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CD4+ T-CELL DAMAGE TO ISLET BETA CELLS
329 critical elements in the development of that patient’s central pontine myelinolysis. In otherwise healthy schizophrenic patients (including those with a history of alcohol abuse), targeted fluid
restriction for
preventing
at
the
least 16 hours is a safe and effective means of and mortality associated with water
morbidity
intoxication. University of Chicago Medical Center, Chicago, Ilinois 60637, USA; and Illinois State Psychiatric Institute, Chicago
MORRIS B. GOLDMAN DANIEL J. LUCHINS GARY L. ROBERTSON
1 Goldman MB, Luchins DJ, Robertson GL. Mechanisms of altered water metabolism m psychotic patients with polydipsia and hyponatremia. N Eegl J Med 1988; 318: 397-403 2. Goldman MB, Luchins DJ. Prevention of episodic water intoxication with target weight procedure. Am J Psychiatry 1987; 144: 365-66. 3 Ashby YT Planned change: the development of a program for the management of self-induced water intoxication. Can J Psychiatr Nurs 1987, 28: 12-14. 4. Delva NJ, Crammer JL Polydipsia in chronic psychiatric patients: body weight and J plasma sodium. Br Psychiatry 1988; 144: 1626. 5 Ripley TL, Millson RC, Kocapski AB. Self-induced water intoxication and alcohol abuse Am J Psychiatry 1989; 146: 101-02.
THE WHITE-COAT EFFECT AND SELF-RECORDING OF BLOOD PRESSURE
SIR,-Self-recording of blood pressure at home is of increasing importance in the management of hypertension. With multiple measurements knowledge of an individual’s average blood pressure is improved and, more importantly, the physician is no longer at risk of treating a condition evoked by himself-the so-called white-coat effect. We observed in a large group of patients accustomed to self-recording that the physician-induced blood pressure rise diminished with time. To study this effect in more detail, we randomly assigned 16 hypertensive patients (8 female, 8 male; age 58 [SD 3] years) to trained self-recording or "passive" control groups. All patients’ blood pressures were first measured by a physician in the clinic and the patients were maintained on their usual drugs for two weeks. Then the same physician repeated the measurement at the same time of day and in the same surroundings; self-recording patients presented their records with blood pressure measurements done three times daily. As expected, the average self-recorded blood pressure levels were significantly lower than the physician’s first result. Interestingly, in this group the physician’s second blood pressure result was also significantly diminished (161 [SD 5]/96 [4] vs 150 [4]/87 [4] mmHg, p < 0.05) and did not differ from the patients’ averages. In the controls there was no such effect (161 [5]/93 [3] vs 162 [6]/94 [3] mm Hg). To interpret this result in a small group of patients the possible effects of actively involving patients in the management of their condition have to be considered and studied separately. It would be interesting to see, over one or more years, whether there is a lessening of the self-recording effect on blood pressure in the clinic and the "white coat" supervenes after all. Second Department of Internal Medicine,
University of Vienna, A-1090 Vienna, Austria
BRIDGITTE STANEK ULRIKE BRUCKNER
CD4+ T-CELL DAMAGE TO ISLET BETA CELLS
cannot
rule
cells. Islet target cells, from two donors (HP72, HP73) were cultured for 2 days in presence of 50 U/ml each of IFNy and TNFa, to induce HLA class II antigens. Class II expression was confirmed by immunostaining with monoclonal antibody L243. HLA phenotype of diabetic patient was A2 B8,62 DR1,3. Cytotoxicity assay was done as previously described.
