Mycobacterium leprae-induced demyelination: a model for early nerve degeneration.

The molecular events that occur at the early phase of many demyelinating neurodegenerative diseases are unknown. A recent demonstration of rapid demyelination and axonal injury induced by Mycobacterium leprae provides a model for elucidating the molecular events of early nerve degeneration which might be common to neurodegenerative diseases of both infectious origin and unknown etiology. The identification of the M. leprae-targeted Schwann cell receptor, dystroglycan, and its associated molecules in myelination, demyelination and axonal functions suggests a role for these molecules in early nerve degeneration.

Thalidomide prolongs experimental autoimmune neuritis in Lewis rats.

Thalidomide is reported to have immunomodulatory and anti-inflammatory effects, which have led to its use in the treatment of a number of immune-mediated disorders, including leprosy, discoid lupus and Behcet's disease, and to prevent immunological rejection phenomena following skin and bone marrow grafts. Experimental autoimmune neuritis (EAN) is a CD4+ T-cell-mediated demyelinating autoimmune disease, which represents an animal model for the study of the immunopathogenesis and immunotherapy of Guillain-Barré syndrome (GBS) in humans. We examined the effect of thalidomide in Lewis rats with EAN, which was induced by immunization with bovine peripheral nerve myelin (BPM) and complete Freund's adjuvant (CFA). Thalidomide prolonged clinical EAN when given at a dose of 200 mg/kg/day by gavage. This clinical effect was associated with increased numbers of inflammatory cells in sciatic nerve sections and elevated numbers of interferon-gamma (IFN-gamma) mRNA-expressing cells among lymph node mononuclear cells from thalidomide-treated EAN rats on day 17 postimmunization, i.e. at the peak of clinical EAN. The finding that thalidomide prolongs clinical EAN is in agreement with the clinical polyneuropathy reported in patients receiving treatment with thalidomide and limits its clinical usefulness.

Characterization of the anti-neural antibodies in the sera of leprosy patients.

Sera from 43 leprosy patients were tested for antibodies that bound to normal human nerve. Thirty-eight percent showed positive staining as demonstrated by indirect immunofluorescence. Only 1 out of 30 control sera tested displayed similar staining. Western blots of myelin and neural intermediate filament (IF) proteins were tested with patient sera. Two of the anti-neural antibody (ANeAb)-positive leprosy sera bound to the P0 protein of PNS myelin. All 17 ANeAb-positive leprosy sera displayed 2 or more bands in the molecular weight range of Mr 45 000-55 000, when tested against IF proteins. One explanation for these findings is that leprosy patients produce antibodies to intermediate filament (IF) proteins released subsequent to the bacterial invasion of the peripheral nerves. The importance of these autoantibodies in the pathogenesis of leprosy is discussed.