We describe a case of multiple sclerosis characterized by deposition of immunoglobulin and complement in the areas of active demyelination. This was particularly evident for the C9neo antigen, which is a marker for the activated lytic complement complex and was exclusively deposited in the areas of active myelin destruction. In addition, macrophages in the lesions contained degradation products that were immunoreactive for myelin antigens, immunoglobulins, and C9neo antigen. Destruction of myelin sheaths was associated with incomplete loss of oligodendrocytes in the active areas and reappearance of oligodendrocytes with remyelination in the inactive plaque center. Patient and Methods PatientThe patient was a 47-year-old woman with unremarkable family history. At 15 years of age she had an episode of diplopia and strabismus and bilateral extensor plantar reflexes were observed. A similar transient episode occurred in the subsequent year, and a diagnosis of MS was entertained. At age 28, her vision deteriorated and her gait was described as spastic and atactic. During pregnancy, at age 29, she developed spastic paraparesis and generalized sensory deficiency below T6-7, as well as urinary incontinency. Her optic discs were pale, and her cerebrospinal fluid (CSF) protein concentration was moderately elevated. After treatment with adrenocorticotropic hormone (ACTH) her condition improved and she had a stable remission of the disease for 18 years.At age 47, after an upper respiratory tract infection, her condition suddenly worsened, with abrupt onset of severe paralysis of the left upper extremity. In addition, the patient From the

A panel of 13 monoclonal antibodies (mAbs) sive demyelination is associated with meningeal and perivascular infiltrates of inflammatory cells, parenchymal edema, and blood-brain barrier (BBB) dysfunction.23 The development of this demyelinating pathology is dependent on synergy between T-cell and B-cell responses to myelin autoantigens,45 the effector mechanisms most clearly analyzed in the Lewis rat. In this species the inflammatory aspect of EAE is initiated by an autoimmune T-cell response to myelin antigens, in particular myelin basic protein (MBP).6 The passive transfer of MBP-specific T cells induces an acute inflammatory response in the CNS, associated with an increased permeability of the BBB to serum proteins, but minimal demyelination.7 Extensive primary demyelination in this model is completely dependent on the presence of an antibody response to determinants exposed at the surface of the myelin sheath at the time that the inflammatory response disturbs BBB function. This was formally demonstrated in a cotransfer model in which rats with T-cell-mediated EAE were injected intravenously with the myelin oligodendrocyte glycoprotein (MOG)-specific monoclonal antibody (mAb) 8-18C5.a This mAb recognizes an epitope of MOG that is exposed at the outermost surface of the myelin sheath8 and exhibits complement-dependent demyelinating activity in vitro.9 Normally, circulating antibody is excluded from the CNS by the BBB and is therefore not pathogenic. However, in rats with EAE the mAb can penetrate into the CNS and initiate extensive demyelination, producing lesions similar to those seen in multiple sclerosis.The involvement of complement-dependent mechanisms in the pathogenesis of both MBP-mediated EAE and in antibody-mediated demyelination has been noted in several studies,10-13 and antibodymediated demyelination has been associated with the deposition of granular deposits of C9, indicative of membrane attack complex (MAC) formation.14 However, in vivo complement depletion studies suggest that the MAC is not essential to the pathogenesis of demyelination;10 the major effector mechanism resposible for antibody-mediated demyelination in vivo is a macrophage-mediated antibody-dependent cellmediated cytotoxicity (ADCC) response 15,16

The neuropathology of demyelinating lesions in multiple sclerosis was studied in specimens obtained by diagnostic needle biopsy during early stages of the disease. The lesions were characterized by a chronic inflammatory reaction dominated by lymphocytes and macrophages, plaque-like demyelination, and astroglial sclerosis. Oligodendrocytes within the lesions were studied by immunocytochemistry using antibodies against various myelin and oligodendroglia components. The expression of messenger RNA for proteolipid protein was determined by in situ hybridization. Our studies revealed that myelin-oligodendrocyte glycoprotein is a sensitive and reliable marker for identification of oligodendrocytes in demyelinated plaques. The results suggest that in the early course of the disease in some patients, oligodendrocytes may largely be preserved, whereas in others oligodendroglial loss is pronounced. Loss of oligodendrocytes was only marginally related to the stage of demyelinating activity within the lesions. These findings indicate that the pathogenesis of demyelination may vary within different multiple sclerosis patients.

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Introduction Mucin 1 (MUC1) is a high molecular weight glycoprotein overexpressed on adenocarcinoma cells and is a target for immunotherapy protocols. To date, clinical trials against MUC1 have included advanced cancer patients. Herein, we report a trial using early stage breast cancer patients and injection of oxidized mannan-MUC1.

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