We report here another experiment with class II DR haploidentical islets which were lysed, and class II incompatible islets which were not (figure). These data accord with our previous report. Haskins et all published an account of a CD4 T cell clone from the non-obese diabetic mouse which was specific for islet cell preparations and mediated the destruction of islet P cells in syngeneic mice. Vento and Garofano point out that our results are at
variance with their stated claim that the "majority of T cells surrounding affected islets are CD8 + ". This claim is exaggerated; Bottazzo’s report2 was from a single patient coming to necropsy who had "mainly CD8cells but CD4cells were also present". There is no mention of CD8 cells in the Foulis and Farquarson3 paper cited. Vento et a14 have used the lymphocyte-migration inhibitory factor assay to study immune regulation in hepatitis B and urges us to do this for type I diabetes. We think that the analysis of T cell clones from patients (raised from single cells) is a better tool to dissect the complexity of the immune system. We would like to investigate patients in the prediabetic period (ie, before the onset of the disease process) but there is no reliable method to detect such individuals. Unlike hepatitis B, type I diabetes is a disease of unknown aetiology, and to suggest a list of probable antigens is to complicate an already difficult field. Vento and Garofano suggest that CD8+ suppressor cells may recognise class II positive cells, and they cite a recent symposium presentation. The suppressor cell literature is in considerable disarray,s and we cannot comment on unpublished presentations. Medical Clinic I, Universitá la Sapienza, Rome,
Italy
P. DE BERARDINIS
Charing Cross Sunley Research Centre
M. LONDEI
Department of Surgery, Leicester Royal Infirmary
R. F. L. JAMES S. P. LAKE
Department of Endocrinology, Charing Cross Hospital
P. H. WISE
Charing Cross Sunley Research Centre, Lurgan Avenue,
SIR,-Dr Vento and Dr Garofano (Nov 19, p 1200) discuss our study of CD4+ cytotoxic T cell damage to islet p cells in type I diabetes (Oct 8, p 823). Our results were unexpected and the report was preliminary. We did not rule out other mechanisms of islet cell damage. Because of the shortage of histocompatible human pancreatic islets, we could do only two experiments (not one, as Vento and Garofano state) with three Vp8 positive T cell clones from a newly diagnosed type I diabetic patient. Histocompatibility was achieved only with respect to HLA DR3 and possibly other class II antigens and not class I antigens, and for this reason, and because of the limited number of clones tested, we the killing of p cells by CD8cytotoxic T cells.
Lysis by CD4clone of HLA class II induced histocompatible islet
out
London W6 8LW
M. FELDMANN
1. Haskins
K, Portas M, Bradley B, Wegmann D, Lafferty K. T-lymphocyte clone specific for pancreatic islet antigen Diabetes 1988; 37: 1444-48. 2. Bottazzo GF, Dean BM, McNally JM, Mackay EH, Swift PGF, Gamble DR. In situ characterisation of autoimmune phenomena and expression of HLA molecules in pancreas in diabetic insulinitis. N Engl J Med 1985; 313: 353-60. 3. Foulis AK, Farquharson MA. Aberrant expression of HLA-DR antigens by insulin containing beta cells in recent onset type I diabetes mellitus. Diabetes 1986; 35: 1215-24. 4. Vento S, Rondanelli EG, Raneiri S, O’Brien CJ, Williams R, Eddleston ALWF. Prospective study of cellular immunity to hepatitis-B-virus antigens from the early incubation phase of acute hepatitis B. Lancet 1987; ii: 119-22. 5 Moller G. Do suppressor T cells exist? Scand J Immunol 1988, 27: 247-50.
restriction for
preventing
at
the
least 16 hours is a safe and effective means of and mortality associated with water
morbidity
intoxication. University of Chicago Medical Center, Chicago, Ilinois 60637, USA; and Illinois State Psychiatric Institute, Chicago
MORRIS B. GOLDMAN DANIEL J. LUCHINS GARY L. ROBERTSON
1 Goldman MB, Luchins DJ, Robertson GL. Mechanisms of altered water metabolism m psychotic patients with polydipsia and hyponatremia. N Eegl J Med 1988; 318: 397-403 2. Goldman MB, Luchins DJ. Prevention of episodic water intoxication with target weight procedure. Am J Psychiatry 1987; 144: 365-66. 3 Ashby YT Planned change: the development of a program for the management of self-induced water intoxication. Can J Psychiatr Nurs 1987, 28: 12-14. 4. Delva NJ, Crammer JL Polydipsia in chronic psychiatric patients: body weight and J plasma sodium. Br Psychiatry 1988; 144: 1626. 5 Ripley TL, Millson RC, Kocapski AB. Self-induced water intoxication and alcohol abuse Am J Psychiatry 1989; 146: 101-02.
