- Email: [email protected]
IN-VITRO IMMUNOLOGICAL ASSAY FOR DIAGNOSIS OF CŒLIAC DISEASE
876 theoretical nor experimental evidence to support its use and demands large resources of valuable blood-products. In paraquat poisoning, rational treatment-namely, gastrointestinal absorbents and hxmodialysis/perfusion-is already available. These treatments may require sophisticated apparatus but the economic drain in their use is probably less than for plasma-
pheresis.
Their location incertain
specialised
units has the
additional advantage of allowing the study of sufficient numbers of patients to expand our knowledge of paraquat
pharmacokinetics and treatment. K.R.U.F. Institute of Renal
J. MILLER
Disease,
E. SANDERS
Royal Infirmary,
D. WEBB
Z Cardiff CF2 15
IN-VITRO IMMUNOLOGICAL ASSAY FOR DIAGNOSIS OF CŒLIAC DISEASE
interested in the paper by Dr Ashkenazi and colleagues (March 25, p. 627) on the production of leucocytemigration-inhibition factor (L.LF.) by codiac peripheral-blood lymphocytes challenged in vitro with a gluten fraction. Their patients were essentially children; earlier reportsl-5 of gluteninduced L.I.F. release by leucocytes have been based on work on adults with coeliac disease. To date, reports have consistently shown the specificity of this leucocyte migration inhibition (L.M.I.) with respect to coeliac disease, but, with one exception,3 have failed to assess its specificity in terms of other dietary
SIR,-We
were
antigens. FREQUENCY
OF L.M.I. TO THREE ANTIGENS IN C(ELM
OTHER GASTROINTESTINAL
DISEASE,
DISEASE,
AND CONTROLS
*For of-gliadin, migration inhibition was taken as a mean migration index (6 replicates per antigen dilution) below the 2 s.D. range (0.89-1.25) derived from the healthy staff control group. For oc-lactalbumin and a.c.., a migration index below 0.80 was considered to represent significant inhibition.
We have looked at both the antigen and disease specificity of this in-vitro assay system.6 L.M.I. to ot-giiadin, a-lactalbumin, and B.C.G. has been studied in five groups (table), including untreated coeliacs ingesting a normal diet and coeliacs who had been on a strict gluten-free diet for over 6 months. L.M.I. to B.C.G. was similar in all groups, confirming the potentially normal responsiveness of coeliac leucocytes in this test. L.M.I. to an a-gliadin fraction known to be toxic to cceliac patients in remission’ was virtually specific for coeliac disease. While these differences between coeliacs and other subjects could result from non-specific intestinal permeability to many dietary antigens secondary to the villous atrophy, this seems unlikely in view of the absence of any significant differences in the fre1. Bullen, A. W., Losowsky, M. S. Gut, 1976, 17, 813. 2. Douwes, F. R. Lancet, 1976, ii, 1353. 3. Asquith, P., Haeney, M. R. Gut, 1977, 18, A942. 4. Douwes, F. R., Lippmann-Nielsen, I., Hanke, R. Dt. med. Wschr. 1977,
102, 721. 5. Bullen, A. W., Losowsky, M. S. Gut, 1978, 19, 126. 6. Haeney, M. R., Asquith, P. in Perspectives in Coeliac Disease (edited by B. McNicholl, C. F. McCarthy, and P. F. Fottrell). Lancaster (in the press). 7. Schneider, R., Kendall, M. J., Hawkins, C. F. in Cœliac Disease: Proceedmgs of the Second International Cœliac Symposium (edited by W. Th. J. M. Hekkens and A. S. Peña); p. 72. Leiden, 1974.
quency of
L.M.I. to a-lactalbumin. Our results are in broad with those of Ashkenazi et al. but additionally sugagreement gest that L.M.I. is likely to be specific for a-gliadin. However, our findings do differ in one interesting respect. We found that L.M.I. to ot-gliadin was more common in treated than in untreated coeliacs, and have suggested that this may be due to a redistribution of lymphocytes after antigen withdrawal. A similar hypothesis was proposed to explain comparable results of lymphocyte transformation by gluten in cceliacs ingesting normal or gluten-free diets.8 L.M.I. to a-gliadin may be due to factors other than L.LF. generated by the activation of sensitised T lymphocytes, including antigen-antibody complexes9 or L.I.F. release by B cells.1o Despite these alternative explanations, L.M.I. to antigenic challenge shows a qualitative correlation with in-vivo cell-mediated immunity in the host.
