96 gress
to
examine the effect of
intrapleural
B.C.G.
in
macro-
phage depleted and immunosuppressed animals.
We believe that restoration of immune competence if possible, precede specific or non-specific treatment.
Cancer Research Campaign Laboratories,
University of Nottingham, University Park, Nottingham NG7 2RD
M. V. PIMM
Institute of Clinical Science and Research, Royal College of Surgeons in Ireland, Dublin, Eire
should,
ORLA BROWNE J. BELL P. D. J. HOLLAND R. D. THORNES
PLASMAPHERESIS AND IMMUNOSTIMULATION very interested in your editorial’ on the applications of plasmapheresis and in particular of its use by Hersey and his colleagues to remove serum blocking factors of cell-mediated immunity in patients with malignant melanoma. We have shown that T-lymphocyte activity can be enhanced in patients with malignant disease, including melanoma, by intravenous infusion of proteolytic enzymes (i.e., ’Brinase’2 and
SIR,-We
were
clinical
or by washing of lymphocytes removed by an I.B.M./N.C.I. continuous-flow cell separator.’ The enhancement of T-cell activity by these measures, however, lasts only
streptokinase3)
about four to seven days in advanced malignancy. The reblocking of activity, we presume, is due to serum blocking factors.
We found that the
use
of the cell
separator
alone without
washing of the lymphocytes enhanced T-cell activity in patients. We then demonstrated (unpublished) that simple mechanical agitation of blocked T cells from patients with malignant disease increases their capacity to bind sheep erythrocytes (E rosettes) and that the material shaken off the lymphocytes when incubated with normal control T cells inhibits their binding capacity: Cancer Breast
T cells (%) ’’Shakings’’ added to control T cells Before shaking After shaking Control (%) Reduced to (%)
Qaecum Lymphosarcoma
The T-cell
18 48 54
62 58 70 of healthy controls
50 74
35 67
70 unaffected
59
by shaking. Because of the blocking effect of serum factors on T cells in malignancy we subjected two patients with advanced malignant disease to plasmapheresis using the I.B.M. continuousflow cell separator, 2 litres of patient’s plasma being exchanged for a similar amount of fresh-frozen pooled human plasma. The patient’s T-cell counts rose from 30% to 58% (case 1) and from 34% to 75% (case 2) following the procedure. The serum blocking effect on control normal T cells fell appreciably immediately after plasmapheresis and remained at a low level in each case for about 4 weeks. Normal control T cells were incubated in patient’s serum for 30 min at 18°C. The serum blocking effect was then expressed as the percentage reduction in E counts
were
rosetting: % reduction in E rosetting Time
Before plasmapheresis After plasmapheresis: 1 wk 2 wk 3 wk 4 wk
Case 1
Case 2
(osteosarcoma)
(bronchogemc carcinoma)
34 7 3 4 2 22
50 24 17 18 16 15
Repeat plasmapheresis: 1 wk later 2 wk later Skin hypersensitivity
6 16 to dmitrochlorobenzene and was restored in both patients.
4 11
punfied protein derivative but streptokinase In these two cases the relatively small exchange of 2 litres was sufficient to produce a prolonged effect. If this experience is confirmed in a larger series of patients which we are now investigating then plasmapheresis could have a practical part to play in immunotherapy.
not to
ENHANCED ANTIBODY RESPONSES IN ACTIVE CHRONIC HEPATITIS
SIR,—We read the paper by Galbraith et al.’ with interest. We have done similar studies but our results differ in several respects. Galbraith et al. found a significant correlation between raised antibody titres to rubella and to measles and the possession of HLA-B8 in patients with HBsAg-negative chronic active hepatitis, but not in their relatives. We have studied antibodies to a variety of antigens including rubella and measles in individually matched HLA-B8 positive and negative subjects-mainly patients with HBsAg-negative chronic liver disease, including many with chronic active hepatitis-and found no correlation between HLA-B8 and any antibody titre except gluten.2 Furthermore, in a separate unpublished study of 33 patients with HBsAg-negative chronic active hepatitis we found no correlation between HLA-B8 and rubella or measles antibody titres. We were careful in our published study2 to match individually the HLA-B8 positive and negative subjects, especially for age, since we find in adult controls an inverse correlation between these antibody titres (notably rubella, P
to
examine the effect of
intrapleural
B.C.G.
in
macro-
phage depleted and immunosuppressed animals.
