Teruyuki Takamatsu

The Serum Cytokine Profiles of Lymphoma-associated Hemophagocytic Syndrome: A Comparative Analysis of B-Cell and T-Cell/Natural Killer Cell Lymphomas

To elucidate the differences in pathogenesis between lymphoma-associated hemophagocytic syndromes (LAHS) of theT-cell/ natural killer cell (T/NK) and B-cell (B) types,we comparatively analyzed the clinical features and serum cytokine profiles of 33 patients with LAHS registered in the Kyoto University Hematology/Oncology Study Group.The serum cytokine levels of each patient group (B-LAHS versusT/NK-LAHS) were expressed as the ratio of the median to the upper normal values of the respective cytokines and were as follows: 19.05 versus 13.99 for soluble interleukin 2 (IL-2) receptor, 0.67 versus 0.67 for granulocytemacrophage colony-stimulating factor (GM-CSF), 0.64 versus 1.26 for G-CSF, 5.70 versus 3.61 for M-CSF, 1.54 versus 3.39 for interferon γ (IFN-γ), 13.17 versus 1.17 for IL-6, 6.88 versus 1.58 for tumor necrosis factor α (TNF-α), 0.71 versus 0.41 for IL-1, 1.99 versus 0.21 for IL-12, and 105.32 versus 29.65 for IL-10.The serum levels of IL-6,TNF-α, and IL-10 were significantly higher in the B-LAHS group,whereas those of IFN-γ were significantly lower. These differences between the 2 groups may reflect a difference in the pathogenesis. Higher serum levels of IL-6, TNF-α, and IL-10 may be derived at least partly from neoplastic B-cells themselves. In addition, the extremely high serum levels of IL-10 suggest that a compensatory anti-inflammatory process may operate in both groups and give rise to a profound immunosuppressive state and a poor outcome.

SERUM LEVELS OF SOLUBLE INTERLEUKIN 2 RECEPTOR IN PATIENTS WITH NON-HAEMATOLOGICAL DISORDERS

Recently Pizzolo et d (1987) reported the elevation of soluble Interleukii 2 Receptor (sIL 2R) levels in haematological disorders, i.e. hairy cell leukaemia, Hodgkin’s disease, nonHodgkin’s lymphoma, B-chronic lymphocytic leukaemia, etc. They described that the increase of sIL 2R levels is not diseasespecific but it can be clinically useful as a index of disease activity in a number of haematological disorders. They found no obvious increase of sIL 2R levels in most non-haematological malignancies. We have examined serum sIL 2R levels in a number of nonhaematological disorders (Table I). sIL 2R values were determined using the enzyme-linked immunosorbent assay (Cellfreem interleukin-2 receptor kit, T cell Sciences, Inc., Cambridge, Mass.), based on the use of two monoclonal antibodies (2R1.2 and 7G7/B6) developed against two different epitopes of the IL 2R molecules (MacKeen et al, 1986). Serum levels of sIL 2R were expressed in Units/ml (U/ml) relative to a set of standards supplied with the test kit which Pizzolo’s group also used (Chilosi et al. 1987). In 29 patients with chronic renal failure, the levels of sIL 2R were significantly higher than those seen in normal controls. These patients had received the haemodialysis twice or three times a week and had high levels of urea nitrogen in the blood (BUN= 80.9 f 22.4 mg/dl, meanf SD) before the haemodialysis. No significant decrease of sIL 2R values was found after the haemodialysis. Sixteen patients with non-haematological malignancies, including seven gastric cancer, three colon cancer, three lung cancer and others, also showed high serum levels of sIL 2R. Furthermore, elevated serum sIL 2R values were found in infection. Sixteen patients with infectious disease, including eight viral disease and eight bacterial disease, revealed elevated sIL 2R values. The very high sIL 2R values (up to 50000 U/ml) as observed in adult T-cell leukaemia (Yasuda et al, 1988) or hairy cell leukaemia (Pizzolo et aJ, 198 7) were not detected in our series of the patients with non-haematological disorders. However, in the remission state or the smouldering cases of haematological disorders (Table I), their levels of sIL 2R are very close to those seen in our cases. Our &dings suggest that sIL 2R levels may vary not only with disease activity of haematological disorders but also with the renal function and the presence of infection and non-haematological malignancies. Hence, when serum sIL 2R values might be used as a index of disease activity of haematological disorders, one should rule out the influences from these factors.

Nucleolus-associated J chains in myeloma cells: Clinical significance

Bone marrow aspirates from 20 patients with multiple myeloma (MM), 4 with smoldering multiple myeloma (S‐MM), 1 with idiopathic Bence Jones proteinuria (I‐BJP), and 6 with primary macroglobulinemia (PMG) were examined for nucleolus‐associated J chain. The incidence of nucleolar J chain‐positive (J +) cells among nucleolated cells producing M‐component was measured. This incidence (94.0–100%) in terminal MM was significantly higher than that (0–58.0%) in non‐terminal MM. Judging from a low incidence in the remission phase, chemotherapy might cause a selective elimination of less differentiated myeloma cells with J + nucleoli and might have some effect on J chain synthesis. The incidence of nucleolar J+ cells was very low in S‐MM. The IgM cells in PMG, where J chain is present in a disulfide‐linked form, had no or few J+ nucleoli. No correlation between the incidence of nucleolar J + cells among nucleolated plasma cells and the percentage of nucleolated cells or that of J + cells was found. Large J + nucleoli seemed to be another morphological feature indicating anaplastic myeloma cells. A high incidence of nucleolar J + cells may be one of the indicators for progressive disease.

A case of Gaucher's disease complicated with liver failure.

本邦では遭遇する機会の少ないロシア系ユダヤ人の成人型Gaucher病を経験した.症例は46才男性. 6才時脾摘.全身倦怠感,黄疸にて入院.検査で肝障害著明.アンモニア値508μg/dlと著増.酸フォスファターゼ42.7Uと高値, IgM-HA抗体陽性.意識障害進行し死亡.剖検時の骨髄スタンプ標本でGaucher細胞を多数認めた.肝4700gと腫大し, Gaucher細胞が高度に増生していた.剖検肝の分析では,全脂質の増加あり,薄層クロマトグラフィーでglucocerebrosideが全脂質の87%と著増していた.また人工基質で測定したβ-glucosidase活性は15.4%と低下していた.したがって,本症例は, Gaucher病による肝障害にA型肝炎が合併し,肝不全にて死亡したと考えられた.