Myasthenic crisis with delayed recovery after plasmapheresis.

We report on 2 elderly patients with myasthenia gravis in whom recovery from crisis was prolonged despite intensive plasmapheresis (PP). In both patients, the anti-acetylcholine (anti-AChR) titer failed to fall sufficiently after completing PP. These patients might have had antibodies that produced a more pronounced effect on the degradation of AChR, or the synthesis of AChR might have been reduced by aging. The anti-AChR titer did not correlate with a reduction of IgG after PP in 1 patient. Successful treatment was achieved by keeping the anti-AChR titer at a low level via the concomitant use of prednisolone with PP.

Treatment of experimental allergic encephalomyelitis by selective removal of CD4+ T cells.

Experimental allergic encephalomyelitis (EAE) is a major animal model of human multiple sclerosis (MS). The pathogenesis of both MS and EAE directly involves CD4+ helper T cells. To remove CD4+ T cells selectively from the circulation, we designed a new column in which anti-CD4 monoclonal antibody was immobilized on the activated substance. Most of the CD4+ T cells, including pathogenic T cells, were selectively adsorbed from whole blood with a direct perfusion through the column in vitro, resulting in depletion of the antigen-specific T cell responses. A preliminary trial of ex vivo treatment with the column in EAE rats lowered the percentages of CD4+ populations but failed to alter the course of the disease, suggesting repeated treatment would be necessary to suppress the development of the disease. We conclude that this new column is potentially useful, and repeated treatment would be beneficial in MS and other CD4+ T cell dependent autoimmune diseases.

'Split tolerance' induction by intrathymic injection of acetylcholine receptor in a rat model of autoimmune myasthenia gravis; implications for the design of specific immunotherapies.

Experimental autoimmune myasthenia gravis (EAMG) in the Lewis rat, induced by a single injection of acetylcholine receptor (AChR) protein, is a model used to study human myasthenia gravis (MG). The production of anti-AChR antibodies in the animal model and human MG is T cell-dependent, and AChR-specific T cells have been considered as a potential target for specific immunotherapy. Intrathymic injection of antigens induces antigen-specific tolerance in several T cell-mediated autoimmune models. We examined the effect of intrathymic injection of AChR on T cell responses and the production of antibodies to AChR in EAMG rats. Primed lymph node cells from rats receiving intrathymic injection of AChR exhibited reduced proliferation to AChR with marked suppression of interferon-gamma (IFN-gamma) secretion in the antigen-stimulated culture, compared with those of rats injected with PBS. However, neither anti-Narke AChR nor anti-rat AChR antibody production was suppressed or enhanced in intrathymically AChR-injected animals compared with that of animals injected intrathymically with PBS or perithymically with AChR. This 'split tolerance' may be attributable to the suppression of type-1 T helper cells (Th1). Our results suggest that the suppression of Th1 function alone may not be sufficient for the prevention of antibody-mediated autoimmune diseases.

[Effects of polychlorinated biphenyls on regeneration of the peripheral nerve in rats].

The sciatic nerves was crushed at the mid-thigh level on the last day of 32 days oral administration of PCB. Nerve specimens were obtained from the crushed regions at 1, 2, 4 and 8 weeks after crushing. There was no significant difference between the experimental group and the control group in the density of regenerating fibers and distribution of fiber diameters at 1 and 2 weeks. At 4 and 8 weeks, however, the density of myelinated fibers was higher in the experimental group than in the control group. These results indicate that PCB may inhibit the regeneration of the crushed nerves. It is, however, still unknown that this adverse effects of PCB on the peripheral nerve depends on the disturbance of the remyelination or regeneration of the axon or both.