IgM lambda monoclonal antibodies in two patients with motor neuron disease showed the same unique antigenic specificity. They bound to gangliosides GM1 and GD1b and to lacto-N-tetraose-BSA. By immunofluorescence microscopy they bound to central and peripheral nerve tissue and to motor end-plates at the neuromuscular junction. Sera from control subjects did not contain antibodies of similar specificity. Monoclonal IgMs with the same unique specificity could be responsible for motor neuron disease in some patients with monoclonal gammopathies.

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An assessment of the prophylactic and ameliorative effects of deoxyspergualin (NKT-01), an immunosuppressive agent, was carried out in male MRL/MpJ-lpr/lpr (MRL/1) mice which spontaneously develop lupus-like lesions. When NKT-01 was administered ip daily from the age of either 8 or 19 weeks, diseases such as massive lymphadenopathy, circulating anti-DNA antibody and lupus nephritis were markedly suppressed. The primary response to lipopolysaccharide was significantly reduced in MRL/1mice administered NKT-01but the response to sheep red blood cells was not affected. The ability of spleen cells to release interleukins 2 and 3 with or without mitogen was significantly enhanced in mice receiving NKT-01.These findings demonstrate that NKT-01has therapeutic activity against the development of spontaneous disease in MRL/1 mice. 1253Deoxyspergualin (NKT-01) is a derivative of spergualin, a metabolite of Bacillus laterosporusD shown to have immunosuppressive activities in rodents2). This derivative, with a molecular weight of 496.9 and a moiety bearing a spermidine and a guanidinic group, has been found to suppress antibody production and delayed-type hypersensitivity to sheep red blood cells (SRBC) and to have a stronger activity than spergualin in inhibiting the rejection of skin allografts in rats3). In mice, NKT-01 inhibits the development of graft-versus-host disease43. In rats, NKT-01 inhibits the rejection of heart5), liver6), kidney7) and pancreas8) allografts. The purpose of the present study is to examine whether NKT-01can prevent the spontaneous development of autoimmune disease and affect the immune response, when administered to male MRL/MpJ-lpr/lpr (MRL/1) mice. Materials and Methods AnimalsMale MRL/1and MRL/MpJ-+/-f (MRL/+) mice were purchased from Jackson Laboratories, Bar Harbor, U.S.A. Treatment NKT-01 was supplied by Takara Shuzo Co., Ltd., dissolved in saline and sterilized by passing through a 0.22-/mi filter. In a previous experiment, when NKT-01was administered ip daily at an immunosuppressive dose of 3 mg/kg from week 12, weight loss was observed about 6 weeks after the initial administration of NKT-01. Therefore, the dose was lowered to 1.5 mg/kg in all experiments.

Deoxyspergualin (DGS) is a new immunosuppressant which has shown inhibitory haemopoietic activity. We investigated the myeloprotective effect of DSG against the haemopoietic injury of mitomycin C (MMC) or cyclophosphamide (CYC) by measuring peripheral blood cell numbers in dogs. DSG given at 5 mg/kg on days 3, 2 and 1 before, or at 10 mg/kg on either days 2 and 1 before or on day 1 before and the day of injection of MMC at 0.25 mg/kg ameliorated both the thrombocytopenia and leucopenia caused by MMC. This ameliorative effect was more evident on platelet counts than on white blood cell counts. In addition, the leucopenia and thrombocytopenia induced by a single injection of CYC at 10 mg/kg was also ameliorated by prior DSG administration. These findings suggest that DSG may be useful in protecting against the haemopoietic damage induced by chemotherapeutic agents in the treatment of cancer.