- Email: [email protected]
LYMPHOID INFILTRATES IN SKIN IN GRAFT-VERSUS-HOST DISEASE
1352
peripheral monodeiodination to T3 will result in a raised T3 value. This additional estimation will not alter management, which should be to reduce the T4 dosage, and a case could well be made for the estimation of TSH in such cases to ensure that there had not been the possibility of erratic medication. The action limits for FTI and T4 do not agree with the adult reference range. It could be that the ranges quoted should be reviewed and modified to reflect more accurately the true range for a
euthyroid group. Department of Medicine, Freeman Hospital, Newcastle upon Tyne
F. CLARK
Department of Clinical Chemistry, Western General Hospital, Edinburgh
D. B. HORN
LYMPHOID INFILTRATES IN SKIN IN GRAFTVERSUS-HOST DISEASE
SIR,-Bone marrow transplantation is now frequently used to aplastic anaemia and leukaemia. The major cause of morbidity and mortality is graft-versus-host disease (GVHD), the most promi1 nent features of which are to be seen in the skin, bowel, and liver. Skin biopsy is the conventional diagnostic technique and is regarded as the most reliable method of establishing the diagnosis. in the skin can Unfortunately many of the milder features ofGVHD 2 treat
by irradiation and cytotoxic drugs. Recent immunohistochemical techniques, specifically the use of monoclonal antibodies directed against lymphoid subgroup antigens, allow the analysis of lymphoid infiltrates.3We have now applied this technique to the lymphoid infiltrates in GVHD. Samples of skin were snap frozen. Frozen sections were stained with anti-immunoglobulin (anti-Ig, to recognise membrane Ig on B cells), OKT4 (to identify T cells of inducer/helper type), OKT8 (for T cells of cytotoxic/suppressor type), and OKT3 (a pan-T reagent). The staining was detectedby indirect immunofluorescence with the use of fluorescein and rhodamine conjugated antibodies. Examination of lymphoid infiltrates in four cases showed that these were exclusively T cells (OKT3, SmIg-) and consisted of a virtually pure population of the OKT8+ OKT4 - subset (table). In normal lymphoid tissue and peripheral blood the ratio of inducer (OKT4+) to suppressoi/cytotoxic (OKT8) cells is approximately 2: 1.4 The infiltrate in lichen planus, a condition which has clinical and histopathological features similar to GVHD, also consists ofa mixed infiltrate of both OKT4 and OKT8cells (unpublished). Thus the observation of an exclusive population of OKT8cells in GVHD skin is a characteristic finding. + After bone marrow transplantation it is common to find OKTS cells in the peripheral blood, but even in these cases 10-35% of the be stimulated
ED, Storb R, Clift RA, et al. Bone marrow transplantation. N Engl Med J 1975; 292: 832-34. 2. Sale GE, Lerner KG, Barker EA, Schulman HM, Thomas ED. The skin biopsy in the diagnosis of acute graft versus host disease in man. Am J Pathol 1977; 89: 621-35. 3. Janossy G, Tidman N, Papageorgiou ES, Kung PC, Goldstein G. Distribution of T 1. Thomas
lymphocyte subsets in human bone marrow and thymus: an analysis with monoclonal antibodies. J Immunol 1981, 126: 1608-13. 4. Hoffman RA, Kung PC, Hansen WP, Goldstein G. Simple and rapid determination of human T lymphocytes and their subsets in peripheral blood. Proc Natl Acad Sci USA 1980; 77: 4914-17.
OKT8+ lymphocytes infiltrating dermis (D) and epidermis (ED; asterisk) in skin of patient 2. Arrows point to large OKT8blasts in deeper region. T cells express the OKT4 antigen (unpublished).5 Therefore the exclusive presence of OKT8 cells in the infiltrates ofGVHD skin (see figure) indicates a special homing of these cells. There is evidence that GVHD in the skin tends to occur at sites of viral exanthemas,and the lymphoid response to certain infections (e.g., Epstein-Barr virus and cytomegalovirus) involve predominantly OKT8cells.’It is possible therefore that in cases of GVHD viral infections may contribute to provoking the disease process. The suggestive evidence that this might be so has been seen in one of our cases (case 2), in which the skin disease followed an infection of varicella. Lymphocyte subset studies ir-. the skin already contribute to our understanding of the probable pathogenesis of these diseases and might provide diagnostically valuable observations. Further studies are now important with these techniques in a number of disorders such as viral infections and hypersensitivity reactions.
circulating
Department of Histopathology, Royal Postgraduate Medical School, London W12 0HS
I. A. LAMPERT A. J. SUITTERS
Department of Immunology, Royal Free Hospital School of Medicine, London NW3 2QG
G. JANOSSY J. A. THOMAS
Department of Haematology, Royal Postgraduate Medical School, London
S. PALMER E. GORDON SMITH
5. De Bruin HG, Astaldi A, Leupers T, et al. T lymphocyte characteristics in bone marrow-transplanted patients II Analysis with monoclonal antibodies J Immunol 1981; 127: 244-51. 6. Fenyk JR, Warkentin PI, Goltz RW, et al. Sclerodeimatous graft-versus-host disease limited to an area of measles exanthem Lancet 1978, i 472-73 7. Carney WP, Rubin PH, Hoffman RA, Hansen W P, Healey K, Hirsch MS Analysis of T lymphocyte subsets in cytomegalovirus mononucleosis J Immunol 1981, 126: 2114-16.