Regional Immunology Unit, and Metabolic Research Unit, East Birmingham Hospital, Birmingham B9 5ST
M. R. HAENEY
P. ASQUITH
BONE-MARROW TRANSPLANTATION IN ACUTE LEUKÆMIA
SIR,-Commenting upon the report by the U.C.L.A. BoneTransplant Team,’ Dr Catovsky and his colleagues (Feb. 4, p. 266) ask "Did the controls receive the most intensive treatment, short of total-body irradiation, that could be safely administered without the support of a marrow graft?". marrow
This
cannot be answered: if the patient did not surthe was obviously too intensive, but if the patreatment vive, tient lives there is no way to know whether or not more therapy could have been tolerated. The principal objective of the marrow-transplantation approach is the administration of "supralethal" antileukaemic therapy with subsequent avoidance of death from marrow aplasia by transplantation of a "new" bone-marrow. We have reported long-term survival in patients with relapsed acute leukaemia, both lymphoblastic and myeloid, treated by intensive chemotherapy, total-body irradiation, and bone-marrow transplantation.2,6of 16 recipients of syngeneic marrow and 14 of 110 recipients of allogeneic marrow are still alive, without leukaemia, 2t to 7y years later. Actuarial analysis4 of the probability of being in remission indicated a constant rate of relapse for the first 2 years. Thereafter, the relapse-rate became very low, indicating a high probability that these long-term survivors are cured of their diseaseespecially since all the living patients are well out on the plateau of the curve. Powles6 has pointed out that a similar analysis of patients treated with chemotherapy shows a continued risk of relapse with time measured over years. Of course, with a constant rate of relapse (or death) there would always be a few long-term survivors if one starts with a sufficiently large number of patients. An actuarial analysis of survival after first relapse of the 150 patients mentioned by Catovsky et al. would be of interest.
question
Fred Hutchinson Cancer Research Center, Seattle, Washington 98104, U.S.A.
E. DONNALL THOMAS
8. Asquith, P. ibid. p. 242. 9. Spitler, L., Huber, H., Fudenberg, H. H. J. Immun. 1969, 102, 404. 10. Rocklin, R. E., MacDermott, R. P., Chess, L., Schlossman, S. F., David, J. R. J. exp. Med. 1974, 140, 1303. 11. David, J. R., David, R. R. Progr. Allergy, 1972, 16, 300. 1. U.C.L.A. Bone-marrow Transplant Team Lancet, 1977, ii, 1197. 2. Thomas, E. D., and others Blood, 1977, 49, 511. 3. Fefer, A., Buckner, C. D., Thomas, E. D., Cheever, M. A., Clift, R. A., Glucksberg, H., Neiman, P. E., Storb, R. New Engl. J. Med. 1977, 297, 146. 4. Kaplan, E. L., Meier, P. J. Am. statist. Ass. 1958, 53, 457. 5. Thomas, E. D., Flournoy, N., Buckner, C. D., Clift, R. A., Fefer, A., Neiman, P. E., Storb, R. Leukemia Res. 1977, 1, 67. 6. Powles, R. L. Biomedicine, 1976, 24, 327.
pheresis.
Their location incertain
specialised
units has the
additional advantage of allowing the study of sufficient numbers of patients to expand our knowledge of paraquat
pharmacokinetics and treatment. K.R.U.F. Institute of Renal
J. MILLER
Disease,
E. SANDERS
Royal Infirmary,
D. WEBB
Z Cardiff CF2 15
IN-VITRO IMMUNOLOGICAL ASSAY FOR DIAGNOSIS OF CŒLIAC DISEASE
interested in the paper by Dr Ashkenazi and colleagues (March 25, p. 627) on the production of leucocytemigration-inhibition factor (L.LF.) by codiac peripheral-blood lymphocytes challenged in vitro with a gluten fraction. Their patients were essentially children; earlier reportsl-5 of gluteninduced L.I.F. release by leucocytes have been based on work on adults with coeliac disease. To date, reports have consistently shown the specificity of this leucocyte migration inhibition (L.M.I.) with respect to coeliac disease, but, with one exception,3 have failed to assess its specificity in terms of other dietary
SIR,-We
were
antigens. FREQUENCY
OF L.M.I. TO THREE ANTIGENS IN C(ELM
OTHER GASTROINTESTINAL
DISEASE,
DISEASE,
AND CONTROLS
*For of-gliadin, migration inhibition was taken as a mean migration index (6 replicates per antigen dilution) below the 2 s.D. range (0.89-1.25) derived from the healthy staff control group. For oc-lactalbumin and a.c.., a migration index below 0.80 was considered to represent significant inhibition.
