1347 and oesophageal cancer (B40)6 have shown to be associated with specific HLA types but these malignancies have rather restricted racial distribution. Several aspects of testicular germ-cell tumours suggest genetic regulatory factors. First, the ethnic incidence varies widely: European and North American Whites have an incidence of approximately 2 per 1000 000,7 while the disease is very rare in American and African Blacks and in Japanese.8.9 Secondly, approximately 1% of the male mice of inbred strain 129 have spontaneous testicular teratomas,10 while in a subline of the strain, 32% of the males have teratomas.11 These tumours apparently arise from the primordial germ cells. Testicular tumours constitute the commonest epithelial solid malignancy after melanoma in North American males aged 20-30 years.8 Possible involvement of major-histocompatibility-complex encoded antigens in the differentiated events that take place in embryonal cells of mouse teratocarcinoma is suggested by the lack of the H-2 antigen (the mouse major histocompatibility complex), and possession instead of the foetal antigen, F9. The H-2 antigen is acquired when these cells undergo differentiation to teratomas.12 This prompted us to examine our patients with testicular teratocarcinoma for a possible association with an HLA antigen. 5 of our 20 patients (25%) possess the HLA-A locus antigen W24. All 5 had metastatic disease out of a total of 9 patients with distant involvement (55%). All the patients were of European descent. The frequency of AW24 antigen in the group as a whole is not significantly different from the normal frequency (16%) of this antigen in North American Whites.13 However, the frequency of antigen AW24 in patients with metastatic tumour was significantly increased (Fisher exact test, p=0.0075). The frequency of AW24 antigen in the metastatic group (5/9) is also greater than the frequency in the non-
metastatic group (0/11) (r=0-008). Our series is a small one and our interpretations must be preliminary. Furthermore, correction of the p value for the number of HLA antigens studied (20) eliminates the significance of the difference between the normal frequency and that found in patients with metastases. The comparison between metastatic and non-metastatic populations would not require correction for the number of antigens studied, although a conservative analysis might require a much lesser correction; the p (0-008) would probably still be significant. The concept of the association between HLA antigens and disease may help in the subdivision of what are considered single entities clinically. A possibly increased frequency of HLA-AW24 in patients with metastatic, non-seminomatous, testicular, germ-cell tumours requires further studies because of the small numbers studied. If our studies are confirmed it could be that in a patient with this form of tumour, the presence of the AW24 antigen might indicate an increased likelihood of distant involvement.
ABSENCE OF LYMPHOCYTOTOXIC ANTIBODIES IN SPOUSES OF MULTIPLE-SCLEROSIS PATIENTS
SIR, The report by Schocket and BX’einer1 that cold-reacting lymphocytotoxic antibodies (L.C.A.S) were as prevalent in 9 spouses of multiple sclerosis (M.S.) patients as in the patients themselves, is of considerable importance to the hypothesis that M.S. is associated with a transmissible agent. However, we have been unable to confirm Schocket and Weiner’s finding in a larger series. Sera from 62 Australian patients with definite M.S. (as defined by McAlpine’s criteria2 on clinical examination, including visual evoked responses), from 45 spouses of M.S. patients, and from 125 Canberra blood-donors, were screened for presence of L.C.A.Sby the microdroplet technique3 modified for 15°C conditions. Target cells were peripheral B lymphocytes from twelve normal donors. Most cold-reactive lymphocytotoxic sera recognise determinants on both B and T cells,4 but since a proportion of sera are selectively B or T-cell specific4 target cells were restricted to B-cell enriched preparations of known HLA DRw, A, and B specificities. The distribution of cytotoxicity was clearly bimodal in M.S. patients. The proportion of target cells killed in each microlymphocytotoxic test was scored on a five-point scale from 0-4 (less than 20% of target cells killed, 20-50%, 50-75%, 75-90%, or 90-100%). Mean cytotoxicity scores were determined from the simple mean of 12 cell reactions, and a score greater than 0.40 was considered evidence for the presence of L.C.A.S.
In
from
patients, the prevalence of L.c.A.s was comparable with an earlier figure of 34% L.C.A.S in a series of 400 M.S. patients but significantly lower (p
metastatic group (0/11) (r=0-008). Our series is a small one and our interpretations must be preliminary. Furthermore, correction of the p value for the number of HLA antigens studied (20) eliminates the significance of the difference between the normal frequency and that found in patients with metastases. The comparison between metastatic and non-metastatic populations would not require correction for the number of antigens studied, although a conservative analysis might require a much lesser correction; the p (0-008) would probably still be significant. The concept of the association between HLA antigens and disease may help in the subdivision of what are considered single entities clinically. A possibly increased frequency of HLA-AW24 in patients with metastatic, non-seminomatous, testicular, germ-cell tumours requires further studies because of the small numbers studied. If our studies are confirmed it could be that in a patient with this form of tumour, the presence of the AW24 antigen might indicate an increased likelihood of distant involvement.
ABSENCE OF LYMPHOCYTOTOXIC ANTIBODIES IN SPOUSES OF MULTIPLE-SCLEROSIS PATIENTS
SIR, The report by Schocket and BX’einer1 that cold-reacting lymphocytotoxic antibodies (L.C.A.S) were as prevalent in 9 spouses of multiple sclerosis (M.S.) patients as in the patients themselves, is of considerable importance to the hypothesis that M.S. is associated with a transmissible agent. However, we have been unable to confirm Schocket and Weiner’s finding in a larger series. Sera from 62 Australian patients with definite M.S. (as defined by McAlpine’s criteria2 on clinical examination, including visual evoked responses), from 45 spouses of M.S. patients, and from 125 Canberra blood-donors, were screened for presence of L.C.A.Sby the microdroplet technique3 modified for 15°C conditions. Target cells were peripheral B lymphocytes from twelve normal donors. Most cold-reactive lymphocytotoxic sera recognise determinants on both B and T cells,4 but since a proportion of sera are selectively B or T-cell specific4 target cells were restricted to B-cell enriched preparations of known HLA DRw, A, and B specificities. The distribution of cytotoxicity was clearly bimodal in M.S. patients. The proportion of target cells killed in each microlymphocytotoxic test was scored on a five-point scale from 0-4 (less than 20% of target cells killed, 20-50%, 50-75%, 75-90%, or 90-100%). Mean cytotoxicity scores were determined from the simple mean of 12 cell reactions, and a score greater than 0.40 was considered evidence for the presence of L.C.A.S.
In
from
patients, the prevalence of L.c.A.s was comparable with an earlier figure of 34% L.C.A.S in a series of 400 M.S. patients but significantly lower (p