CLINICAL AND IMMUNOLOGICAL FEATURES IN THE SKIN IN PATIENTS WITH GVHD
+ + + = large numbers of cells ; + + =moderate numbers *Surface membrane immunoglobulin.
of cells;
+
=sparse
cells, occ=occasional cells;
0=none.
peripheral monodeiodination to T3 will result in a raised T3 value. This additional estimation will not alter management, which should be to reduce the T4 dosage, and a case could well be made for the estimation of TSH in such cases to ensure that there had not been the possibility of erratic medication. The action limits for FTI and T4 do not agree with the adult reference range. It could be that the ranges quoted should be reviewed and modified to reflect more accurately the true range for a
euthyroid group. Department of Medicine, Freeman Hospital, Newcastle upon Tyne
F. CLARK
Department of Clinical Chemistry, Western General Hospital, Edinburgh
D. B. HORN
LYMPHOID INFILTRATES IN SKIN IN GRAFTVERSUS-HOST DISEASE
SIR,-Bone marrow transplantation is now frequently used to aplastic anaemia and leukaemia. The major cause of morbidity and mortality is graft-versus-host disease (GVHD), the most promi1 nent features of which are to be seen in the skin, bowel, and liver. Skin biopsy is the conventional diagnostic technique and is regarded as the most reliable method of establishing the diagnosis. in the skin can Unfortunately many of the milder features ofGVHD 2 treat
by irradiation and cytotoxic drugs. Recent immunohistochemical techniques, specifically the use of monoclonal antibodies directed against lymphoid subgroup antigens, allow the analysis of lymphoid infiltrates.3We have now applied this technique to the lymphoid infiltrates in GVHD. Samples of skin were snap frozen. Frozen sections were stained with anti-immunoglobulin (anti-Ig, to recognise membrane Ig on B cells), OKT4 (to identify T cells of inducer/helper type), OKT8 (for T cells of cytotoxic/suppressor type), and OKT3 (a pan-T reagent). The staining was detectedby indirect immunofluorescence with the use of fluorescein and rhodamine conjugated antibodies. Examination of lymphoid infiltrates in four cases showed that these were exclusively T cells (OKT3, SmIg-) and consisted of a virtually pure population of the OKT8+ OKT4 - subset (table). In normal lymphoid tissue and peripheral blood the ratio of inducer (OKT4+) to suppressoi/cytotoxic (OKT8) cells is approximately 2: 1.4 The infiltrate in lichen planus, a condition which has clinical and histopathological features similar to GVHD, also consists ofa mixed infiltrate of both OKT4 and OKT8cells (unpublished). Thus the observation of an exclusive population of OKT8cells in GVHD skin is a characteristic finding. + After bone marrow transplantation it is common to find OKTS cells in the peripheral blood, but even in these cases 10-35% of the be stimulated
ED, Storb R, Clift RA, et al. Bone marrow transplantation. N Engl Med J 1975; 292: 832-34. 2. Sale GE, Lerner KG, Barker EA, Schulman HM, Thomas ED. The skin biopsy in the diagnosis of acute graft versus host disease in man. Am J Pathol 1977; 89: 621-35. 3. Janossy G, Tidman N, Papageorgiou ES, Kung PC, Goldstein G. Distribution of T 1. Thomas
lymphocyte subsets in human bone marrow and thymus: an analysis with monoclonal antibodies. J Immunol 1981, 126: 1608-13. 4. Hoffman RA, Kung PC, Hansen WP, Goldstein G. Simple and rapid determination of human T lymphocytes and their subsets in peripheral blood. Proc Natl Acad Sci USA 1980; 77: 4914-17.
OKT8+ lymphocytes infiltrating dermis (D) and epidermis (ED; asterisk) in skin of patient 2. Arrows point to large OKT8blasts in deeper region. T cells express the OKT4 antigen (unpublished).5 Therefore the exclusive presence of OKT8 cells in the infiltrates ofGVHD skin (see figure) indicates a special homing of these cells. There is evidence that GVHD in the skin tends to occur at sites of viral exanthemas,and the lymphoid response to certain infections (e.g., Epstein-Barr virus and cytomegalovirus) involve predominantly OKT8cells.’It is possible therefore that in cases of GVHD viral infections may contribute to provoking the disease process. The suggestive evidence that this might be so has been seen in one of our cases (case 2), in which the skin disease followed an infection of varicella. Lymphocyte subset studies ir-. the skin already contribute to our understanding of the probable pathogenesis of these diseases and might provide diagnostically valuable observations. Further studies are now important with these techniques in a number of disorders such as viral infections and hypersensitivity reactions.
circulating
Department of Histopathology, Royal Postgraduate Medical School, London W12 0HS
I. A. LAMPERT A. J. SUITTERS
Department of Immunology, Royal Free Hospital School of Medicine, London NW3 2QG
G. JANOSSY J. A. THOMAS
Department of Haematology, Royal Postgraduate Medical School, London
S. PALMER E. GORDON SMITH
5. De Bruin HG, Astaldi A, Leupers T, et al. T lymphocyte characteristics in bone marrow-transplanted patients II Analysis with monoclonal antibodies J Immunol 1981; 127: 244-51. 6. Fenyk JR, Warkentin PI, Goltz RW, et al. Sclerodeimatous graft-versus-host disease limited to an area of measles exanthem Lancet 1978, i 472-73 7. Carney WP, Rubin PH, Hoffman RA, Hansen W P, Healey K, Hirsch MS Analysis of T lymphocyte subsets in cytomegalovirus mononucleosis J Immunol 1981, 126: 2114-16.
CLINICAL AND IMMUNOLOGICAL FEATURES IN THE SKIN IN PATIENTS WITH GVHD
+ + + = large numbers of cells ; + + =moderate numbers *Surface membrane immunoglobulin.
of cells;
+
=sparse
cells, occ=occasional cells;
0=none.