We have looked at both the antigen and disease specificity of this in-vitro assay system.6 L.M.I. to ot-giiadin, a-lactalbumin, and B.C.G. has been studied in five groups (table), including untreated coeliacs ingesting a normal diet and coeliacs who had been on a strict gluten-free diet for over 6 months. L.M.I. to B.C.G. was similar in all groups, confirming the potentially normal responsiveness of coeliac leucocytes in this test. L.M.I. to an a-gliadin fraction known to be toxic to cceliac patients in remission’ was virtually specific for coeliac disease. While these differences between coeliacs and other subjects could result from non-specific intestinal permeability to many dietary antigens secondary to the villous atrophy, this seems unlikely in view of the absence of any significant differences in the fre1. Bullen, A. W., Losowsky, M. S. Gut, 1976, 17, 813. 2. Douwes, F. R. Lancet, 1976, ii, 1353. 3. Asquith, P., Haeney, M. R. Gut, 1977, 18, A942. 4. Douwes, F. R., Lippmann-Nielsen, I., Hanke, R. Dt. med. Wschr. 1977,
102, 721. 5. Bullen, A. W., Losowsky, M. S. Gut, 1978, 19, 126. 6. Haeney, M. R., Asquith, P. in Perspectives in Coeliac Disease (edited by B. McNicholl, C. F. McCarthy, and P. F. Fottrell). Lancaster (in the press). 7. Schneider, R., Kendall, M. J., Hawkins, C. F. in Cœliac Disease: Proceedmgs of the Second International Cœliac Symposium (edited by W. Th. J. M. Hekkens and A. S. Peña); p. 72. Leiden, 1974.
quency of
L.M.I. to a-lactalbumin. Our results are in broad with those of Ashkenazi et al. but additionally sugagreement gest that L.M.I. is likely to be specific for a-gliadin. However, our findings do differ in one interesting respect. We found that L.M.I. to ot-gliadin was more common in treated than in untreated coeliacs, and have suggested that this may be due to a redistribution of lymphocytes after antigen withdrawal. A similar hypothesis was proposed to explain comparable results of lymphocyte transformation by gluten in cceliacs ingesting normal or gluten-free diets.8 L.M.I. to a-gliadin may be due to factors other than L.LF. generated by the activation of sensitised T lymphocytes, including antigen-antibody complexes9 or L.I.F. release by B cells.1o Despite these alternative explanations, L.M.I. to antigenic challenge shows a qualitative correlation with in-vivo cell-mediated immunity in the host.
Regional Immunology Unit, and Metabolic Research Unit, East Birmingham Hospital, Birmingham B9 5ST
M. R. HAENEY
P. ASQUITH
BONE-MARROW TRANSPLANTATION IN ACUTE LEUKÆMIA
SIR,-Commenting upon the report by the U.C.L.A. BoneTransplant Team,’ Dr Catovsky and his colleagues (Feb. 4, p. 266) ask "Did the controls receive the most intensive treatment, short of total-body irradiation, that could be safely administered without the support of a marrow graft?". marrow
This
cannot be answered: if the patient did not surthe was obviously too intensive, but if the patreatment vive, tient lives there is no way to know whether or not more therapy could have been tolerated. The principal objective of the marrow-transplantation approach is the administration of "supralethal" antileukaemic therapy with subsequent avoidance of death from marrow aplasia by transplantation of a "new" bone-marrow. We have reported long-term survival in patients with relapsed acute leukaemia, both lymphoblastic and myeloid, treated by intensive chemotherapy, total-body irradiation, and bone-marrow transplantation.2,6of 16 recipients of syngeneic marrow and 14 of 110 recipients of allogeneic marrow are still alive, without leukaemia, 2t to 7y years later. Actuarial analysis4 of the probability of being in remission indicated a constant rate of relapse for the first 2 years. Thereafter, the relapse-rate became very low, indicating a high probability that these long-term survivors are cured of their diseaseespecially since all the living patients are well out on the plateau of the curve. Powles6 has pointed out that a similar analysis of patients treated with chemotherapy shows a continued risk of relapse with time measured over years. Of course, with a constant rate of relapse (or death) there would always be a few long-term survivors if one starts with a sufficiently large number of patients. An actuarial analysis of survival after first relapse of the 150 patients mentioned by Catovsky et al. would be of interest.
question
Fred Hutchinson Cancer Research Center, Seattle, Washington 98104, U.S.A.
E. DONNALL THOMAS
8. Asquith, P. ibid. p. 242. 9. Spitler, L., Huber, H., Fudenberg, H. H. J. Immun. 1969, 102, 404. 10. Rocklin, R. E., MacDermott, R. P., Chess, L., Schlossman, S. F., David, J. R. J. exp. Med. 1974, 140, 1303. 11. David, J. R., David, R. R. Progr. Allergy, 1972, 16, 300. 1. U.C.L.A. Bone-marrow Transplant Team Lancet, 1977, ii, 1197. 2. Thomas, E. D., and others Blood, 1977, 49, 511. 3. Fefer, A., Buckner, C. D., Thomas, E. D., Cheever, M. A., Clift, R. A., Glucksberg, H., Neiman, P. E., Storb, R. New Engl. J. Med. 1977, 297, 146. 4. Kaplan, E. L., Meier, P. J. Am. statist. Ass. 1958, 53, 457. 5. Thomas, E. D., Flournoy, N., Buckner, C. D., Clift, R. A., Fefer, A., Neiman, P. E., Storb, R. Leukemia Res. 1977, 1, 67. 6. Powles, R. L. Biomedicine, 1976, 24, 327.