We believe that restoration of immune competence if possible, precede specific or non-specific treatment.
Cancer Research Campaign Laboratories,
University of Nottingham, University Park, Nottingham NG7 2RD
M. V. PIMM
Institute of Clinical Science and Research, Royal College of Surgeons in Ireland, Dublin, Eire
should,
ORLA BROWNE J. BELL P. D. J. HOLLAND R. D. THORNES
PLASMAPHERESIS AND IMMUNOSTIMULATION very interested in your editorial’ on the applications of plasmapheresis and in particular of its use by Hersey and his colleagues to remove serum blocking factors of cell-mediated immunity in patients with malignant melanoma. We have shown that T-lymphocyte activity can be enhanced in patients with malignant disease, including melanoma, by intravenous infusion of proteolytic enzymes (i.e., ’Brinase’2 and
SIR,-We
were
clinical
or by washing of lymphocytes removed by an I.B.M./N.C.I. continuous-flow cell separator.’ The enhancement of T-cell activity by these measures, however, lasts only
streptokinase3)
about four to seven days in advanced malignancy. The reblocking of activity, we presume, is due to serum blocking factors.
We found that the
use
of the cell
separator
alone without
washing of the lymphocytes enhanced T-cell activity in patients. We then demonstrated (unpublished) that simple mechanical agitation of blocked T cells from patients with malignant disease increases their capacity to bind sheep erythrocytes (E rosettes) and that the material shaken off the lymphocytes when incubated with normal control T cells inhibits their binding capacity: Cancer Breast
T cells (%) ’’Shakings’’ added to control T cells Before shaking After shaking Control (%) Reduced to (%)
Qaecum Lymphosarcoma
The T-cell
18 48 54
62 58 70 of healthy controls
50 74
35 67
70 unaffected
59
by shaking. Because of the blocking effect of serum factors on T cells in malignancy we subjected two patients with advanced malignant disease to plasmapheresis using the I.B.M. continuousflow cell separator, 2 litres of patient’s plasma being exchanged for a similar amount of fresh-frozen pooled human plasma. The patient’s T-cell counts rose from 30% to 58% (case 1) and from 34% to 75% (case 2) following the procedure. The serum blocking effect on control normal T cells fell appreciably immediately after plasmapheresis and remained at a low level in each case for about 4 weeks. Normal control T cells were incubated in patient’s serum for 30 min at 18°C. The serum blocking effect was then expressed as the percentage reduction in E counts
were
rosetting: % reduction in E rosetting Time
Before plasmapheresis After plasmapheresis: 1 wk 2 wk 3 wk 4 wk
Case 1
Case 2
(osteosarcoma)
(bronchogemc carcinoma)
34 7 3 4 2 22
50 24 17 18 16 15
Repeat plasmapheresis: 1 wk later 2 wk later Skin hypersensitivity
6 16 to dmitrochlorobenzene and was restored in both patients.
4 11
punfied protein derivative but streptokinase In these two cases the relatively small exchange of 2 litres was sufficient to produce a prolonged effect. If this experience is confirmed in a larger series of patients which we are now investigating then plasmapheresis could have a practical part to play in immunotherapy.
not to
ENHANCED ANTIBODY RESPONSES IN ACTIVE CHRONIC HEPATITIS
SIR,—We read the paper by Galbraith et al.’ with interest. We have done similar studies but our results differ in several respects. Galbraith et al. found a significant correlation between raised antibody titres to rubella and to measles and the possession of HLA-B8 in patients with HBsAg-negative chronic active hepatitis, but not in their relatives. We have studied antibodies to a variety of antigens including rubella and measles in individually matched HLA-B8 positive and negative subjects-mainly patients with HBsAg-negative chronic liver disease, including many with chronic active hepatitis-and found no correlation between HLA-B8 and any antibody titre except gluten.2 Furthermore, in a separate unpublished study of 33 patients with HBsAg-negative chronic active hepatitis we found no correlation between HLA-B8 and rubella or measles antibody titres. We were careful in our published study2 to match individually the HLA-B8 positive and negative subjects, especially for age, since we find in adult controls an inverse correlation between these antibody titres (notably rubella, P