THE WHITE-COAT EFFECT AND SELF-RECORDING OF BLOOD PRESSURE
SIR,-Self-recording of blood pressure at home is of increasing importance in the management of hypertension. With multiple measurements knowledge of an individual’s average blood pressure is improved and, more importantly, the physician is no longer at risk of treating a condition evoked by himself-the so-called white-coat effect. We observed in a large group of patients accustomed to self-recording that the physician-induced blood pressure rise diminished with time. To study this effect in more detail, we randomly assigned 16 hypertensive patients (8 female, 8 male; age 58 [SD 3] years) to trained self-recording or "passive" control groups. All patients’ blood pressures were first measured by a physician in the clinic and the patients were maintained on their usual drugs for two weeks. Then the same physician repeated the measurement at the same time of day and in the same surroundings; self-recording patients presented their records with blood pressure measurements done three times daily. As expected, the average self-recorded blood pressure levels were significantly lower than the physician’s first result. Interestingly, in this group the physician’s second blood pressure result was also significantly diminished (161 [SD 5]/96 [4] vs 150 [4]/87 [4] mmHg, p < 0.05) and did not differ from the patients’ averages. In the controls there was no such effect (161 [5]/93 [3] vs 162 [6]/94 [3] mm Hg). To interpret this result in a small group of patients the possible effects of actively involving patients in the management of their condition have to be considered and studied separately. It would be interesting to see, over one or more years, whether there is a lessening of the self-recording effect on blood pressure in the clinic and the "white coat" supervenes after all. Second Department of Internal Medicine,
University of Vienna, A-1090 Vienna, Austria
BRIDGITTE STANEK ULRIKE BRUCKNER
CD4+ T-CELL DAMAGE TO ISLET BETA CELLS
cannot
rule
cells. Islet target cells, from two donors (HP72, HP73) were cultured for 2 days in presence of 50 U/ml each of IFNy and TNFa, to induce HLA class II antigens. Class II expression was confirmed by immunostaining with monoclonal antibody L243. HLA phenotype of diabetic patient was A2 B8,62 DR1,3. Cytotoxicity assay was done as previously described.
We report here another experiment with class II DR haploidentical islets which were lysed, and class II incompatible islets which were not (figure). These data accord with our previous report. Haskins et all published an account of a CD4 T cell clone from the non-obese diabetic mouse which was specific for islet cell preparations and mediated the destruction of islet P cells in syngeneic mice. Vento and Garofano point out that our results are at
variance with their stated claim that the "majority of T cells surrounding affected islets are CD8 + ". This claim is exaggerated; Bottazzo’s report2 was from a single patient coming to necropsy who had "mainly CD8cells but CD4cells were also present". There is no mention of CD8 cells in the Foulis and Farquarson3 paper cited. Vento et a14 have used the lymphocyte-migration inhibitory factor assay to study immune regulation in hepatitis B and urges us to do this for type I diabetes. We think that the analysis of T cell clones from patients (raised from single cells) is a better tool to dissect the complexity of the immune system. We would like to investigate patients in the prediabetic period (ie, before the onset of the disease process) but there is no reliable method to detect such individuals. Unlike hepatitis B, type I diabetes is a disease of unknown aetiology, and to suggest a list of probable antigens is to complicate an already difficult field. Vento and Garofano suggest that CD8+ suppressor cells may recognise class II positive cells, and they cite a recent symposium presentation. The suppressor cell literature is in considerable disarray,s and we cannot comment on unpublished presentations. Medical Clinic I, Universitá la Sapienza, Rome,
Italy
P. DE BERARDINIS
Charing Cross Sunley Research Centre
M. LONDEI
Department of Surgery, Leicester Royal Infirmary
R. F. L. JAMES S. P. LAKE
Department of Endocrinology, Charing Cross Hospital
P. H. WISE
Charing Cross Sunley Research Centre, Lurgan Avenue,
SIR,-Dr Vento and Dr Garofano (Nov 19, p 1200) discuss our study of CD4+ cytotoxic T cell damage to islet p cells in type I diabetes (Oct 8, p 823). Our results were unexpected and the report was preliminary. We did not rule out other mechanisms of islet cell damage. Because of the shortage of histocompatible human pancreatic islets, we could do only two experiments (not one, as Vento and Garofano state) with three Vp8 positive T cell clones from a newly diagnosed type I diabetic patient. Histocompatibility was achieved only with respect to HLA DR3 and possibly other class II antigens and not class I antigens, and for this reason, and because of the limited number of clones tested, we the killing of p cells by CD8cytotoxic T cells.
Lysis by CD4clone of HLA class II induced histocompatible islet
out
London W6 8LW
M. FELDMANN
1. Haskins
K, Portas M, Bradley B, Wegmann D, Lafferty K. T-lymphocyte clone specific for pancreatic islet antigen Diabetes 1988; 37: 1444-48. 2. Bottazzo GF, Dean BM, McNally JM, Mackay EH, Swift PGF, Gamble DR. In situ characterisation of autoimmune phenomena and expression of HLA molecules in pancreas in diabetic insulinitis. N Engl J Med 1985; 313: 353-60. 3. Foulis AK, Farquharson MA. Aberrant expression of HLA-DR antigens by insulin containing beta cells in recent onset type I diabetes mellitus. Diabetes 1986; 35: 1215-24. 4. Vento S, Rondanelli EG, Raneiri S, O’Brien CJ, Williams R, Eddleston ALWF. Prospective study of cellular immunity to hepatitis-B-virus antigens from the early incubation phase of acute hepatitis B. Lancet 1987; ii: 119-22. 5 Moller G. Do suppressor T cells exist? Scand J Immunol 1988, 27: 247-50.