series, 5, 7, 8, 12, 13, 14, 18, 27, W15, W16, W17, W21, W22, W35, W37, and W40. For most specificities, at least two antisera were used, and for many, three or more were used. The control population consisted of 342 random healthy individuals from the same region of the west of Scotland as the

patients.

,

Disturbances of

HLA

expected

antigen frequency

were

observed: HLA

Patients (15) (%)

Controls (342) (%)

Al A29 AW30 AW31 AW32 "AW19"* B8

S3.3 6.6 6-6 20 20 53.3 46.6

40.3

*Includes A29,

4.6 2.8 3.4 4.11 11.9

30.7

W30, W31, and Us’32.

high frequency of B8, in association with Al and other first-series antigens was striking. In addition we noticed a very unusual increase in the antigens of the "W19" group of A-series antigens (A29, AW30, AW31, and AW32). The

The

expected increase in Al with raised frequency of B8 (due to linkage disequilibrium) is also present. These observations correlate with findings in other disease states

in which T-cell function is believed

to

be abnormal (e.g.,

myasthenia gravis4 5). The abnormally high frequency of W19 specificities is not due to an association with B8 in these patients, and remains unexplained. We intend to extend our studies to a larger group of patients, doing more detailed 1. Lutzner, M., Edelson, R., Shein, T., Green, I., Kirkpatrick, C., Ahmed, A. Ann. intern. Med 1975, 83, 534. 2 Kissmeyer-Nielsen, F., Kjerbye, K. E. in Histocompatibility Testing 1967, p. 381. Copenhagen, 1967. 3. Dick, H. M., Crichton, W B., Ferguson-Smith, M A, Izatt, M. M. in Histocompatibility Testing 1972; p. 63. Copenhagen, 1972. 4. Behan, P O., Simpson, J. A., Dick, H. Lancet, 1973, ii, 1033, 1220. 5. Simpson, J. A. Ann. N. Y. Acad Sci. 1966, 135, 506

failed to advance from where I was thirteen years ago when I left this country to hold a chair in Australia. What I was trying to say by my remark that we should be "in there pitching" had no relation to salaries or conditions of service. Money, as one of my favourite novelists has said, is not but it buys nearly everything. Unfortunately, it is the second clause in that aphorism that seems to have come to dominate nearly all our thinking. Nevertheless, those of us who took up academic medicine must have felt that other things were more important than gold. Though these are indeed hard times for us all, we cannot deny that we are still at or very near the top of the salary bracket of all professional workers. True, we as academics have through a combination of self-neglect and maladroitness fallen behind relative to our peers (e.g., the Civil Service); but this does not detract from the fact that we are still comparatively well placed. What is far more important is that if one chooses an academic career one must face the fact that one is expected to do everything one’s non-academic colleagues do and much more besides for the same salary, as Professor Brumfitt and his colleagues have indicated. This is the academic’s doom, but of course with it come certain advantages which I need not detail but which are often pointed out to us by our N.H.S. counterparts. No, what I meant was that those whose commitment was to academic medicine in its broadest sense are still in a position to give some leadership; one direction that this can take in our increasingly materialistic world is leadership in values. Currently all debate seems to be centred on terms and conditions of service rather than the quality-and, it should be added, the quantity-of service that should be provided. What I am pleading for is that academic clinicians should put quality first and use their potential influence and undoubted intellectual powers to this end rather than join the majority in primarily deploring the circumstances in which we find ourselves. Professor Brumfitt and his colleagues may find this hopelessly outdated idealism but I sincerely believe that, unless we are prepared to provide much more of the lead in ideas and, almost

everything,

6 Zachiariae, H., Ellegaard, J, Grunnet, T., Søgaard, H., Thulin, H. Acta dern-vener. Stockh 1975, 55, 466. 7. MacKie, R., Sless, F. R , Cochran, R., de Sousa, M. Br J. Derm 1976, 96, 173.